Non-squamous, Non-Small-Cell Lung Cancer, Neoplasms
Conditions
Brief summary
This study has 2 parts. The first part was open to adults with advanced non-small cell lung cancer. The second part was open also to adults with other types of advanced cancer of the lung, brain, skin, and liver. After early encouraging results, more people with liver cancer can now take part in the study. The participants get a combination of two medicines called BI 836880 and ezabenlimab. BI 836880 is a type of an antibody that blocks new blood vessel formation. New blood vessels are needed by the tumour to continue growing. Ezabenlimab is an antibody that may help the immune system fight cancer (immune checkpoint inhibitor). The purpose of the first part of the study was to find out the highest dose of the BI 836880 that the participants can tolerate in combination with BI 754091. After the best dose of BI 836880 for the combination with ezabenlimab was found, it is used in the second part of the study. The purpose of the second part is to see whether the combination of BI 836880 and BI 754091 is able to make tumours shrink. The participants are in the study as long as they benefit from and can tolerate treatment. During this time, they get infusions of BI 836880 and ezabenlimab every 3 weeks. The doctors also regularly check the general health of the participants.
Interventions
DRUGBI 836880
BI 836880 as an intravenous infusion on day 1 of each 3-week cycle.
DRUGEzabenlimab
240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle.
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part 1: * Of full age (according to local legislation, usually ≥ 18 years) at screening. * Pathologically confirmed locally advanced or metastatic non-squamous NSCLC with PDL-1 expression available and \>1% by IHC (as defined by the Pembrolizumab companion diagnostic test, determined by appropriate local pathology lab. * No previous treatment with check-point inhibitor. Or patients with checkpoint inhibitor based treatment as last therapy before entering the trial. * Documented disease progression or relapse (based on investigator's assessment) during or after completion of at least 2 cycles of platinum-based chemotherapy as first line treatment of Stage IIIB/IV non- squamous NSCLC or for checkpoint inhibitor experienced patients during or after completion of at least 2 cycles of platinum-based chemotherapy and a checkpoint inhibitor treatment (monotherapy or in combination with chemotherapy). This includes patients relapsing within 6 months of completing (neo)adjuvant/curative-intent chemotherapy/CPI or chemoradiotherapy * At least one target lesion (outside the brain) that can be accurately measured per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 . * Lesion with a diameter ≥ 2cm assessed by radiologist as suitable for DCE-MRI evaluation (Mandatory in Part 1, optional in Part 2) * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Life expectancy ≥ 3 months after start of the treatment in the opinion of the investigator * Recovery from all reversible adverse events of previous anti-cancer therapies to baseline or CTCAE grade 1, except for alopecia (any grade), sensory peripheral neuropathy , must be ≤ CTCAE grade 2 or considered not clinically significant. * Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial * Availability and willingness to provide a fresh tumour tissue sample obtained at baseline, and after 2 cycles of treatment * Adequate organ function defined as all of the following (all screening labs should be performed at local lab within 10 days prior to treatment initiation) * Male or female patients. Women of childbearing potential (WOCBP)1 and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly, starting with the screening visit and through 6 months after the last dose of BI 836880 and BI 754091 treatment, respectively. A list of contraception methods meeting these criteria is provided in the patient information Note: Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to taking study medication during the screening period. At the following visits according to the flowchart a urine and/or serum pregnancy test is required. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patient to be eligible. Part 2: * Of full age (according to local legislation, usually ≥ 18 years) at screening * At least one measurable target lesion outside the brain (excluding the glioblastoma patients where brain lesions are allowed), that can be accurately measured per RECIST version 1.1 or Response Assessment in Neuro-Oncology (RANO) * ECOG performance status ≤ 1 (For glioblastoma cohort Karnofsky status is applicable) * Adequate organ function as all of the following (all screening labs should be performed at local lab within approximately 72 hours prior to treatment initiation) * Availability and willingness to provide a fresh tumor tissue sample obtained after relapse or progression on or after prior