Trial Outcomes & Findings for Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers (NCT NCT04430738)

Last Updated: 2025-12-11

Results Overview

A renal DLT was defined as an increase in serum cystatin C \>1.5\* baseline that was not related to pre-renal or post-renal etiologies (including disease progression, dehydration and intercurrent illness) and occurred during the period of treatment with tucatinib in combination with trastuzumab and FOLFOX between the first dose of tucatinib and the end of Cycle 3. Increased serum cystatin C for which there was an alternative clinical explanation (eg, clearly related to an intercurrent illness or disease progression) was not considered renal DLTs.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

From first dose of tucatinib until end of Cycle 3 (up to 42 days)

Results posted on

2025-12-11

Participant Flow

Participants diagnosed with unresectable or metastatic human epidermal growth factor receptor 2 positive (HER2+) gastrointestinal (GI) cancer were enrolled across Japan and the United States.

The study consisted of two phases: phase 1b (dose escalation) consisting of cohorts 1A, 1B, 1D, 1E and 1F and phase 2 (dose expansion) consisting of Cohort 2B. Cohorts 1C and 1G (Phase 1b) and Cohort 2A (Phase 2) were also planned; however, sponsor decided to close the enrollment before these cohorts were opened, therefore no data is reported for Cohorts 1C, 1G and 2A in any section of the results. Data is reported at the primary completion date.

Participant milestones

Participant milestones
Measure	Cohort 1A Participants received tucatinib 150 milligrams (mg) orally (PO) twice daily (BID) on Days 1 to 14, loading dose of trastuzumab at 6 milligram per kilogram (mg/kg) via intravenous (IV) infusion on Day 1 of Cycle 1 followed by 4 mg/kg once every 2 weeks (Q2W) starting on Cycle 2 Day 1 and mFOLFOX 6 or mFOLFOX7 (oxaliplatin 85 milligram per meter square (mg/m\^2) IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until disease progression (PD), unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1D Japanese participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1E Participants received tucatinib 300 mg PO BID on Days 1 to 14 (Each cycle = 14 Days), trastuzumab every three weeks (Q3W) 8 mg/kg via IV infusion on Day 1 of Cycle 1 and then 6 mg/kg every 3 weeks (Q3W) starting on Day 1 of Cycle 2 (Each cycle = 21 Days), mFOLFOX 6 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle (Each cycle = 14 Days) and pembrolizumab 400 mg IV on Day 1 of Cycle 1 and then every six weeks (Q6W) starting on Day 1 of Cycle2 (Each cycle = 42 days). Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1F Participants received tucatinib 300 mg PO BID on Days 1 to 14, trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 6 mg/kg Q3W starting on Day 1 of Cycle 2 (Each cycle = 21 days), CAPOX (oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000mg/m\^2 PO BID on evening of Day 1 to morning of Day 15 of Cycle 1 and Day 1 to 14 of each subsequent cycle) (Each cycle = 21 Days) and pembrolizumab 400 mg IV on Day 1 of Cycle 1 and then Q6W starting on Day 1 of Cycle 2. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 2B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 8 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 6 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Phase 1: Dose Escalation STARTED	5	11	7	4	8	0
Phase 1: Dose Escalation COMPLETED	3	4	0	0	0	0
Phase 1: Dose Escalation NOT COMPLETED	2	7	7	4	8	0
Phase 1: Dose Expansion STARTED	0	0	0	0	0	5
Phase 1: Dose Expansion COMPLETED	0	0	0	0	0	0
Phase 1: Dose Expansion NOT COMPLETED	0	0	0	0	0	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1A Participants received tucatinib 150 milligrams (mg) orally (PO) twice daily (BID) on Days 1 to 14, loading dose of trastuzumab at 6 milligram per kilogram (mg/kg) via intravenous (IV) infusion on Day 1 of Cycle 1 followed by 4 mg/kg once every 2 weeks (Q2W) starting on Cycle 2 Day 1 and mFOLFOX 6 or mFOLFOX7 (oxaliplatin 85 milligram per meter square (mg/m\^2) IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until disease progression (PD), unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1D Japanese participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1E Participants received tucatinib 300 mg PO BID on Days 1 to 14 (Each cycle = 14 Days), trastuzumab every three weeks (Q3W) 8 mg/kg via IV infusion on Day 1 of Cycle 1 and then 6 mg/kg every 3 weeks (Q3W) starting on Day 1 of Cycle 2 (Each cycle = 21 Days), mFOLFOX 6 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle (Each cycle = 14 Days) and pembrolizumab 400 mg IV on Day 1 of Cycle 1 and then every six weeks (Q6W) starting on Day 1 of Cycle2 (Each cycle = 42 days). Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1F Participants received tucatinib 300 mg PO BID on Days 1 to 14, trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 6 mg/kg Q3W starting on Day 1 of Cycle 2 (Each cycle = 21 days), CAPOX (oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000mg/m\^2 PO BID on evening of Day 1 to morning of Day 15 of Cycle 1 and Day 1 to 14 of each subsequent cycle) (Each cycle = 21 Days) and pembrolizumab 400 mg IV on Day 1 of Cycle 1 and then Q6W starting on Day 1 of Cycle 2. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 2B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 8 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 6 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Phase 1: Dose Escalation Death	1	4	4	1	6	0
Phase 1: Dose Escalation Participation terminated by sponsor	0	2	3	2	2	0
Phase 1: Dose Escalation Continuing to long term extension phase (LTEP)	0	1	0	1	0	0
Phase 1: Dose Escalation Other	1	0	0	0	0	0
Phase 1: Dose Expansion Participation terminated by sponsor	0	0	0	0	0	3
Phase 1: Dose Expansion Continuing to LTEP	0	0	0	0	0	2

