Trial Outcomes & Findings for Study of PI3Kinase Inhibition (Copanlisib) and Anti-PD-1 Antibody Nivolumab in Relapsed/Refractory Solid Tumors With Expansions in Mismatch-repair Proficient (MSS) Colorectal Cancer (NCT NCT03711058)

Last Updated: 2025-09-16

Results Overview

Number of participants experiencing a Dose Limiting Toxicity (DLT) in each dose level. DLT is defined as any of the following study drug-related toxicities occurring during the first cycle of study drug on study: * Grade 4 anemia * Grade ≥ 3 neutropenia lasting ≥ 14 days * Grade ≥ 3 febrile neutropenia * Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with clinically significant bleeding * Treatment-related ≥ grade 4 AEs, except transient hyperglycemia * Grade ≥ 3 Pneumonitis or recurrent Grade 2 pneumonitis * Grade ≥ 3 Nephritis * Grade ≥ 3 elevated AST or ALT * Grade ≥ 2 eye pain or reduction of visual acuity that does not respond to topical therapy, improve to ≤ grade 1 within 2 weeks of topical therapy, or requires systemic therapy * Any other Grade ≥ 3 toxicities (with certain exceptions for transient AEs or asymptomatic labs)

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

48 participants

Primary outcome timeframe

28 days

Results posted on

2025-09-16

Participant Flow

9 participants (1 from Phase 1, 4 from Phase 2 Cohort A and 4 from Phase 2 Cohort B) were excluded from analysis because they did not receive the study drug.

Participant milestones

Participant milestones
Measure	Phase I - Dose Finding Copanlisib will be administered as a 60-minute IV infusion (-5min/+10min) at one of three dose levels: Dose Level 1: 60mg on Day 1, 8, and 15 Dose Level -1: 60mg on Day 1 and 15 Dose Level -2: 45 mg on Day 1 and 15 Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each cycle. Cycle length is 28 days. Only Dose Level 1 was tested.	Phase II /Cohort A - PI3K Mutation Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort B - PI3K Wild Type Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.
Overall Study STARTED	6	21	12
Overall Study COMPLETED	6	21	12
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of PI3Kinase Inhibition (Copanlisib) and Anti-PD-1 Antibody Nivolumab in Relapsed/Refractory Solid Tumors With Expansions in Mismatch-repair Proficient (MSS) Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I - Dose Finding n=6 Participants Copanlisib: Copanlisib will be administered as a 60 minute IV infusion (-5min/+10min) at one of three dose levels: Dose Level 1: 60mg on Day 1, 8, and 15 Dose Level -1: 60mg on Day 1 and 15 Dose Level -2: 45 mg on Day 1 and 15 Nivolumab: Nivolumab 480 mg will be administered as a 30 minute IV infusion (-5min/+10min) on Day 1 of each cycle. Cycle length is 28 days. Only Dose Level 1 was tested.	Phase II /Cohort A - PI3K Mutation n=21 Participants Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II/Cohort B - PI3K Wild Type n=12 Participants Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Total n=39 Participants Total of all reporting groups
Age, Continuous	59.5 years n=5 Participants	57 years n=7 Participants	58.5 years n=5 Participants	58 years n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	15 Participants n=7 Participants	4 Participants n=5 Participants	21 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	18 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	20 Participants n=7 Participants	11 Participants n=5 Participants	37 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	15 Participants n=7 Participants	10 Participants n=5 Participants	30 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	6 Participants n=5 Participants	21 Participants n=7 Participants	12 Participants n=5 Participants	39 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Classification of Participants ECOG 0	3 Participants n=5 Participants	11 Participants n=7 Participants	4 Participants n=5 Participants	18 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Classification of Participants ECOG 1	3 Participants n=5 Participants	10 Participants n=7 Participants	8 Participants n=5 Participants	21 Participants n=4 Participants

PRIMARY outcome

Timeframe: 28 days

Population: Per protocol, Dose Limiting Toxicities (DLTs) were only assessed in Phase I subjects in order to determine the Phase II dose of copanlisib. Since no subjects experienced DLTs in Dose Level 1, this was the only dose level tested.