therapy. For Part 2, In case a fresh biopsy cannot be obtained (e.g. inaccessible lesions or patient safety concern), an archived specimen obtained up to 6 months prior to cycle 1, visit 1 (C1V1) may be submitted in case no systemic antineoplastic therapy has been administered between the biopsy and C1V1 (except for cohort D). For cohorts E, F and G, a fresh on-treatment biopsy is mandatory at C3D1, if possible from the same lesion as the pre-treatment biopsy. * Life expectancy ≥ 3 months after start of the treatment in the opinion of the investigator * Recovery from all reversible adverse events of previous anti-cancer therapies to baseline or CTCAE grade 1, except for alopecia (any grade), sensory peripheral neuropathy , must be ≤ CTCAE grade 2 or considered not clinically significant. * Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial * Male or female patients. Women of childbearing potential (WOCBP)2 and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly, for the entire duration of the trial treatment intake and for 6 months after the end of the trial treatment. A list of contraception methods meeting these criteria is provided in the patient information. Note: Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours during the screening period. At the following visits according to the flowchart, a urine and/or serum pregnancy test is required. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patient to be eligible.- Further inclusion criteria apply
Exclusion criteria
Part 1: * Known hypersensitivity to the trial drugs or their excipients or risk of allergic of anaphylactic reaction to drug product according to Investigator judgement (e.g. patient with history of anaphylactic reaction or autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids, or the equivalent of \</= 10 mg/day prednisone). * Known immunodeficiency virus infection or an active hepatitis B or C virus infection. * History of severe hypersensitivity reactions to other mAbs. * Immunosuppressive corticosteroid doses (\> 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of trial medication. * Current or prior treatment with any systemic anti-cancer therapy either within 28 days or a minimum of 5 half-lives, whichever is shorter before start of treatment. * Serious concomitant disease, especially those affecting compliance with trial requirements or which are considered relevant for the evaluation of the endpoints of the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers (gastrointestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the investigator would make the patient inappropriate for entry into the trial. * Major injuries and/or surgery or bone fracture within 4 weeks of start of treatment, or planned surgical procedures during the trial period. * Patients with personal or family history of QT prolongation and/or long QT syndrome, or prolonged QTcF at baseline (\> 480 ms). * Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure \> NYHA II). Uncontrolled hypertension defined as: Blood pressure in rested and relaxed condition \>= 140 mmHg, systolic or \>= 90 mmHg diastolic (with or without medication), measured according to Appendix 10.2. * LVEF \< 50% * History of severe hemorrhagic or thromboembolic event in the past 12 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis). * Known inherited predisposition to bleeding or to thrombosis in the opinion of the investigator. * Patient with brain metastases that are symptomatic and/or require therapy. * Patients who require full-dose anticoagulation (according to local guidelines). No Vitamin K antagonist and other anticoagulation allowed; LMWH allowed only for prevention not for curative treatment. * History of pneumonitis within the last 5 years * Patients who are under judicial protection and patients who are legally institutionalized. * Patients unable or unwilling to comply with protocol * Previous enrolment in this trial (Part 1 or Part 2). * Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial. * Women who are pregnant, nursing, or who plan to become pregnant in the trial Part 2: * Known hypersensitivity to the trial drugs or their excipients or risk of allergic of anaphylactic reaction to drug product according to Investigator judgement (e.g. patient with history of anaphylactic reaction or autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids, or the equivalent of \</= 10 mg/day prednisone). * Not more than one CPI based treatment regimen prior to entering study (e.g. anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T lymphocyte associated antigen-4 (anti-CTLA-4) antibody). In case of CPIs combination, they need to be approved by the local regulatory agencies; for e.g., Melanoma cohort (Cohort E). * Known HIV infection * Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (exception for patients in HCC cohorts; Cohorts F& G). * History of severe hypersensitivity reactions to other mAbs. * Immunosuppressive