Trial Outcomes & Findings for A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer (NCT NCT04288089)

Last Updated: 2025-08-03

Results Overview

The MTD was defined as the highest dose at which no more than 1 of 6 participants experienced a Dose-Limiting Toxicity (DLT) in the dose cohort. DLT was graded as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. DLTs were defined as the following events that occurred in Cycle 1, for which a causal relationship with the study drug could not be ruled out: febrile neutropenia; Grade 4 neutropenia that was not resolved within 7 days; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia lasting greater than (\>) 7 days or associated with clinically significant bleeding; Grade 4 vomiting and diarrhea; Grade 3 vomiting and diarrhea lasting \> 72 hours despite treatment; Grade 4 electrolyte abnormality or Grade 3 abnormality lasting \> 24 hours; Grade 3 or 4 serum creatinine or bilirubin increase; Grade 4 biochemistry or Grade 3 lasting \> 7 days; Grade 4 or Grade 3 or intolerable grade 2 toxicities of any non-hematologic adverse event.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1

Target enrollment

31 participants

Primary outcome timeframe

Cycle 1 (Cycle length = 28 Days)

Results posted on

2025-08-03

Participant Flow

Participants took part in the study at 8 investigative sites in the United States and the United Kingdom from 1 April 2020 to 16 September 2022.

This study was planned to be conducted in two parts: Dose Escalation and Dose Expansion. In the Dose Escalation part, a total of 31 participants were enrolled and received the study treatment. However, no participants were enrolled in the Dose Expansion part. In this result summary, data has been reported for dose escalation part only and up to primary completion date (16 September 2022). This study is ongoing and will be updated with final results after study completion.

Participant milestones

Participant milestones
Measure	H3B-6545 300 mg + Palbociclib 100 mg Participants received palbociclib 100 milligram (mg) capsule, orally, once daily (QD) from Days 1 to 21 followed by H3B-6545 300 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.	H3B-6545 300 mg + Palbociclib 125 mg Participants received palbociclib 125 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 300 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.	H3B-6545 450 mg + Palbociclib 125 mg Participants received palbociclib 125 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 450 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.	H3B-6545 450 mg + Palbociclib 100 Participants received palbociclib 100 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 450 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.
Overall Study STARTED	7	8	8	8
Overall Study COMPLETED	5	7	7	4
Overall Study NOT COMPLETED	2	1	1	4

Reasons for withdrawal

Reasons for withdrawal
Measure	H3B-6545 300 mg + Palbociclib 100 mg Participants received palbociclib 100 milligram (mg) capsule, orally, once daily (QD) from Days 1 to 21 followed by H3B-6545 300 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.	H3B-6545 300 mg + Palbociclib 125 mg Participants received palbociclib 125 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 300 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.	H3B-6545 450 mg + Palbociclib 125 mg Participants received palbociclib 125 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 450 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.	H3B-6545 450 mg + Palbociclib 100 Participants received palbociclib 100 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 450 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.
Overall Study Ongoing Treatment	2	1	1	4

Baseline Characteristics

A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	H3B-6545 300 mg + Palbociclib 100 mg n=7 Participants Participants received palbociclib 100 milligram (mg) capsule, orally, once daily (QD) from Days 1 to 21 followed by H3B-6545 300 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.	H3B-6545 300 mg + Palbociclib 125 mg n=8 Participants Participants received palbociclib 125 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 300 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.	H3B-6545 450 mg + Palbociclib 125 mg n=8 Participants Participants received palbociclib 125 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 450 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.	H3B-6545 450 mg + Palbociclib 100 n=8 Participants Participants received palbociclib 100 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 450 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.	Total n=31 Participants Total of all reporting groups
Age, Continuous	62.4 Years STANDARD_DEVIATION 7.76 • n=5 Participants	51.9 Years STANDARD_DEVIATION 15.61 • n=7 Participants	56.0 Years STANDARD_DEVIATION 4.96 • n=5 Participants	59.1 Years STANDARD_DEVIATION 14.53 • n=4 Participants	57.2 Years STANDARD_DEVIATION 11.80 • n=21 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	8 Participants n=4 Participants	31 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	6 Participants n=4 Participants	29 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 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	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 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	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	5 Participants n=4 Participants	27 Participants n=21 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	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants

PRIMARY outcome

Timeframe: Cycle 1 (Cycle length = 28 Days)

Population: The Dose Evaluable Set (DES) included all participants who were evaluated for DLTs in dose escalation part.

