The main objectives of the BI 754091 monotherapy dose-finding part (Part I) of the trial are to investigate the following items in advanced solid tumours: * Safety, tolerability, and pharmacokinetics (PK) of BI 754091 as monotherapy. * Maximum tolerated dose (MTD) and/or recommended dose (RD) of BI 754091 monotherapy. The main objectives of the Combination dose-finding part (Part II) of the trial are to investigate the following items in advanced solid tumours: * Safety, tolerability, and PK of the combination treatment of BI 754091 and BI 754111. * MTD and/or RD of the combination treatment of BI 754091 and BI 754111. The main objectives of the expansion part (Part III) of the trial are: * To further investigate the safety, tolerability, and PK of the RD of BI 754091 and BI 754111 combination in patients with gastric/esophagogastric junction cancer, esophageal cancer, hepatocellular cancer or non-small cell lung cancer (NSCLC) * To explore the efficacy of the RD of the combination of BI 754091 and BI 754111 in patients with gastric/esophagogastric junction cancer, esophageal cancer, hepatocellular cancer or NSCLC
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
146
Solution for infusion
Solution for infusion
National Cancer Center Hospital East
Chiba, Kashiwa, Japan
Kanagawa Cancer Center
Kanagawa, Yokohama, Japan
Saitama Cancer Center
Saitama, Kitaadachi-gun, Japan
Shizuoka Cancer Center
Shizuoka, Sunto-gun, Japan
National Cancer Center Hospital
Tokyo, Chuo-ku, Japan
Japanese Foundation for Cancer Research
Tokyo, Koto-ku, Japan
Seoul National University Hospital
Seoul, South Korea
Severance Hospital
Seoul, South Korea
Asan Medical Center
Seoul, South Korea
NCKUH
Tainan, Taiwan
...and 3 more locations
Part I: Maximum Tolerated Dose (MTD) of Ezabenlimab
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.
Time frame: First cycle of treatment: 3 weeks (21 days) following drug administration.
Part I: Number of Patients Experiencing DLTs During the MTD Evaluation Period (First Cycle of Treatment)
Number of patients experiencing DLTs during the MTD evaluation period (first cycle of treatment) is reported.
Time frame: First cycle of treatment: 3 weeks (21 days) following drug administration.
Part II: MTD of the Ezabenlimab Plus BI 754111 Combination Therapy
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.
Time frame: First cycle of treatment: 3 weeks (21 days) following drug administration.
Part II: Number of Patients Experiencing DLTs During the MTD Evaluation Period (First Cycle of Treatment)
Number of patients experiencing DLTs during the MTD evaluation period (first cycle of treatment) is reported.
Time frame: First cycle of treatment: 3 weeks (21 days) following drug administration.
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
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.
Time frame: 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.
Part III: Duration of Response
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.
Time frame: From the date of objective response until first date that death or PD has been documented, up to 1362 days.
Part III: Number of Patients With Disease Control
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.
Time frame: 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.
Part I: Number of Patients With OR: Confirmed CR or PR According to RECIST v1.1 as Assessed by the Investigator
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.
Time frame: 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.
Part II: Number of Patients With OR: Confirmed CR or PR According to RECIST v1.1 as Assessed by the Investigator
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.
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Time frame: 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.
Part I: Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) in the First Cycle of Treatment
Maximum measured concentration of ezabenlimab in plasma (Cmax) in the first cycle of treatment (21 days following drug administration) is reported.
Time frame: 5 minutes before drug administration and 1, 1.5, 2, 4, 7, 24, 48, 72, 168, 336 and 504 hours (h) after the start of drug administration in the first cycle of treatment.
Part II: Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) in the First Cycle of Treatment
Maximum measured concentration of ezabenlimab in plasma (Cmax) in the first cycle of treatment (21 days following drug administration) is reported.
Time frame: 5 minutes before drug administration and 1, 1.5, 2, 4, 7, 24, 48, 72, 168, 336 and 504 hours (h) after the start of drug administration in the first cycle of treatment.
Part II: Maximum Measured Concentration of BI 754111 in Plasma (Cmax) in the First Cycle of Treatment
Maximum measured concentration of BI 754111 in plasma (Cmax) in the first cycle of treatment (21 days following drug administration) is reported.
Time frame: 5 minutes before drug administration and 1, 1.5, 2, 4, 7, 24, 48, 72, 168, 336 and 504 hours (h) after the start of drug administration in the first cycle of treatment.
Part I: Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504) in the First Cycle of Treatment
Area under the concentration-time curve of ezabenlimab in plasma over the time interval from 0 to 504 hours (AUC0-504) in the first cycle of treatment (21 days following drug administration) is reported.
Time frame: 5 minutes before drug administration and 1, 1.5, 2, 4, 7, 24, 48, 72, 168, 336 and 504 hours (h) after the start of drug administration in the first cycle of treatment.
Part II: Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504) in the First Cycle of Treatment
Area under the concentration-time curve of ezabenlimab in plasma over the time interval from 0 to 504 hours (AUC0-504) in the first cycle of treatment (21 days following drug administration) is reported.
Time frame: 5 minutes before drug administration and 1, 1.5, 2, 4, 7, 24, 48, 72, 168, 336 and 504 hours (h) after the start of drug administration in the first cycle of treatment.
Part II: Area Under the Concentration-time Curve of BI 754111 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504) in the First Cycle of Treatment
Area under the concentration-time curve of BI 754111 in plasma over the time interval from 0 to 504 hours (AUC0-504) in the first cycle of treatment (21 days following drug administration) is reported.
Time frame: 5 minutes before drug administration and 1, 1.5, 2, 4, 7, 24, 48, 72, 168, 336 and 504 hours (h) after the start of drug administration in the first cycle of treatment.