corticosteroid doses (\> 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of trial medication except for control of cerebral edema in case of recurrent glioblastoma (cohort D). * Current or prior treatment with any systemic anti-cancer therapy (including radiotherapy) either within 28 days or a minimum of 5 half-lives, whichever is shorter before start of treatment * Serious concomitant disease, especially those affecting compliance with trial requirements or which are considered relevant for the evaluation of the endpoints of the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers (gastrointestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the investigator would make the patient inappropriate for entry into the trial. * Major injuries and/or surgery or bone fracture within 4 weeks of start of treatment, or planned surgical procedures during the trial period. * Patients with personal or family history of QT prolongation and/or long QT syndrome, or prolonged QTcF at baseline (\> 480 ms). * Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure \> NYHA II). Uncontrolled hypertension defined as: Blood pressure in rested and relaxed condition \>= 140 mmHg, systolic or \>= 90 mmHg diastolic (with or without medication), measured according to Appendix 10.2. * LVEF \< 50% * History of severe hemorrhagic or thromboembolic event in the past 12 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis). * Known inherited predisposition to bleeding or to thrombosis in the opinion of the investigator. * Patient with brain metastases that are symptomatic and/or require therapy. * Patients who require full-dose anticoagulation (according to local guidelines). * No Vitamin K antagonist and other anticoagulation allowed; LMWH allowed only for prevention not for curative treatment. * History of pneumonitis (non-infectious) within the last 5 years * Patients who are under judicial protection and patients who are legally institutionalized. * Patients unable or unwilling to comply with protocol * Previous enrolment in this trial. * Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial. * Women who are pregnant, nursing, or who plan to become pregnant in the trial * UncontrolledSymptomatic pleural effusion, pericardial effusion, or ascites * Prior treatment with any antiangiogenic treatment (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc) except for sorafenib and lenvatinib in 2nd line HCC cohort (Cohort F) * Has received a live vaccine within 30 days prior to the first dose of study drug * Patients with known active second malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast. Patients are not considered to have a currently active malignancy if they have completed anticancer therapy and have been disease free for greater than 2 years prior to screening * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 - Number of Patients With Dose Limiting Toxicity (DLT) Within the First Cycle of Treatment | The first treatment cycle, up to 21 days. | Number of patients with dose limiting toxicity (DLT) within the first cycle of treatment. |
| Part 2 - Objective Response (OR) | Up to 778 days. | Objective Response (OR) defined as best overall response (Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)) of complete response (CR) or partial response (PR) from first treatment infusion until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anticancer therapy, lost to follow-up, or withdrawal of consent. In case of recurrent glioblastoma (GBM), assessment will be based on RANO (Response Assessment in Neuro-Oncology) criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Up to 1263 days. | The number of patients with any drug related adverse events (AEs) leading to dose reduction or discontinuation. |
| Part 2 - Adverse Events (AEs) | Up to 778 days. | The number of patients with any adverse events (AEs). |
| Part 2 - Drug Related AEs | Up to 778 days. | The number of patients with any drug related adverse events (AEs). |
| Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Up to 778 days. | The number of patients with any drug related adverse events (AEs) leading to dose reduction or discontinuation. |
| Part 2 - Disease Control (DC) | Up to 778 days. | Disease control (DC), defined as best overall response of CR, PR, or stable disease (SD) (Response Assessment in Neuro-Oncology (RANO for GBM & RECIST1.1 for all other cohorts). |
| Part 2 - Duration of Objective Response (DoR) | Up to 84.4 weeks. | Duration of objective response (DoR), defined as the time from first documented CR or PR (RANO for GBM & RECIST1.1 for all other cohorts) until the earliest of disease progression or death among patients with OR. |