Outcome measures

Outcome measures
Measure	All Participants n=28 Participants Participants received palbociclib (100 mg, 125 mg) from Days 1 to 21 followed by H3B-6545 (300 mg, 450 mg), from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.
Maximum Tolerated Dose (MTD) of H3B-6545 and Palbociclib Palbociclib	125 milligram
Maximum Tolerated Dose (MTD) of H3B-6545 and Palbociclib H3B-6545	300 milligram

SECONDARY outcome

Timeframe: From first dose up to 28 days after the last dose of study drug (up to Month 48)

TEAE was defined as an adverse event (AE) with an onset that had occurred after receiving study drug. An AE was defined as any untoward medical occurrence in a participants or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. A serious adverse event (SAE) was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Dose Escalation Part: Cycle 1 Days 8, 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)

Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Dose Escalation Part: Cycle 1 Days 8, 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)

Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Dose Escalation Part: Cycle 1 Days 8, 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)

Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Dose Escalation Part: Cycle 1 Days 8, 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)

Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Dose Escalation Part: Cycle 1 Days 8 and 21: 0-24 hours postdose

Ratio of palbociclib Cmax Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Dose Escalation Part: Cycle 1 Days 8 and 21: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)

Ratio of palbociclib AUC24 Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Dose Escalation Part: Cycle 1 Days 8 and 21: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)

Ratio of palbociclib C24 Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Dose Escalation Part: Cycle 1 Days 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)

Ratio of palbociclib Cmax Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Dose Escalation Part: Cycle 1 Days 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)

Ratio of H3B-6545 AUC24 Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Dose Escalation Part: Cycle 1 Days 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)

Ratio of H3B-6545 C24 Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug up to Month 48

ORR is defined as the percentage of participants achieving a best overall response (BOR) of confirmed partial response (PR) or complete response (CR). The ORR will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the date of first documented CR/PR until the PD or death, whichever occurs first (up to Month 48)

DoR is defined as the time from the date of the first documented CR/PR until the first documentation of disease progression (PD) or death, whichever comes first. The DoR will be assessed according to RECIST version 1.1. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the first dose of study drug until disease progression or death, whichever occurs first (up to Month 48)

CBR is defined as the percentage of participants with BOR of PR, CR, or durable stable disease (SD) (duration of SD greater than or equal to 23 weeks). Duration of SD is defined as the time from the date of first dose to the date of the first documentation of disease progression or death, whichever occurs first. It will be calculated for participants whose BOR is SD. The CBR will be assessed according to RECIST version 1.1. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug until first documentation of PD or death, whichever occurs first (up to Month 48)

PFS is defined as the time from the first dose date to the date of the first documentation of PD or death (whichever occurs first). Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the date of first dose to the date of death from any cause (up to Month 48)

OS is defined as the time from first dose date to the date of death from any cause. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Outcome measures

Outcome data not reported

Adverse Events

H3B-6545 300 mg + Palbociclib 100 mg

Serious events: 2 serious events

Other events: 7 other events

Deaths: 3 deaths

H3B-6545 300 mg + Palbociclib 125 mg

Serious events: 2 serious events

Other events: 7 other events

Deaths: 3 deaths

H3B-6545 450 mg + Palbociclib 125 mg

Serious events: 3 serious events

Other events: 8 other events

Deaths: 4 deaths

H3B-6545 450 mg + Palbociclib 100

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: 1-888-274-2378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	H3B-6545 300 mg + Palbociclib 100 mg n=7 participants at risk Participants received palbociclib 100 milligram (mg) capsule, orally, once daily (QD) from Days 1 to 21 followed by H3B-6545 300 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.	H3B-6545 300 mg + Palbociclib 125 mg n=8 participants at risk Participants received palbociclib 125 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 300 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.	H3B-6545 450 mg + Palbociclib 125 mg n=8 participants at risk Participants received palbociclib 125 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 450 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.	H3B-6545 450 mg + Palbociclib 100 n=8 participants at risk Participants received palbociclib 100 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 450 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/7 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Cardiac disorders Atrial fibrillation	14.3% 1/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Cardiac disorders Myocarditis	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months
Gastrointestinal disorders Colitis	0.00% 0/7 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Gastrointestinal disorders Nausea	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Gastrointestinal disorders Pancreatitis	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months
Gastrointestinal disorders Vomiting	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	25.0% 2/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
General disorders Asthenia	14.3% 1/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Hepatobiliary disorders Cholecystitis	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months
Hepatobiliary disorders Cholecystitis acute	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months
Hepatobiliary disorders Cholelithiasis	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months
Hepatobiliary disorders Hypertransaminasaemia	0.00% 0/7 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Immune system disorders Hypersensitivity	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Infections and infestations Lower respiratory tract infection	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Infections and infestations Pneumonia	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months
Injury, poisoning and procedural complications Fall	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Investigations Blood glucose increased	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Investigations Liver function test increased	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Metabolism and nutrition disorders Hypercalcaemia	14.3% 1/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	0.00% 0/7 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to stomach	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months
Nervous system disorders Dizziness	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months
Vascular disorders Hypertension	0.00% 0/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	12.5% 1/8 • First dose of study drug to approximately up to 29 months
Vascular disorders Peripheral embolism	14.3% 1/7 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months	0.00% 0/8 • First dose of study drug to approximately up to 29 months