Baseline Characteristics

Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=11 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1D n=7 Participants Japanese participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1E n=4 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14 (Each cycle = 14 Days), trastuzumab every three weeks (Q3W) 8 mg/kg via IV infusion on Day 1 of Cycle 1 and then 6 mg/kg every 3 weeks (Q3W) starting on Day 1 of Cycle 2 (Each cycle = 21 Days), mFOLFOX 6 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle (Each cycle = 14 Days) and pembrolizumab 400 mg IV on Day 1 of Cycle 1 and then every six weeks (Q6W) starting on Day 1 of Cycle2 (Each cycle = 42 days). Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1F n=8 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 6 mg/kg Q3W starting on Day 1 of Cycle 2 (Each cycle = 21 days), CAPOX (oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000mg/m\^2 PO BID on evening of Day 1 to morning of Day 15 of Cycle 1 and Day 1 to 14 of each subsequent cycle) (Each cycle = 21 Days) and pembrolizumab 400 mg IV on Day 1 of Cycle 1 and then Q6W starting on Day 1 of Cycle 2. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 2B n=5 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 8 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 6 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Total n=40 Participants Total of all reporting groups
Age, Continuous	49.4 years STANDARD_DEVIATION 11.7 • n=237 Participants	65.4 years STANDARD_DEVIATION 12.9 • n=243 Participants	61.6 years STANDARD_DEVIATION 11.8 • n=480 Participants	65.8 years STANDARD_DEVIATION 6.3 • n=639 Participants	56.5 years STANDARD_DEVIATION 17.3 • n=277 Participants	60.6 years STANDARD_DEVIATION 8.4 • n=294 Participants	60.4 years STANDARD_DEVIATION 13.1 • n=3238 Participants
Sex: Female, Male Female	1 Participants n=237 Participants	3 Participants n=243 Participants	5 Participants n=480 Participants	1 Participants n=639 Participants	2 Participants n=277 Participants	3 Participants n=294 Participants	15 Participants n=3238 Participants
Sex: Female, Male Male	4 Participants n=237 Participants	8 Participants n=243 Participants	2 Participants n=480 Participants	3 Participants n=639 Participants	6 Participants n=277 Participants	2 Participants n=294 Participants	25 Participants n=3238 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=237 Participants	0 Participants n=243 Participants	0 Participants n=480 Participants	0 Participants n=639 Participants	0 Participants n=277 Participants	0 Participants n=294 Participants	0 Participants n=3238 Participants
Race (NIH/OMB) Asian	0 Participants n=237 Participants	0 Participants n=243 Participants	7 Participants n=480 Participants	2 Participants n=639 Participants	7 Participants n=277 Participants	3 Participants n=294 Participants	19 Participants n=3238 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=237 Participants	0 Participants n=243 Participants	0 Participants n=480 Participants	0 Participants n=639 Participants	0 Participants n=277 Participants	0 Participants n=294 Participants	0 Participants n=3238 Participants
Race (NIH/OMB) Black or African American	0 Participants n=237 Participants	1 Participants n=243 Participants	0 Participants n=480 Participants	0 Participants n=639 Participants	0 Participants n=277 Participants	0 Participants n=294 Participants	1 Participants n=3238 Participants
Race (NIH/OMB) White	5 Participants n=237 Participants	9 Participants n=243 Participants	0 Participants n=480 Participants	2 Participants n=639 Participants	1 Participants n=277 Participants	2 Participants n=294 Participants	19 Participants n=3238 Participants
Race (NIH/OMB) More than one race	0 Participants n=237 Participants	1 Participants n=243 Participants	0 Participants n=480 Participants	0 Participants n=639 Participants	0 Participants n=277 Participants	0 Participants n=294 Participants	1 Participants n=3238 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=237 Participants	0 Participants n=243 Participants	0 Participants n=480 Participants	0 Participants n=639 Participants	0 Participants n=277 Participants	0 Participants n=294 Participants	0 Participants n=3238 Participants
Race/Ethnicity, Customized Not Hispanic, Latino/a, or of Spanish Origin	5 Participants n=237 Participants	10 Participants n=243 Participants	7 Participants n=480 Participants	4 Participants n=639 Participants	8 Participants n=277 Participants	5 Participants n=294 Participants	39 Participants n=3238 Participants
Race/Ethnicity, Customized Not reportable	0 Participants n=237 Participants	1 Participants n=243 Participants	0 Participants n=480 Participants	0 Participants n=639 Participants	0 Participants n=277 Participants	0 Participants n=294 Participants	1 Participants n=3238 Participants

PRIMARY outcome

Timeframe: From first dose of tucatinib until end of Cycle 3 (up to 42 days)

Population: The DLT-evaluable analysis set for cohort 1A and 1B included all participants in cohort 1A or 1B who met one of the following criteria: had a renal DLT or had taken at least 75% of planned oxaliplatin and tucatinib doses per cycle and were followed for at least 2 cycles of study treatment (through the end of Cycle 3 for FOLFOX regimens), inclusive of dose delays.

Outcome measures

Outcome measures
Measure	Cohort 1A n=3 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=8 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Renal Dose-Limiting Toxicities (DLTs): Phase 1b (Cohort 1A and 1B)	0 Participants	1 Participants

PRIMARY outcome

Timeframe: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=8 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Treatment Emergent Adverse Events (TEAEs): Phase 1b (Cohort 1E and 1F)	4 Participants	8 Participants

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment. Treatment related TEAEs were AEs related to any study treatment and relatedness was judged by investigator.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=8 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Treatment Related TEAEs: Phase 1b (Cohort 1E and 1F)	4 Participants	8 Participants

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment. TEAEs were graded according to National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v) 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Number of participants with \>= grade 3 TEAEs are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=8 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Greater Than or Equal to (>=) Grade 3 TEAEs: Phase 1b (Cohort 1E and 1F)	4 Participants	7 Participants

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator. Number of participants with \>= grade 3 treatment related TEAEs are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=8 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With >= Grade 3 Treatment Related TEAEs: Phase 1b (Cohort 1E and 1F)	4 Participants	7 Participants

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=8 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Any Serious Adverse Event (SAE): Phase 1b (Cohort 1E and 1F)	1 Participants	6 Participants

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=8 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Any Treatment Related SAE: Phase 1b (Cohort 1E and 1F)	1 Participants	5 Participants

PRIMARY outcome

Timeframe: Cycle 1 (Up to 21 days)

Population: The DLT evaluable analysis set for cohort 1E included all participants who met one of following criteria: had a DLT or had taken at least 75% of planned study treatment for first 21 days of study treatment and were followed for at least 21 days of study treatment.

DLTs were AEs/ laboratory abnormalities that were considered to be related to tucatinib/ tucatinib in combination with chemotherapy(mFOLFOX6/CAPOX) and/or trastuzumab and/or pembrolizumab. DLTs was defined any of following: a-)Hepatic- any instance of aspartate aminotransferase(AST)/ alanine aminotransferase(ALT)\>3\*upper limit of normal(ULN) and total bilirubin \>2\*ULN that is not thought to be due to progressive disease(PD)/other medical illness. PD:at least 20% increase in sum of diameters of target lesions,taking as reference smallest sum on study. In addition to relative increase of 20%,sum must also demonstrate an absolute increase of at least 5 millimeters(mm). b-) Non-hematologic- any clinically significant, non-hematologic treatment-related AE\>= grade(G)3, with following exceptions:G3 fatigue=\< 7days,G3 diarrhea,nausea/vomiting without optimal use of anti-emetics/antidiarrheals c-)hematologic:\>=G3 febrile neutropenia and absolute neutrophil count(ANC) decreased G4 for \>7days.

Outcome measures

Outcome measures
Measure	Cohort 1A n=3 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With DLTs: Phase 1b (Cohort 1E)	1 Participants	—

PRIMARY outcome

Timeframe: Cycle 1 (Up to 28 days)

Population: The DLT evaluable analysis set for cohort 1F included all participants who met one of following criteria: had a DLT or had taken at least 75% of planned study treatment for first 28 days of study treatment and were followed for at least 28 days of study treatment.

DLTs were AEs/ laboratory abnormalities that were considered to be related to tucatinib/ tucatinib in combination with chemotherapy (mFOLFOX6/CAPOX) and/ or trastuzumab and/ or pembrolizumab. DLTs was defined any of following: a-) Hepatic- any instance of AST/ ALT \>3\*ULN and total bilirubin \>2\*ULN that is not thought to be due to PD/ other medical illness. PD: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. b-) Non-hematologic- any clinically significant, non-hematologic treatment-related AE\>= grade 3, with following exceptions: grade 3 fatigue=\< 7days, grade 3 diarrhea, nausea/vomiting without optimal use of anti-emetics/antidiarrheals c-) hematologic: \>= grade 3 febrile neutropenia and ANC decreased grade 4 for \>7days.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With DLTs: Phase 1b (Cohort 1F)	0 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

The following hematological parameters were assessed: hemoglobin decreased, leukocytes decreased, lymphocytes decreased, neutrophils decreased and platelets decreased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment. Hematological laboratory abnormalities were graded according to NCI CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with hematological abnormalities of any grade were reported.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=8 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Hemoglobin decreased	2 Participants	7 Participants
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Leukocytes decreased	4 Participants	3 Participants
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Lymphocytes decreased	4 Participants	5 Participants
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Neutrophils decreased	4 Participants	2 Participants
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Platelets decreased	3 Participants	8 Participants

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

The following chemistry laboratory parameters were assessed: alanine aminotransferase (ALT) increased, albumin decreased, alkaline phosphatase increased, aspartate aminotransferase (AST) increased, calcium corrected for albumin decreased, creatinine increased, calcium corrected for albumin increased, lactate dehydrogenase increased, potassium decreased, potassium increased, sodium decreased, sodium increased and total bilirubin increased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment Chemistry laboratory abnormalities were graded according to NCI CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with chemistry abnormalities of any grade were reported.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=8 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) ALT increased	3 Participants	7 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Albumin decreased	2 Participants	5 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Alkaline Phosphatase increased	0 Participants	2 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) AST increased	2 Participants	7 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Calcium Corrected for Albumin decreased	1 Participants	4 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Creatinine increased	1 Participants	3 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Calcium Corrected for Albumin increased	0 Participants	1 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Lactate Dehydrogenase increased	3 Participants	3 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Potassium decreased	4 Participants	5 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Potassium increased	1 Participants	1 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Sodium decreased	3 Participants	6 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Sodium increased	1 Participants	2 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F) Total Bilirubin increased	1 Participants	2 Participants

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Vital signs included temperature, blood pressure, heart rate and respiratory rate. Clinically significant vital signs were defined as: temperature greater than or equal to (\>=) 38 degrees Celsius, respiratory rate greater than (\>) 20 breaths per minute, systolic blood pressure (SBP) \>= 120 millimeter of mercury (mmHg) or diastolic blood pressure (DBP) \>= 80 mmHg, SBP \>= 140 mmHg or DBP \>= 90 mmHg and heart rate \> 100 beats per minute (bpm).

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=8 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1E and 1F) SBP >= 120 mmHg or DBP >= 80 mmHg	4 Participants	8 Participants
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1E and 1F) Temperature >= 38 degrees Celcius	0 Participants	0 Participants
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1E and 1F) Respiratory Rate > 20 breaths per minute	2 Participants	2 Participants
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1E and 1F) SBP >= 140 mmHg or DBP >= 90 mmHg	4 Participants	7 Participants
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1E and 1F) Heart rate > 100 bpm	2 Participants	4 Participants

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=7 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With TEAEs: Phase 1b (Cohort 1D)	7 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=7 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Treatment Related TEAEs: Phase 1b (Cohort 1D)	7 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Number of participants with \>= grade 3 TEAEs are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort 1A n=7 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With >= Grade 3 TEAEs: Phase 1b (Cohort 1D)	7 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator. Number of participants with \>= grade 3 treatment related TEAEs are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort 1A n=7 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With >= Grade 3 Treatment Related TEAEs: Phase 1b (Cohort 1D)	6 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=7 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Any SAE: Phase 1b (Cohort 1D)	3 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=7 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Any Treatment Related SAE: Phase 1b (Cohort 1D)	0 Participants	—

PRIMARY outcome

Timeframe: Cycle 1 (Up to 28 days)

Population: The DLT-evaluable analysis set for Cohort 1D included all participants who met one of the following criteria: had a DLT or had taken at least 75% of planned fluorouracil, oxaliplatin, trastuzumab, and tucatinib doses and were followed for at least 28 days.

DLTs were AEs/ laboratory abnormalities that were considered to be related to tucatinib/ tucatinib in combination with chemotherapy (mFOLFOX6/CAPOX) and/ or trastuzumab and/ or pembrolizumab. DLTs was defined any of following: a-) Hepatic- any instance of AST/ ALT \>3\*ULN and total bilirubin \>2\*ULN that is not thought to be due to PD/ other medical illness. PD: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. b-) Non-hematologic- any clinically significant, non-hematologic treatment-related AE\>= grade 3, with following exceptions: grade 3 fatigue=\< 7days, grade 3 diarrhea, nausea/vomiting without optimal use of anti-emetics/antidiarrheals c-) hematologic: \>= grade 3 febrile neutropenia and ANC decreased grade 4 for \>7days.

Outcome measures

Outcome measures
Measure	Cohort 1A n=6 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With DLTs: Phase 1b (Cohort 1D)	1 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

The following hematological parameters were assessed: hemoglobin decreased, leukocytes decreased, lymphocytes decreased, neutrophils decreased and platelets decreased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Hematological laboratory abnormalities were graded according to NCI CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with hematological abnormalities of any grade were reported.

Outcome measures

Outcome measures
Measure	Cohort 1A n=7 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1D) Hemoglobin decreased	4 Participants	—
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1D) Leukocytes decreased	7 Participants	—
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1D) Lymphocytes decreased	5 Participants	—
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1D) Neutrophils decreased	6 Participants	—
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1D) Platelets decreased	6 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

The following chemistry parameters were assessed: ALT increased, albumin decreased, alkaline phosphatase increased, AST increased, calcium corrected for albumin decreased, creatinine increased, lactate dehydrogenase increased, potassium decreased, potassium increased, sodium decreased and sodium increased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Chemistry laboratory parameters abnormalities were graded according to NCI CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with chemistry abnormalities of any grade were reported.