Outcome measures

Outcome measures
Measure	Phase I - Dose Finding (Dose Level 1) n=6 Participants Copanlisib will be administered as a 60-minute IV infusion (-5min/+10min) at Dose Level 1: 60mg on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort A- PI3K Mutation Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort B- PI3K Wild Type Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.
Number of Participants Experiencing a Dose Limiting Toxicity	0 Participants	—	—

PRIMARY outcome

Timeframe: 6-months

The proportion of subjects with partial response (PR) or complete response (CR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per RECIST 1.1, complete response is defined as disappearance of all target lesions, and partial response is defined as at least a 30% decrease in the sum of diameters of target lesions. Lesions are assessed by CT or MRI.

Outcome measures

Outcome measures
Measure	Phase I - Dose Finding (Dose Level 1) n=6 Participants Copanlisib will be administered as a 60-minute IV infusion (-5min/+10min) at Dose Level 1: 60mg on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort A- PI3K Mutation n=21 Participants Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort B- PI3K Wild Type n=12 Participants Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.
6-month Objective Response Rate (ORR) of Patients Treated With Copanlisib and Nivolumab	0 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: 6-months

Percentage of participants achieving stable disease (SD) or better (SD + PR + CR). Per RECIST 1.1, complete response is defined as disappearance of all target lesions, partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, stable disease occurs when there is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least 20% increase). Lesions are assessed by CT or MRI.

Outcome measures

Outcome measures
Measure	Phase I - Dose Finding (Dose Level 1) n=6 Participants Copanlisib will be administered as a 60-minute IV infusion (-5min/+10min) at Dose Level 1: 60mg on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort A- PI3K Mutation n=21 Participants Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort B- PI3K Wild Type n=12 Participants Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.
Disease Control Rate (DCR) Status at 6 Months.	0 Participants	5 Participants	3 Participants

SECONDARY outcome

Timeframe: 3 years

Population: Only patients who had a partial or complete response by RECIST were evaluable for duration of response.

Number of months from the first documentation of a partial or complete response by RECIST 1.1 to date of disease progression. Responses may be documented at any time on the study, including patients responding after the 6-month evaluation used for the primary outcome.

Outcome measures

Outcome measures
Measure	Phase I - Dose Finding (Dose Level 1) Copanlisib will be administered as a 60-minute IV infusion (-5min/+10min) at Dose Level 1: 60mg on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort A- PI3K Mutation n=3 Participants Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort B- PI3K Wild Type n=1 Participants Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.
Duration of Response (DOR)	—	20.6 months Interval 17.0 to 22.8	13.1 months Interval 13.1 to 13.1

SECONDARY outcome

Timeframe: 3 years

Number of months from treatment to disease progression (PD)

Outcome measures

Outcome measures
Measure	Phase I - Dose Finding (Dose Level 1) n=6 Participants Copanlisib will be administered as a 60-minute IV infusion (-5min/+10min) at Dose Level 1: 60mg on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort A- PI3K Mutation n=21 Participants Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort B- PI3K Wild Type n=12 Participants Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.
Progression Free Survival (PFS)	1.64 months Interval 1.38 to Upper bound confidence interval was not estimable due to insufficient number of events	1.68 months Interval 1.64 to Upper bound confidence interval was not estimable due to insufficient number of events	1.82 months Interval 1.68 to Upper bound confidence interval was not estimable due to insufficient number of events

SECONDARY outcome

Timeframe: 3 years

Number of months from the date of first treatment until death or end of follow-up.

Outcome measures

Outcome measures
Measure	Phase I - Dose Finding (Dose Level 1) n=6 Participants Copanlisib will be administered as a 60-minute IV infusion (-5min/+10min) at Dose Level 1: 60mg on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort A- PI3K Mutation n=21 Participants Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort B- PI3K Wild Type n=12 Participants Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.
Overall Survival (OS)	5.61 months Interval 2.4 to Upper bound confidence interval was not estimable due to insufficient number of events	6.77 months Interval 4.21 to 16.04	10.26 months Interval 4.8 to Upper bound confidence interval was not estimable due to insufficient number of events

SECONDARY outcome

Timeframe: 51 months

Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0.