| Part 2 - Progression-free Survival (PFS) | Up to 778 days. | Progression-free survival (PFS) (RANO for GBM & RECIST1.1 for all other cohorts), defined as the time from first treatment infusion until disease progression or death from any cause, whichever occurs earlier. Tumour shrinkage (in millimeters), defined as the difference between the minimum post-baseline sum of diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) and the baseline sum of diameters of the same set of target lesions in case of RECIST. In GBM, using RANO criteria, tumor shrinkage will be calculated based on the difference between the post-baseline and baseline measurements of the sum of product of the largest bi-dimensional measurements for all target lesions. |
| Part 1 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle. | Part 1 - Maximum measured concentration of BI 836880 in plasma (Cmax) after the first infusion cycle. |
| Part 1 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the Fourth Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle. | Part 1 - Maximum measured concentration of BI 836880 in plasma (Cmax) after the fourth infusion cycle. |
| Part 1 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle. | Part 1 - Time from dosing to maximum serum concentration of BI 836880 (Tmax) after the first infusion cycle. |
| Part 1 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the Fourth Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle. | Part 1 - Time from dosing to maximum serum concentration of BI 836880 (Tmax) after the fourth infusion cycle. |
| Part 1 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle. | Part 1 - Area under the concentration-time curve of BI 836880 in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the first infusion cycle. |
| Part 1 - Adverse Events (AEs) | Up to 1263 days. | The number of patients with any adverse events (AEs). |
| Part 2 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle. | Part 2 - Maximum measured concentration of BI 836880 in plasma (Cmax) after the first infusion cycle. |
| Part 2 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle. | Part 2 - Time from dosing to maximum serum concentration of BI 836880 (Tmax) after the first infusion cycle. |
| Part 2 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle. | Part 2 - Area under the concentration-time curve of BI 836880 in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the first infusion cycle. |
| Part 1 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle. | Part 1 - Maximum measured concentration of ezabenlimab in plasma (Cmax) after the first infusion cycle. |
| Part 1 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the Fourth Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle. | Part 1 - Maximum measured concentration of ezabenlimab in plasma (Cmax) after the fourth infusion cycle. |
| Part 1 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle. | Part 1 - Time from dosing to maximum serum concentration of ezabenlimab (Tmax) after the first infusion cycle. |
| Part 1 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the Fourth Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle. | Part 1 - Time from dosing to maximum serum concentration of ezabenlimab (Tmax) after the fourth infusion cycle. |
| Part 1 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle. | Part 1 - Area under the concentration-time curve of ezabenlimab in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the first infusion cycle. |
| Part 1 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the Fourth Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle. | Part 1 - Area under the concentration-time curve of ezabenlimab in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the fourth infusion cycle. |
| Part 2 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle. | Part 2 - Maximum measured concentration of ezabenlimab in plasma (Cmax) after the first infusion cycle. |
| Part 2 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle. | Part 2 - Time from dosing to maximum serum concentration of ezabenlimab (Tmax) after the first infusion cycle. |
| Part 2 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle. | Part 2 - Area under the concentration-time curve of ezabenlimab in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the first infusion cycle. |
| Part 1 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the Fourth Infusion Cycle | 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle. | Part 1 - Area under the concentration-time curve of BI 836880 in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the fourth infusion cycle. |
| Part 1 - Drug Related AEs | Up to 1263 days. | The number of patients with any drug related adverse events (AEs). |
Countries
Australia, France, Germany, Hong Kong, Poland, Russia, South Korea, Spain, Taiwan, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
This was a non-randomised, uncontrolled, open-label, dose escalating trial of BI 836880 administered in combination with ezabenlimab intravenously every 3 weeks. The trial consisted of 2 parts: Part 1 (dose escalation of BI 836880 in combination with ezabenlimab) and Part 2 (expansion phase in 8 cohorts).