Outcome measures

Outcome measures
Measure	Cohort 1A n=7 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1D) ALT increased	6 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1D) Albumin decreased	1 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1D) Alkaline Phosphatase increased	3 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1D) AST increased	5 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1D) Calcium Corrected for Albumin decreased	3 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1D) Creatinine increased	5 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1D) Lactate Dehydrogenase increased	2 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1D) Potassium decreased	4 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1D) Potassium increased	1 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1D) Sodium decreased	6 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1D) Sodium increased	1 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Vital signs included temperature, blood pressure, heart rate and respiratory rate. Clinically significant vital signs were defined as: temperature \>= 38 degrees Celsius, respiratory rate \> 20 breaths per minute, SBP \>= 120 mmHg or DBP \>= 80 mmHg, SBP \>= 140 mmHg or DBP \>= 90 mmHg and heart rate \> 100 beats per minute (bpm).

Outcome measures

Outcome measures
Measure	Cohort 1A n=7 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1D) SBP >= 120 mmHg or DBP >= 80 mmHg	6 Participants	—
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1D) Temperature >= 38C	0 Participants	—
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1D) Respiratory Rate > 20 breaths per minute	2 Participants	—
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1D) SBP >= 140 mmHg or DBP >= 90 mmHg	6 Participants	—
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1D) Heart rate > 100 bpm	2 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

An AE was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Dose hold was considered as dose delay and dose elimination. Number of participants with TEAEs leading to dose holds are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort 1A n=7 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With TEAEs Leading to Dose Holds: Phase 1b (Cohort 1D)	6 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

An AE was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Number of participants with TEAEs leading to dose reductions are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort 1A n=7 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With TEAEs Leading to Dose Reductions: Phase 1b (Cohort 1D)	0 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

An AE was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Number of participants with TEAEs leading to dose discontinuations (i.e. permanent withdrawal of tucatinib, trastuzumab, oxaliplatin, fluorouracil and leucovorin) are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort 1A n=7 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With TEAEs Leading to Dose Discontinuations: Phase 1b (Cohort 1D) Tucatinib	2 Participants	—
Number of Participants With TEAEs Leading to Dose Discontinuations: Phase 1b (Cohort 1D) Trastuzumab	1 Participants	—
Number of Participants With TEAEs Leading to Dose Discontinuations: Phase 1b (Cohort 1D) Oxaliplatin	3 Participants	—
Number of Participants With TEAEs Leading to Dose Discontinuations: Phase 1b (Cohort 1D) Fluorouracil	1 Participants	—
Number of Participants With TEAEs Leading to Dose Discontinuations: Phase 1b (Cohort 1D) Leucovorin	1 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With TEAEs: Phase 2 (Cohort 2B)	5 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Treatment Related TEAEs: Phase 2 (Cohort 2B)	5 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Number of participants with \>= grade 3 TEAEs are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With >= Grade 3 TEAEs: Phase 2 (Cohort 2B)	4 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator. Number of participants with \>= grade 3 treatment related TEAEs are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With >= Grade 3 Treatment Related TEAEs: Phase 2 (Cohort 2B)	3 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Any SAE: Phase 2 (Cohort 2B)	3 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Any Treatment Related SAE: Phase 2 (Cohort 2B)	1 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Following hematological parameters were assessed: hemoglobin decreased, leukocytes decreased, lymphocytes decreased, neutrophils decreased and platelets decreased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Hematological abnormalities were graded according to NCI CTCAE v 5.0; where, grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with hematologic abnormalities of any grade were reported.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 2 (Cohort 2B) Hemoglobin decreased	2 Participants	—
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 2 (Cohort 2B) Leukocytes decreased	3 Participants	—
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 2 (Cohort 2B) Lymphocytes decreased	2 Participants	—
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 2 (Cohort 2B) Neutrophils decreased	4 Participants	—
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 2 (Cohort 2B) Platelets decreased	5 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.

Following chemistry parameters were assessed: ALT increased, albumin decreased, alkaline phosphatase increased, AST increased, creatinine increased, glomerular filtration rate (GFR) estimated decreased, lactate dehydrogenase increased, potassium decreased, potassium increased, sodium decreased, sodium increased and total bilirubin increased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Chemistry abnormalities were graded according to NCI CTCAE v 5.0; where, grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Participants with chemistry abnormalities of any grade were reported.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 2 (Cohort 2B) ALT increased	4 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 2 (Cohort 2B) Albumin decreased	3 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 2 (Cohort 2B) Alkaline phosphatase increased	1 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 2 (Cohort 2B) AST increased	3 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 2 (Cohort 2B) Creatinine increased	3 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 2 (Cohort 2B) GFR, estimated decreased	1 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 2 (Cohort 2B) Lactate dehydrogenase increased	1 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 2 (Cohort 2B) Potassium decreased	3 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 2 (Cohort 2B) Potassium increased	2 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 2 (Cohort 2B) Sodium decreased	2 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 2 (Cohort 2B) Sodium increased	1 Participants	—
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 2 (Cohort 2B) Total bilirubin increased	1 Participants	—

PRIMARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Vital signs included temperature, blood pressure and heart rate. Clinically significant vital signs were defined as: temperature \>= 38 degrees Celsius, respiratory rate \> 20 breaths per minute, SBP \>= 120 mmHg or DBP \>= 80 mmHg, SBP \>= 140 mmHg or DBP \>= 90 mmHg and heart rate \> 100 bpm.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 2 (Cohort 2B) Temperature >= 38 degrees Celsius	0 Participants	—
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 2 (Cohort 2B) Respiratory Rate > 20 breaths per minute	1 Participants	—
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 2 (Cohort 2B) SBP >= 120 mmHg or DBP >= 80 mmHg	5 Participants	—
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 2 (Cohort 2B) SBP >= 140 mmHg or DBP >= 90 mmHg	4 Participants	—
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 2 (Cohort 2B) Heart rate > 100 bpm	0 Participants	—

SECONDARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=11 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With TEAEs: Phase 1b (Cohort 1A and 1B)	5 Participants	11 Participants

SECONDARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=11 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Treatment Related TEAEs: Phase 1b (Cohort 1A and 1B)	4 Participants	11 Participants

SECONDARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Number of participants with \>= grade 3 TEAEs are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=11 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With >= Grade 3 TEAEs: Phase 1b (Cohort 1A and 1B)	2 Participants	8 Participants

SECONDARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator. Number of participants with \>= grade 3 treatment related TEAEs are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=11 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With >= Grade 3 Treatment Related TEAEs: Phase 1b (Cohort 1A and 1B)	1 Participants	6 Participants

SECONDARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=11 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Any SAE: Phase 1b (Cohort 1A and 1B)	1 Participants	5 Participants

SECONDARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=11 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Any Treatment Related SAE: Phase 1b (Cohort 1A and 1B)	0 Participants	4 Participants

SECONDARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Following hematological parameters were assessed: hemoglobin decreased, leukocytes decreased, lymphocytes decreased, neutrophils decreased and platelets decreased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Hematological laboratory abnormalities were graded according to NCI CTCAE v 5.0; where, grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Participants with hematological abnormalities of any grade were reported.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=11 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Lymphocytes decreased	0 Participants	8 Participants
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Hemoglobin decreased	1 Participants	5 Participants
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Leukocytes decreased	0 Participants	9 Participants
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Neutrophils decreased	0 Participants	7 Participants
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Platelets decreased	2 Participants	10 Participants

SECONDARY outcome

Following chemistry parameters were assessed: ALT increased, albumin decreased, alkaline phosphatase increased, AST increased, calcium corrected for albumin decreased, calcium corrected for albumin increased, creatinine increased, Cystatin C increased, GFR estimated decreased, lactate dehydrogenase increased, potassium decreased, potassium increased, sodium decreased and total bilirubin increased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Chemistry laboratory abnormalities were graded according to NCI CTCAE v 5.0 grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Participants with chemistry abnormalities of any grade were reported.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=11 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) AST increased	1 Participants	3 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Calcium corrected for albumin decreased	1 Participants	4 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Calcium corrected for albumin increased	0 Participants	1 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Creatinine increased	0 Participants	8 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Cystatin C increased	2 Participants	8 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) GFR estimated decreased	0 Participants	6 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Lactate dehydrogenase increased	1 Participants	4 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Potassium decreased	0 Participants	3 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Potassium increased	0 Participants	1 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Sodium decreased	2 Participants	2 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Total bilirubin increased	0 Participants	2 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) ALT increased	3 Participants	6 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Albumin decreased	2 Participants	3 Participants
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B) Alkaline Phosphatase increased	0 Participants	3 Participants

SECONDARY outcome

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=11 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1A and 1B) Temperature >= 38 degrees Celsius	0 Participants	0 Participants
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1A and 1B) Respiratory Rate > 20 breaths per min	0 Participants	1 Participants
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1A and 1B) SBP >= 120 mmHg or DBP >= 80 mmHg	5 Participants	11 Participants
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1A and 1B) SBP >= 140 mmHg or DBP >= 90 mmHg	1 Participants	9 Participants
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1A and 1B) Heart rate > 100 bpm	0 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline, Cycle 1 Day 3, Cycle 1 Day 8, Cycle 2 Day 1, Cycle 2 Day 3, Cycle 2 Day 8 (each cycle=14 days)

Population: The safety analysis set included all participants who were enrolled in the study and received any amount of study treatment. Here "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.

GFR value was estimated using serum Cystatin C. Baseline was considered as the most recent non-missing measurement prior to the first dose of any study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=11 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Change From Baseline in Glomerular Filtration Rate (GFR): Phase 1b (Cohort 1A and 1B) Baseline	91.1 Milliliter per minute per 1.73 meter^2 Standard Deviation 19.2	87.4 Milliliter per minute per 1.73 meter^2 Standard Deviation 14.6
Change From Baseline in Glomerular Filtration Rate (GFR): Phase 1b (Cohort 1A and 1B) Change at Cycle 1 Day 3	-12.0 Milliliter per minute per 1.73 meter^2 Standard Deviation 10.4	-17.3 Milliliter per minute per 1.73 meter^2 Standard Deviation 7.2
Change From Baseline in Glomerular Filtration Rate (GFR): Phase 1b (Cohort 1A and 1B) Change at Cycle 1 Day 8	2.7 Milliliter per minute per 1.73 meter^2 Standard Deviation 6.5	0.2 Milliliter per minute per 1.73 meter^2 Standard Deviation 11.5
Change From Baseline in Glomerular Filtration Rate (GFR): Phase 1b (Cohort 1A and 1B) Change at Cycle 2 Day 1	3.7 Milliliter per minute per 1.73 meter^2 Standard Deviation 4.6	0.0 Milliliter per minute per 1.73 meter^2 Standard Deviation 13.8
Change From Baseline in Glomerular Filtration Rate (GFR): Phase 1b (Cohort 1A and 1B) Change at Cycle 2 Day 3	-19.3 Milliliter per minute per 1.73 meter^2 Standard Deviation 11.9	-17.0 Milliliter per minute per 1.73 meter^2 Standard Deviation 14.7
Change From Baseline in Glomerular Filtration Rate (GFR): Phase 1b (Cohort 1A and 1B) Change at Cycle 2 Day 8	-4.9 Milliliter per minute per 1.73 meter^2 Standard Deviation 4.1	0.6 Milliliter per minute per 1.73 meter^2 Standard Deviation 14.5

SECONDARY outcome

Timeframe: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2

Population: The pharmacokinetic (PK) analysis set included all participants in the safety set from whom at least one PK assessment was reported. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.

PK parameters were determined using noncompartmental analysis.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=7 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Area Under the Plasma Concentration-Time Curve From 0 to 8 Hours (AUC 0-8h) of Tucatinib at Cycle 1 Day 1: Phase 1b (Cohort 1A and 1B)	1130 Nanogramhours per milliliter (ngh/mL) Geometric Coefficient of Variation 108	1970 Nanogramhours per milliliter (ngh/mL) Geometric Coefficient of Variation 33.5

SECONDARY outcome

Timeframe: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2

Population: The PK analysis set included all participants in the safety set from whom at least one PK assessment was reported. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for the outcome measure.

PK parameters were determined using noncompartmental analysis.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=7 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Maximum Observed Concentration (Cmax) of Tucatinib: Phase 1b (Cohort 1A and 1B)	197 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 105	403 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 42.7

SECONDARY outcome

Timeframe: Predose on Day 1 of Cycle 2

PK parameters were determined using noncompartmental analysis.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=7 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Observed Trough Concentration in Plasma (Ctrough) of Tucatinib: Phase 1b (Cohort 1A and 1B)	106 ng/mL Geometric Coefficient of Variation 113	255 ng/mL Geometric Coefficient of Variation 45.2

SECONDARY outcome

Timeframe: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2

PK parameters were determined using noncompartmental analysis.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=7 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Time at Which the Maximum Plasma Concentration Occurs (Tmax) of Tucatinib: Phase 1b (Cohort 1A and 1B)	3.50 hours Interval 0.95 to 4.2	4.08 hours Interval 1.0 to 7.97