Outcome measures

Outcome measures
Measure	Phase I - Dose Finding (Dose Level 1) n=6 Participants Copanlisib will be administered as a 60-minute IV infusion (-5min/+10min) at Dose Level 1: 60mg on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort A- PI3K Mutation n=21 Participants Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort B- PI3K Wild Type n=12 Participants Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.
Number of Participants Experiencing Study Drug-related Toxicities	5 Participants	16 Participants	10 Participants

Adverse Events

Phase I - Dose Finding (Dose Level 1)

Serious events: 3 serious events

Other events: 6 other events

Deaths: 6 deaths

Phase II /Cohort A - PI3K Mutation

Serious events: 11 serious events

Other events: 21 other events

Deaths: 14 deaths

Phase II /Cohort B - PI3K Wild Type

Serious events: 6 serious events

Other events: 12 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Nilofer Azad, MD

Sidney Kimmel Cancer Center at Johns Hopkins

Phone: 610-614-9169

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase I - Dose Finding (Dose Level 1) n=6 participants at risk Copanlisib will be administered as a 60-minute IV infusion (-5min/+10min) at Dose Level 1: 60mg on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort A - PI3K Mutation n=21 participants at risk Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.	Phase II /Cohort B - PI3K Wild Type n=12 participants at risk Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle. Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	9.5% 2/21 • Number of events 2 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	8.3% 1/12 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Gastrointestinal disorders Chylous ascites	16.7% 1/6 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/21 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/12 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Gastrointestinal disorders Colitis	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	14.3% 3/21 • Number of events 3 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/12 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Gastrointestinal disorders Colonic obstruction	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	4.8% 1/21 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	8.3% 1/12 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Gastrointestinal disorders Colonic perforation	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	4.8% 1/21 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/12 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Gastrointestinal disorders Diarrhea	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	4.8% 1/21 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/12 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Gastrointestinal disorders Nausea	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	4.8% 1/21 • Number of events 2 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	8.3% 1/12 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/21 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	8.3% 1/12 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Gastrointestinal disorders Vomiting	16.7% 1/6 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	4.8% 1/21 • Number of events 2 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/12 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
General disorders Disease progression	50.0% 3/6 • Number of events 3 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	19.0% 4/21 • Number of events 4 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	25.0% 3/12 • Number of events 3 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
General disorders Fever	16.7% 1/6 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/21 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	16.7% 2/12 • Number of events 2 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Hepatobiliary disorders Hepatic failure	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/21 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	8.3% 1/12 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Injury, poisoning and procedural complications Hip fracture	16.7% 1/6 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/21 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/12 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	4.8% 1/21 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	8.3% 1/12 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Metabolism and nutrition disorders Hypokalemia	16.7% 1/6 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/21 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/12 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/21 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	8.3% 1/12 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/21 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	8.3% 1/12 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Respiratory, thoracic and mediastinal disorders Chylothorax	16.7% 1/6 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/21 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/12 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/21 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	8.3% 1/12 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Skin and subcutaneous tissue disorders Rash maculopapular	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	4.8% 1/21 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	8.3% 1/12 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Vascular disorders Thromboembolic event	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	4.8% 1/21 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/12 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Gastrointestinal disorders Oral Mucositis	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/21 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	8.3% 1/12 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Respiratory, thoracic and mediastinal disorders Vocal Cord Paralysis	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/21 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	8.3% 1/12 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Infections and infestations Sepsis	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	4.8% 1/21 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	8.3% 1/12 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	4.8% 1/21 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/12 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements
Endocrine disorders Thyroiditis	0.00% 0/6 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	4.8% 1/21 • Number of events 1 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements	0.00% 0/12 • Up to 51 months Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements