Trial Outcomes & Findings for This Study Aims to Find a Safe and Effective Dose of BI 754091. The Study Also Aims to Find Safe and Effective Doses of BI 754091 and BI 754111 in Combination. This Study is Done in Asian Patients With Different Types of Cancer (NCT NCT03433898)

Last Updated: 2025-12-19

Results Overview

MTD is defined as the highest dose for a given schedule expected to cause \<25% risk of the true dose limiting toxicity (DLT) rate being ≥33% during the MTD evaluation period. Haematologic DLTs: any Grade 5 toxicity; neutropenia ≥Grade 4 for \>5 days; any duration Febrile neutropenia; grade 4 thrombocytopenia or Grade 3 with bleeding or requiring platelet transfusions (any Grade); unexplained Grade 4 anaemia or requiring blood transfusions (any Grade). Non-haematological DLTs: aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \>3x Upper limit of normal (ULN) and total bilirubin \>2x ULN without cholestasis signs; any duration ≥Grade 4 AST or ALT; any ≥Grade 3 non-haematologic toxicity with exceptions; any Grade 4 or 5 adverse event; any duration any Grade 2 pneumonitis; any Grade 2 uveitis, eye pain, or blurred vision not improving to Grade 1 within 2 weeks or requiring systemic treatment; any ≥Grade 2 toxicity causing inability to administer trial drug on Cycle 2 Day 1.

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

146 participants

Primary outcome timeframe

First cycle of treatment: 3 weeks (21 days) following drug administration.

Results posted on

2025-12-19

Participant Flow

This is a Phase I, open-label, non-randomised trial in patients with advanced solid tumours to investigate safety, tolerability, pharmacokinetics (PK), maximum tolerated dose (MTD) and/or recommended dose (RD) of BI 754091 (ezabenlimab) as monotherapy (part I), safety, tolerability, PK and RD of ezabenlimab and BI 754111 as combination therapy (part II), and to further investigate the safety, tolerability, PK and efficacy of the combination of ezabenlimab and BI 754111 at RD (part III).

All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Participant milestones

Participant milestones
Measure	Part I - ezabenlimab 240 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 400 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 400 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 600 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 800 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 800 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort A Patients with gastric/esophagogastric junction cancer, with no prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, and who had received at least one line of systemic anticancer treatment, excluding adjuvant therapy, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort B Patients with esophageal cancer, with no prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, and who had received at least one line of systemic anticancer treatment, excluding adjuvant therapy, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort C Patients with hepatocellular cancer, with no prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, who received at least one line of systemic anticancer treatment, excluding adjuvant therapy, and whose Child-Pugh score is ≤7, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort D Patients with gastric/esophagogastric junction cancer, esophageal cancer, or hepatocellular cancer, with a prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.
Overall Study NOT COMPLETED	7	3	3	2	34	34	20	33
Overall Study STARTED	7	3	3	3	37	37	20	36
Overall Study Treated	6	3	3	3	36	37	20	36
Overall Study COMPLETED	0	0	0	1	3	3	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Part I - ezabenlimab 240 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 400 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 400 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 600 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 800 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 800 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort A Patients with gastric/esophagogastric junction cancer, with no prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, and who had received at least one line of systemic anticancer treatment, excluding adjuvant therapy, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort B Patients with esophageal cancer, with no prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, and who had received at least one line of systemic anticancer treatment, excluding adjuvant therapy, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort C Patients with hepatocellular cancer, with no prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, who received at least one line of systemic anticancer treatment, excluding adjuvant therapy, and whose Child-Pugh score is ≤7, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort D Patients with gastric/esophagogastric junction cancer, esophageal cancer, or hepatocellular cancer, with a prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.
Overall Study Progressive disease	6	3	3	2	30	29	17	30
Overall Study Not treated	1	0	0	0	1	0	0	0
Overall Study Death	0	0	0	0	0	0	1	1
Overall Study Withdrawal by Subject	0	0	0	0	2	0	0	0
Overall Study Adverse Event	0	0	0	0	0	5	2	2
Overall Study Fatal adverse event: Acute kidney injury	0	0	0	0	1	0	0	0

Baseline Characteristics

This Study Aims to Find a Safe and Effective Dose of BI 754091. The Study Also Aims to Find Safe and Effective Doses of BI 754091 and BI 754111 in Combination. This Study is Done in Asian Patients With Different Types of Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part I - Ezabenlimab 240 mg n=6 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - Ezabenlimab 240 mg + BI 754111 400 mg n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 400 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - Ezabenlimab 240 mg + BI 754111 600 mg n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - Ezabenlimab 240 mg + BI 754111 800 mg n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 800 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - Ezabenlimab 240 mg + BI 754111 600 mg, Cohort A n=36 Participants Patients with gastric/esophagogastric junction cancer, with no prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, and who had received at least one line of systemic anticancer treatment, excluding adjuvant therapy, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - Ezabenlimab 240 mg + BI 754111 600 mg, Cohort B n=37 Participants Patients with esophageal cancer, with no prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, and who had received at least one line of systemic anticancer treatment, excluding adjuvant therapy, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - Ezabenlimab 240 mg + BI 754111 600 mg, Cohort C n=20 Participants Patients with hepatocellular cancer, with no prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, who received at least one line of systemic anticancer treatment, excluding adjuvant therapy, and whose Child-Pugh score is ≤7, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - Ezabenlimab 240 mg + BI 754111 600 mg, Cohort D n=36 Participants Patients with gastric/esophagogastric junction cancer, esophageal cancer, or hepatocellular cancer, with a prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Total n=144 Participants Total of all reporting groups
Age, Continuous	55.3 Years STANDARD_DEVIATION 15.2 • n=8 Participants	65.0 Years STANDARD_DEVIATION 6.2 • n=6 Participants	59.0 Years STANDARD_DEVIATION 16.1 • n=6 Participants	45.7 Years STANDARD_DEVIATION 26.3 • n=9 Participants	57.2 Years STANDARD_DEVIATION 14.0 • n=6 Participants	62.5 Years STANDARD_DEVIATION 8.6 • n=195 Participants	58.9 Years STANDARD_DEVIATION 12.9 • n=585 Participants	60.5 Years STANDARD_DEVIATION 10.4 • n=19829 Participants	59.5 Years STANDARD_DEVIATION 12.1 • n=77547 Participants
Sex: Female, Male Female	2 Participants n=8 Participants	1 Participants n=6 Participants	3 Participants n=6 Participants	1 Participants n=9 Participants	10 Participants n=6 Participants	6 Participants n=195 Participants	2 Participants n=585 Participants	7 Participants n=19829 Participants	32 Participants n=77547 Participants
Sex: Female, Male Male	4 Participants n=8 Participants	2 Participants n=6 Participants	0 Participants n=6 Participants	2 Participants n=9 Participants	26 Participants n=6 Participants	31 Participants n=195 Participants	18 Participants n=585 Participants	29 Participants n=19829 Participants	112 Participants n=77547 Participants
Race/Ethnicity, Customized Asian	6 Participants n=8 Participants	3 Participants n=6 Participants	3 Participants n=6 Participants	3 Participants n=9 Participants	36 Participants n=6 Participants	37 Participants n=195 Participants	20 Participants n=585 Participants	36 Participants n=19829 Participants	144 Participants n=77547 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	6 Participants n=8 Participants	3 Participants n=6 Participants	3 Participants n=6 Participants	3 Participants n=9 Participants	36 Participants n=6 Participants	37 Participants n=195 Participants	20 Participants n=585 Participants	36 Participants n=19829 Participants	144 Participants n=77547 Participants

PRIMARY outcome

Timeframe: First cycle of treatment: 3 weeks (21 days) following drug administration.

Population: Maximum tolerated dose set (MTDS) restricted to Part I: included all patients who were documented to have received at least one dose of ezabenlimab in Part I and were not replaced for the MTD determination. Patients who discontinued during the first treatment course for reasons other than a DLT were excluded from the determination of the MTD. The MTDS was used for the primary analyses of DLTs and MTD determination.

Outcome measures

Outcome measures
Measure	Part I - ezabenlimab 240 mg n=6 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 600 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 800 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 800 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort D Patients with gastric/esophagogastric junction cancer, esophageal cancer, or hepatocellular cancer, with a prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.
Part I: Maximum Tolerated Dose (MTD) of Ezabenlimab	NA Milligram There was no DLT in Part I of this trial during the first cycle and, therefore, an MTD was not reached within the investigated dose range.	—	—	—

PRIMARY outcome

Timeframe: First cycle of treatment: 3 weeks (21 days) following drug administration.

Number of patients experiencing DLTs during the MTD evaluation period (first cycle of treatment) is reported.

Outcome measures

Outcome measures
Measure	Part I - ezabenlimab 240 mg n=6 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 600 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 800 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 800 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort D Patients with gastric/esophagogastric junction cancer, esophageal cancer, or hepatocellular cancer, with a prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.
Part I: Number of Patients Experiencing DLTs During the MTD Evaluation Period (First Cycle of Treatment)	0 Participants	—	—	—

PRIMARY outcome

Timeframe: First cycle of treatment: 3 weeks (21 days) following drug administration.

Population: Maximum tolerated dose set (MTDS) restricted to Part II: included all patients who were documented to have received at least one dose of ezabenlimab or BI 754111 in Part II and were not replaced for the MTD determination. Patients who discontinued during the first treatment course for reasons other than a DLT were excluded from the determination of the MTD. The MTDS was used for the primary analyses of DLTs and MTD determination.

MTD is defined as the highest dose for a given schedule expected to cause \<25% risk of the true DLT rate being ≥33% during the MTD evaluation period. Haematologic DLTs: any Grade 5 toxicity; neutropenia ≥Grade 4 for \>5 days; any duration Febrile neutropenia; grade 4 thrombocytopenia or Grade 3 with bleeding or requiring platelet transfusions (any Grade); unexplained Grade 4 anaemia or requiring blood transfusions (any Grade). Non-haematological DLTs: aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \>3x Upper limit of normal (ULN) and total bilirubin \>2x ULN without cholestasis signs; any duration ≥Grade 4 AST or ALT; any ≥Grade 3 non-haematologic toxicity with exceptions; any Grade 4 or 5 adverse event; any duration any Grade 2 pneumonitis; any Grade 2 uveitis, eye pain, or blurred vision not improving to Grade 1 within 2 weeks or requiring systemic treatment; any ≥Grade 2 toxicity causing inability to administer trial drugs on Cycle 2 Day 1.

Outcome measures

Outcome measures
Measure	Part I - ezabenlimab 240 mg n=9 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 600 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 800 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 800 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort D Patients with gastric/esophagogastric junction cancer, esophageal cancer, or hepatocellular cancer, with a prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.
Part II: MTD of the Ezabenlimab Plus BI 754111 Combination Therapy	NA Milligram There was no DLT in Part II of this trial during the first cycle and, therefore, an MTD was not reached within the investigated dose range.	—	—	—

PRIMARY outcome

Timeframe: First cycle of treatment: 3 weeks (21 days) following drug administration.

Number of patients experiencing DLTs during the MTD evaluation period (first cycle of treatment) is reported.

Outcome measures

Outcome measures
Measure	Part I - ezabenlimab 240 mg n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 600 mg n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 800 mg n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 800 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort D Patients with gastric/esophagogastric junction cancer, esophageal cancer, or hepatocellular cancer, with a prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.
Part II: Number of Patients Experiencing DLTs During the MTD Evaluation Period (First Cycle of Treatment)	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period): up to 49 months.

Population: Treated set (TS) restricted to Part III: included all Part III patients who were documented to have received at least one dose of ezabenlimab or BI 754111. The TS was used for both efficacy and safety analyses. Patients with a post baseline measurement are reported here.

Number of patients with objective response (OR) - confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumours (RECIST) Version 1.1 as assessed by the Investigator, is reported. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Part I - ezabenlimab 240 mg n=33 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 600 mg n=35 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 800 mg n=20 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 800 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort D n=32 Participants Patients with gastric/esophagogastric junction cancer, esophageal cancer, or hepatocellular cancer, with a prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.
Part III: Number of Patients With Objective Response (OR) - Confirmed Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 as Assessed by the Investigator	4 Participants	8 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: From the date of objective response until first date that death or PD has been documented, up to 1362 days.

The duration of response, defined as the interval from the date of first documented PR or CR according to RECIST Version 1.1 as assessed by the Investigator, to the date of progressive disease (PD) or death, is reported. For all patients with an OR, the duration of OR was calculated as follows: * for patients with PD or death: duration of response \[days\] = date of outcome - date of first assessment indicating OR + 1, * for patients without PD or death: duration of response (censored) \[days\] = date of outcome - date of first assessment indicating OR + 1, for patients without disease progression or death. Kaplan-Meier estimates were used to calculate median duration of OR.

Outcome measures

Outcome measures
Measure	Part I - ezabenlimab 240 mg n=5 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 600 mg n=10 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 800 mg n=1 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 800 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort D n=2 Participants Patients with gastric/esophagogastric junction cancer, esophageal cancer, or hepatocellular cancer, with a prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.
Part III: Duration of Response	478.0 Days Interval 99.0 to 484.0	148.0 Days Interval 100.0 to Not enough events to calculate the 75th percentile.	44.0 Days Interval 44.0 to 44.0	209.0 Days Interval 126.0 to 292.0

SECONDARY outcome

Timeframe: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period): up to 49 months.

Number of patients with disease control is reported. Disease control: CR, PR, or stable disease (SD) according to RECIST Version 1.1 as assessed by the Investigator. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Outcome measures

Outcome measures
Measure	Part I - ezabenlimab 240 mg n=33 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 600 mg n=35 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 800 mg n=20 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 800 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort D n=32 Participants Patients with gastric/esophagogastric junction cancer, esophageal cancer, or hepatocellular cancer, with a prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.
Part III: Number of Patients With Disease Control	15 Participants	16 Participants	9 Participants	7 Participants

SECONDARY outcome

Timeframe: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period): 180 days.

Population: Treated set (TS) restricted to Part I: included all Part I patients who were documented to have received at least one dose of ezabenlimab or BI 754111. The TS was used for both efficacy and safety analyses. Patients who had a post baseline measurement are reported here.

Number of patients with OR: confirmed CR or PR according to RECIST v1.1 as assessed by the Investigator, is reported. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Part I - ezabenlimab 240 mg n=6 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 600 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part II - ezabenlimab 240 mg + BI 754111 800 mg Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 800 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.	Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort D Patients with gastric/esophagogastric junction cancer, esophageal cancer, or hepatocellular cancer, with a prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.
Part I: Number of Patients With OR: Confirmed CR or PR According to RECIST v1.1 as Assessed by the Investigator	0 Participants	—	—	—

SECONDARY outcome

Timeframe: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period): up to 389 days.

Population: Treated set (TS) restricted to Part II: included all Part II patients who were documented to have received at least one dose of ezabenlimab or BI 754111. The TS was used for both efficacy and safety analyses. Patients who had a post baseline measurement are reported here.