SECONDARY outcome

Timeframe: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2

PK parameters were determined using noncompartmental analysis.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=7 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
AUC 0-8h of Oxaliplatin: Phase 1b (Cohort 1A and 1B) Cycle 2 Day 1	11600 Nanogramhours per milliliter (ngh/mL) Geometric Coefficient of Variation 20.2	12100 Nanogramhours per milliliter (ngh/mL) Geometric Coefficient of Variation 10.2
AUC 0-8h of Oxaliplatin: Phase 1b (Cohort 1A and 1B) Cycle 1 Day 1	10400 Nanogramhours per milliliter (ngh/mL) Geometric Coefficient of Variation 13.5	11200 Nanogramhours per milliliter (ngh/mL) Geometric Coefficient of Variation 22.8

SECONDARY outcome

Timeframe: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2

PK parameters were determined using noncompartmental analysis.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=7 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Cmax of Oxaliplatin: Phase 1b (Cohort 1A and 1B) Cycle 1 Day 1	2200 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 6.42	2240 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 15.4
Cmax of Oxaliplatin: Phase 1b (Cohort 1A and 1B) Cycle 2 Day 1	2250 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 15.7	2350 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 10.9

SECONDARY outcome

Timeframe: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2

PK parameters were determined using noncompartmental analysis.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=7 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Tmax of Oxaliplatin: Phase 1b (Cohort 1A and 1B) Cycle 1 Day 1	2.08 Hours Interval 2.03 to 2.13	2.12 Hours Interval 2.0 to 2.2
Tmax of Oxaliplatin: Phase 1b (Cohort 1A and 1B) Cycle 2 Day 1	2.10 Hours Interval 2.0 to 2.27	2.03 Hours Interval 1.85 to 2.18

SECONDARY outcome

Timeframe: From the first dose of study treatment until the first documented CR or PR or before start of any new anti-cancer therapy (up to 24.1 months)

Population: The response evaluable set included all participants who met all following criteria: had measurable disease at baseline, received any amount of study treatment, and had at least one post-baseline disease assessment or discontinued due to clinical progression, toxicity or death.

ORR was defined as percentage of participants with confirmed complete response (CR)/ partial response (PR) per investigator according to response evaluation criteria in solid tumors version 1.1 (RECIST) v1.1. For response to be considered confirmed, subsequent response had to be at least 4 weeks after initial response. CR: complete disappearance of all target lesions with exception of nodal disease and complete disappearance of non-target lesions and normalization of tumor marker level. Any pathological lymph nodes(whether target/ non-target) must have reduction in short axis to \<10 mm. PR: \>= 30% decrease in sum of diameters of target lesions, taking as reference baseline sum of diameters. 90% exact confidence interval (CI) was based on Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=6 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Objective Response Rate (ORR) Per Investigator (INV): Phase 1b (Cohort 1E and 1F)	100.0 Percentage of Participants Interval 47.3 to 100.0	66.7 Percentage of Participants Interval 27.1 to 93.7

SECONDARY outcome

Timeframe: From the first documented objective response until the first documentation of PD or death due to any cause, whichever occurred first (up to 18.1 months)

DOR was defined as time from first documented objective response (CR or PR that was subsequently confirmed) to first documented PD per RECIST v1.1 or death due to any cause, whichever occurred first. PD: at least a 20 % increase in sum of diameters of target lesions, taking as reference smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. CR: complete disappearance of all target lesions with exception of nodal disease and complete disappearance of non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: a \>= 30 % decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters. 90% exact CI was based on Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=4 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Duration of Response (DOR) Per INV: Phase 1b (Cohort 1E and 1F)	15.5 Months Interval 4.9 to Upper limit of 90% CI could not be estimated due to insufficient number of participants with events	12.4 Months Interval 4.3 to Upper limit of 90% CI could not be estimated due to insufficient number of participants with events

SECONDARY outcome

Timeframe: From the first dose of study treatment until the first documented PD or death from any cause or censoring date, whichever occurred first (up to 24.1 months)

Population: The full analysis set (FAS) included all participants who were enrolled in the study and receive any amount of study treatment.

PFS as per INV was defined as time from the date of treatment initiation to date of documented PD as assessed by INV per RECIST version 1.1 or death from any cause, whichever occurred first. Participants without documentation of progression or death at the time of analysis were censored at the date of the last disease assessment. PD: at least 20 % increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered progression.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=8 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Progression Free Survival (PFS) Per INV: Phase 1b (Cohort 1E and 1F)	18.3 Months Interval 2.8 to 19.7	5.7 Months Interval 1.4 to 17.8

SECONDARY outcome

Timeframe: From date of start of study treatment until date of death or censoring date

Population: The full analysis set included all participants who were enrolled in the study and receive any amount of study treatment.

OS was defined as the time from treatment initiation to death due to any cause. For a participant who was not known to have died by the end of study follow-up, observation of OS was censored on date the participant was last known to be alive (i.e., the date of last contact). Participants lacking data beyond the day of treatment initiation had their survival time censored on date of treatment initiation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Predose on Day 1 of Cycle 2

Population: The PK analysis set included all participants in the safety set from whom at least one PK assessment was reported. Here "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.

PK parameters were determined using noncompartmental analysis.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B n=5 Participants Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Ctrough of Tucatinib: Phase 1b (Cohort 1E and 1F)	199 ng/mL Geometric Coefficient of Variation 147	185 ng/mL Geometric Coefficient of Variation 113

SECONDARY outcome

Timeframe: From the first dose of study treatment until the first documented CR or PR or before start of any new anti-cancer therapy (up to 20.9 months)

cORR was defined as the percentage of participants with a confirmed CR or PR per investigator according to RECIST v1.1. For a response to be considered confirmed, the subsequent response had to be at least 4 weeks after the initial response. CR: complete disappearance of all target lesions with exception of nodal disease and complete disappearance of non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: a \>= 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. 90% exact CI was based on Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Confirmed Objective Response Rate (cORR) Per INV: Phase 2 (Cohort 2B)	80.0 Percentage of participants Interval 34.3 to 99.0	—

SECONDARY outcome

Timeframe: From the first documented objective response until the first documentation of PD or death, whichever occurred first (up to 19.9 months)

Population: The response evaluable set included all participants who met all following criteria- had measurable disease at baseline, received any amount of study treatment, and had at least one post-baseline disease assessment or discontinued due to clinical progression, toxicity or death. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for the outcome measure.

Outcome measures

Outcome measures
Measure	Cohort 1A n=4 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
DOR Per INV: Phase 2 (Cohort 2B)	NA Months Interval 11.2 to Median and upper limit of 90% CI could not be estimated due to insufficient number of participants with events	—

SECONDARY outcome

Timeframe: From the first dose of study treatment until the first documented PD or death from any cause or censoring date, whichever occurred first (up to 20.9 months)

Population: The FAS included all participants who were enrolled in the study and receive any amount of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1A n=5 Participants Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	Cohort 1B Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
PFS Per INV: Phase 2 (Cohort 2B)	13.8 Months Interval 4.6 to 20.9	—

SECONDARY outcome

Timeframe: From date of start of study treatment until date of death or censoring date

Population: The FAS included all participants who were enrolled in the study and receive any amount of study treatment.