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 - BI 836880 360 mg Patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who progressed during or after first line platinum-based chemotherapy, received 360 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles. | 3 |
| Part 1 - BI 836880 500 mg Patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who progressed during or after first line platinum-based chemotherapy, received 500 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles. | 3 |
| Part 1 - BI 836880 720 mg Patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who progressed during or after first line platinum-based chemotherapy, received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles. | 8 |
| Part 2 - Cohort A, 2nd Line NSCLC Patient with pathologically confirmed locally advanced or metastatic non-squamous NSCLC who progressed during or after check-point inhibitor monotherapy treatment. Patient must also have received treatment with a platinum-based chemotherapy regimen and have progressed or be intolerant, or ineligible, as per applicable local practice. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles. | 42 |
| Part 2 - Cohort B, 3rd Line NSCLC Patient with pathologically confirmed locally advanced or metastatic non-squamous NSCLC who progressed during or after platinum-based chemotherapy and a check-point inhibitor (CPI) combination treatment as the most recent anticancer treatment. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles. | 40 |
| Part 2 - Cohort C, SCLC Patient with pathologically confirmed locally advanced or metastatic Small Cell Lung Cancer (SCLC) with documented intolerance to platinum-based chemotherapy or refractory to platinum-based chemotherapy. Patients who were platinumsensitive must also have received one additional prior line of platinum-based chemotherapy, if eligible, with or without combination with CPI as per applicable local treatment country guidelines. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles. | 31 |
| Part 2 - Cohort D, Glioblastoma Patient with histologically confirmed recurrent glioblastoma with no more than two previous lines of chemotherapy. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles. | 31 |
| Part 2 - Cohort E, Melanoma Patient with histologically confirmed, unresectable, Stage IV metastatic melanoma who progressed during or after CPI based regimen. Patients with a BRAF mutation must have received targeted treatment, or were not eligible, with a BRAF and MEK inhibitor as per applicable local country guidelines. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles. | 32 |
| Part 2 - Cohort F, 2nd Line Hepatocellular Carcinoma Patient with locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC) who were intolerant or progressed during 1st line sorafenib or lenvatinib treatment. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles. | 30 |
| Part 2 - Cohort G, 1st Line Hepatocellular Carcinoma (HCC) Patient with locally advanced or metastatic and/or unresectable HCC with no prior systemic treatment. This will be implemented only in countries where this cohort is approved. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles. | 31 |
| Part 2 - Cohort H, 2nd Line HCC - Atezolizumab in Combination With Bevacizumab Failures Patient with locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC) who were intolerant or progressed during 1st line treatment with atezolizumab in combination with bevacizumab. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles. | 1 |
| Total | 252 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Dose Limiting Toxicity (DLT) | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | missing reason | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other adverse event or clinical progression | 0 | 1 | 3 | 14 | 10 | 8 | 5 | 4 | 6 | 11 | 0 |
| Overall Study | Other than listed | 0 | 1 | 0 | 0 | 2 | 2 | 0 | 0 | 4 | 4 | 1 |
| Overall Study | Progressive disease | 3 | 0 | 4 | 20 | 23 | 15 | 24 | 27 | 13 | 13 | 0 |