Outcome measures

Outcome data not reported

Adverse Events

COHORT 1A

Serious events: 1 serious events

Other events: 5 other events

Deaths: 1 deaths

COHORT 1B

Serious events: 5 serious events

Other events: 11 other events

Deaths: 4 deaths

COHORT 1D

Serious events: 3 serious events

Other events: 7 other events

Deaths: 4 deaths

COHORT 1E

Serious events: 1 serious events

Other events: 4 other events

Deaths: 1 deaths

COHORT 1F

Serious events: 6 serious events

Other events: 8 other events

Deaths: 6 deaths

COHORT 2B

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	COHORT 1A n=5 participants at risk Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	COHORT 1B n=11 participants at risk Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	COHORT 1D n=7 participants at risk Japanese participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	COHORT 1E n=4 participants at risk Participants received tucatinib 300 mg PO BID on Days 1 to 14 (Each cycle = 14 Days), trastuzumab Q3W 8 mg/kg via IV infusion on Day 1 of Cycle 1 and then 6 mg/kg Q3W starting on Day 1 of Cycle 2 (Each cycle = 21 Days), mFOLFOX 6 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle (Each cycle = 14 Days) and pembrolizumab 400 mg IV on Day 1 of Cycle 1 and then Q6W starting on Day 1 of Cycle2 (Each cycle = 42 days). Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	COHORT 1F n=8 participants at risk Participants received tucatinib 300 mg PO BID on Days 1 to 14, trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 6 mg/kg Q3W starting on Day 1 of Cycle 2 (Each cycle = 21 days), CAPOX (oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000mg/m\^2 PO BID on evening of Day 1 to morning of Day 15 of Cycle 1 and Day 1 to 14 of each subsequent cycle) (Each cycle = 21 Days) and pembrolizumab 400 mg IV on Day 1 of Cycle 1 and then Q6W starting on Day 1 of Cycle 2. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	COHORT 2B n=5 participants at risk Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 8 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 6 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Cardiac disorders Myocardial infarction	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Eye disorders Visual impairment	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Abdominal pain	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Constipation	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Diarrhoea	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Duodenal stenosis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
General disorders Pyrexia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Hepatobiliary disorders Bile duct stenosis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Hepatobiliary disorders Drug-induced liver injury	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Hepatobiliary disorders Immune-mediated hepatitis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Immune system disorders Drug hypersensitivity	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Bacteraemia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Diverticulitis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Necrotising soft tissue infection	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Pelvic abscess	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Metabolism and nutrition disorders Dehydration	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Cerebral infarction	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Syncope	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Aspiration	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Pneumonitis aspiration	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.

Other adverse events

Other adverse events
Measure	COHORT 1A n=5 participants at risk Participants received tucatinib 150 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	COHORT 1B n=11 participants at risk Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	COHORT 1D n=7 participants at risk Japanese participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 6 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 4 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	COHORT 1E n=4 participants at risk Participants received tucatinib 300 mg PO BID on Days 1 to 14 (Each cycle = 14 Days), trastuzumab Q3W 8 mg/kg via IV infusion on Day 1 of Cycle 1 and then 6 mg/kg Q3W starting on Day 1 of Cycle 2 (Each cycle = 21 Days), mFOLFOX 6 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle (Each cycle = 14 Days) and pembrolizumab 400 mg IV on Day 1 of Cycle 1 and then Q6W starting on Day 1 of Cycle2 (Each cycle = 42 days). Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	COHORT 1F n=8 participants at risk Participants received tucatinib 300 mg PO BID on Days 1 to 14, trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 6 mg/kg Q3W starting on Day 1 of Cycle 2 (Each cycle = 21 days), CAPOX (oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000mg/m\^2 PO BID on evening of Day 1 to morning of Day 15 of Cycle 1 and Day 1 to 14 of each subsequent cycle) (Each cycle = 21 Days) and pembrolizumab 400 mg IV on Day 1 of Cycle 1 and then Q6W starting on Day 1 of Cycle 2. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.	COHORT 2B n=5 participants at risk Participants received tucatinib 300 mg PO BID on Days 1 to 14, loading dose of trastuzumab at 8 mg/kg via IV infusion on Day 1 of Cycle 1 followed by 6 mg/kg Q2W starting on Cycle 2 Day 1 and mFOLFOX6 or mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin 400 mg/m\^2 \[mFOLFOX6\] or 200 mg/m\^2 \[mFOLFOX7\] administered IV, fluorouracil 400 mg/m\^2 \[IV bolus\] \[mFOLFOX6\] and then fluorouracil 2400 mg/m\^2 administered IV over 46 hours) on Day 1 of each cycle. Each cycle was of 14 days. Participants continued on therapy until PD, unacceptable toxicity, withdrawal of consent, death, or study closure.
Blood and lymphatic system disorders Anaemia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	28.6% 2/7 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Blood and lymphatic system disorders Increased tendency to bruise	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Blood and lymphatic system disorders Leukopenia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	71.4% 5/7 • Number of events 22 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	50.0% 2/4 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Blood and lymphatic system disorders Lymphopenia	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Blood and lymphatic system disorders Neutropenia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	27.3% 3/11 • Number of events 5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	85.7% 6/7 • Number of events 24 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	100.0% 4/4 • Number of events 10 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 6 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	80.0% 4/5 • Number of events 5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	36.4% 4/11 • Number of events 8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	42.9% 3/7 • Number of events 21 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	50.0% 2/4 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	80.0% 4/5 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Cardiac disorders Atrial fibrillation	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Cardiac disorders Bradycardia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Cardiac disorders Coronary artery disease	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Cardiac disorders Left ventricular hypertrophy	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Cardiac disorders Right ventricular dysfunction	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Cardiac disorders Ventricular hypokinesia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Ear and labyrinth disorders Ear pruritus	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Ear and labyrinth disorders Vertigo	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Endocrine disorders Hypothyroidism	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Eye disorders Cataract	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Eye disorders Eye swelling	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Eye disorders Lacrimation increased	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Eye disorders Photophobia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Eye disorders Retinal haemorrhage	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Eye disorders Vision blurred	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Abdominal distension	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Abdominal hernia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Abdominal pain	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Constipation	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	57.1% 4/7 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Diarrhoea	60.0% 3/5 • Number of events 6 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	100.0% 11/11 • Number of events 91 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	71.4% 5/7 • Number of events 6 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	75.0% 3/4 • Number of events 5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	100.0% 8/8 • Number of events 18 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	100.0% 5/5 • Number of events 11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Dry mouth	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Dyspepsia	40.0% 2/5 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	27.3% 3/11 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Dysphagia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Eructation	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Flatulence	40.0% 2/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Gastrointestinal erosion	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Gastrointestinal pain	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Haemorrhoids	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Hypoaesthesia oral	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Nausea	60.0% 3/5 • Number of events 8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	45.5% 5/11 • Number of events 6 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	42.9% 3/7 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	75.0% 3/4 • Number of events 10 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	75.0% 6/8 • Number of events 13 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	40.0% 2/5 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Oral dysaesthesia	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Pigmentation lip	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Stomatitis	40.0% 2/5 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	36.4% 4/11 • Number of events 18 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	28.6% 2/7 • Number of events 6 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	50.0% 2/4 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	50.0% 4/8 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Gastrointestinal disorders Vomiting	40.0% 2/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	45.5% 5/11 • Number of events 11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	50.0% 2/4 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	50.0% 4/8 • Number of events 7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
General disorders Chest discomfort	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
General disorders Chills	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
General disorders Fatigue	60.0% 3/5 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	81.8% 9/11 • Number of events 14 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	42.9% 3/7 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	50.0% 2/4 • Number of events 8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
General disorders Feeling jittery	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
General disorders Hernia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
General disorders Malaise	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	37.5% 3/8 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	40.0% 2/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
General disorders Non-cardiac chest pain	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
General disorders Oedema peripheral	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	45.5% 5/11 • Number of events 5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
General disorders Pain	20.0% 1/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
General disorders Peripheral swelling	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
General disorders Pyrexia	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	62.5% 5/8 • Number of events 10 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
General disorders Temperature intolerance	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
General disorders Thirst	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	37.5% 3/8 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	40.0% 2/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Immune system disorders Contrast media allergy	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Biliary tract infection	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	28.6% 2/7 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations COVID-19	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	27.3% 3/11 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Conjunctivitis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Cystitis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Ear infection	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Eye infection	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Fungal infection	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Gingivitis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Influenza	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Nasopharyngitis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	37.5% 3/8 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Omphalitis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Oral herpes	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Periorbital cellulitis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Pharyngitis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Pneumonia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Respiratory tract infection viral	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Rhinitis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Sepsis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Sinusitis	20.0% 1/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Skin infection	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Tooth infection	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Upper respiratory tract infection	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Infections and infestations Urinary tract infection	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Injury, poisoning and procedural complications Contusion	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Injury, poisoning and procedural complications Fall	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	28.6% 2/7 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Injury, poisoning and procedural complications Overdose	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Investigations Alanine aminotransferase increased	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	28.6% 2/7 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	40.0% 2/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Investigations Aspartate aminotransferase increased	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	28.6% 2/7 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Investigations Blood alkaline phosphatase increased	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Investigations Blood bilirubin increased	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Investigations Blood creatine increased	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Investigations Blood creatinine increased	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Investigations C-reactive protein increased	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Investigations Cystatin C increased	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Investigations Ejection fraction decreased	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Investigations Glomerular filtration rate decreased	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Investigations Weight decreased	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	36.4% 4/11 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	50.0% 2/4 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Metabolism and nutrition disorders Decreased appetite	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	63.6% 7/11 • Number of events 8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	42.9% 3/7 • Number of events 5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	100.0% 4/4 • Number of events 11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	62.5% 5/8 • Number of events 6 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	60.0% 3/5 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Metabolism and nutrition disorders Dehydration	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Metabolism and nutrition disorders Fluid retention	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	50.0% 2/4 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Musculoskeletal and connective tissue disorders Back pain	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	28.6% 2/7 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Musculoskeletal and connective tissue disorders Joint hyperextension	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Musculoskeletal and connective tissue disorders Joint lock	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	27.3% 3/11 • Number of events 11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Musculoskeletal and connective tissue disorders Periarthritis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Brain fog	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Cold dysaesthesia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Dizziness	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	36.4% 4/11 • Number of events 10 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Dysgeusia	40.0% 2/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	27.3% 3/11 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Headache	20.0% 1/5 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	45.5% 5/11 • Number of events 7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	37.5% 3/8 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Hypoaesthesia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Neuralgia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Neuropathy peripheral	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	27.3% 3/11 • Number of events 7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Paraesthesia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Peripheral sensorimotor neuropathy	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Peripheral sensory neuropathy	40.0% 2/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	45.5% 5/11 • Number of events 7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	42.9% 3/7 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	62.5% 5/8 • Number of events 6 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	80.0% 4/5 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Somnolence	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Nervous system disorders Vocal cord paralysis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Psychiatric disorders Anxiety	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Psychiatric disorders Depression	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Psychiatric disorders Hallucination	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Psychiatric disorders Insomnia	20.0% 1/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Psychiatric disorders Mental disorder	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Renal and urinary disorders Dysuria	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Renal and urinary disorders Glycosuria	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Renal and urinary disorders Haematuria	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Renal and urinary disorders Nephrolithiasis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Renal and urinary disorders Pollakiuria	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Renal and urinary disorders Proteinuria	40.0% 2/5 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Renal and urinary disorders Ureteric stenosis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Reproductive system and breast disorders Genital haemorrhage	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Bronchospasm	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Cough	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Dysphonia	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	27.3% 3/11 • Number of events 7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Laryngeal pain	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal discomfort	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Pulmonary toxicity	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	27.3% 3/11 • Number of events 5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Acne	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	50.0% 2/4 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Cold sweat	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Dermal cyst	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	45.5% 5/11 • Number of events 9 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	75.0% 3/4 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	50.0% 2/4 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Nail bed inflammation	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Onychoclasis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	50.0% 2/4 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	50.0% 4/8 • Number of events 7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Photosensitivity reaction	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	27.3% 3/11 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 2/8 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	40.0% 2/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Rash	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	50.0% 2/4 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Skin exfoliation	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 3 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Skin induration	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Vascular disorders Flushing	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	9.1% 1/11 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	14.3% 1/7 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Vascular disorders Hot flush	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	18.2% 2/11 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Vascular disorders Hypertension	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	27.3% 3/11 • Number of events 4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 2 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Vascular disorders Hypotension	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	25.0% 1/4 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/8 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	20.0% 1/5 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.
Vascular disorders Vasculitis	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/11 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/7 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/4 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	12.5% 1/8 • Number of events 1 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.	0.00% 0/5 • All-cause mortality: maximum up to 38.2 months for cohort 1A, 1B and 1D; 24.1 months for cohort 1E and 1F and 20.9 months for cohort 2B. For Treatment emergent SAEs and non-SAEs- From first dose of study treatment (Day 1) up to 30 days after last dose, end of study date, death date/ data cutoff date, whichever was earlier (maximum of 38.2 months: cohort 1A and 1B; 21 months: cohort 1D; 20.7 months: cohort 1E and1F; 20.9 months: cohort 2B) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All enrolled analysis set included all participants who were enrolled in the study.

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publication until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
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