| Overall Study | Refused to continue taking trial medication | 0 | 0 | 0 | 2 | 0 | 3 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1 - BI 836880 360 mg | Part 1 - BI 836880 500 mg | Part 1 - BI 836880 720 mg | Part 2 - Cohort A, 2nd Line NSCLC | Part 2 - Cohort B, 3rd Line NSCLC | Part 2 - Cohort C, SCLC | Part 2 - Cohort D, Glioblastoma | Part 2 - Cohort E, Melanoma | Part 2 - Cohort F, 2nd Line Hepatocellular Carcinoma | Part 2 - Cohort G, 1st Line Hepatocellular Carcinoma (HCC) | Part 2 - Cohort H, 2nd Line HCC - Atezolizumab in Combination With Bevacizumab Failures | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 56.3 Years STANDARD_DEVIATION 9.5 | 60.3 Years STANDARD_DEVIATION 2.1 | 58.3 Years STANDARD_DEVIATION 12.1 | 64.3 Years STANDARD_DEVIATION 9.1 | 59.2 Years STANDARD_DEVIATION 10.1 | 63.1 Years STANDARD_DEVIATION 11.7 | 56.7 Years STANDARD_DEVIATION 9.5 | 59.9 Years STANDARD_DEVIATION 14.7 | 64.4 Years STANDARD_DEVIATION 8.8 | 63.6 Years STANDARD_DEVIATION 9.4 | 55 Years | 61.4 Years STANDARD_DEVIATION 10.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 5 Participants | 29 Participants | 17 Participants | 25 Participants | 26 Participants | 15 Participants | 20 Participants | 31 Participants | 1 Participants | 172 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants | 13 Participants | 23 Participants | 5 Participants | 4 Participants | 16 Participants | 10 Participants | 0 Participants | 0 Participants | 77 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 10 Participants | 3 Participants | 4 Participants | 6 Participants | 4 Participants | 8 Participants | 4 Participants | 0 Participants | 39 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants | 13 Participants | 23 Participants | 3 Participants | 4 Participants | 16 Participants | 10 Participants | 0 Participants | 0 Participants | 75 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 5 Participants | 19 Participants | 14 Participants | 24 Participants | 20 Participants | 12 Participants | 12 Participants | 25 Participants | 1 Participants | 135 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 3 Participants | 15 Participants | 18 Participants | 10 Participants | 10 Participants | 10 Participants | 4 Participants | 7 Participants | 1 Participants | 80 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 5 Participants | 27 Participants | 22 Participants | 21 Participants | 21 Participants | 22 Participants | 26 Participants | 24 Participants | 0 Participants | 172 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 1 / 3 | 1 / 8 | 4 / 42 | 2 / 40 | 5 / 31 | 1 / 31 | 2 / 32 | 4 / 30 | 5 / 31 | 0 / 1 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 8 / 8 | 36 / 42 | 35 / 40 | 23 / 31 | 28 / 31 | 30 / 32 | 28 / 30 | 27 / 31 | 1 / 1 |
| serious Total, serious adverse events | 2 / 3 | 3 / 3 | 6 / 8 | 24 / 42 | 21 / 40 | 14 / 31 | 10 / 31 | 11 / 32 | 16 / 30 | 17 / 31 | 0 / 1 |
Outcome results
Primary
Part 1 - Number of Patients With Dose Limiting Toxicity (DLT) Within the First Cycle of Treatment
Number of patients with dose limiting toxicity (DLT) within the first cycle of treatment.
Time frame: The first treatment cycle, up to 21 days.
Population: Maximum tolerated dose (MTD) set: This patient set includes all patients enrolled in dose escalation and confirmation of MTD cohort of the trial (Part 1) who were documented to have received at least one dose of ezabenlimab or BI 836880 and were evaluable for the MTD determination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 - BI 836880 360 mg | Part 1 - Number of Patients With Dose Limiting Toxicity (DLT) Within the First Cycle of Treatment | 1 Participants |
| Part 1 - BI 836880 500 mg | Part 1 - Number of Patients With Dose Limiting Toxicity (DLT) Within the First Cycle of Treatment | 0 Participants |
| Part 1 - BI 836880 720 mg | Part 1 - Number of Patients With Dose Limiting Toxicity (DLT) Within the First Cycle of Treatment | 0 Participants |
| Part 1 - total | Part 1 - Number of Patients With Dose Limiting Toxicity (DLT) Within the First Cycle of Treatment | 1 Participants |
Primary
Part 2 - Objective Response (OR)
Objective Response (OR) defined as best overall response (Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)) of complete response (CR) or partial response (PR) from first treatment infusion until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anticancer therapy, lost to follow-up, or withdrawal of consent. In case of recurrent glioblastoma (GBM), assessment will be based on RANO (Response Assessment in Neuro-Oncology) criteria.
Time frame: Up to 778 days.
Population: All patients enrolled in part 2 of the trial who were documented to have received at least one dose of ezabenlimab or BI 836880.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 - BI 836880 360 mg | Part 2 - Objective Response (OR) | 7 Participants |
| Part 1 - BI 836880 500 mg | Part 2 - Objective Response (OR) | 3 Participants |
| Part 1 - BI 836880 720 mg | Part 2 - Objective Response (OR) | 6 Participants |
| Part 1 - total | Part 2 - Objective Response (OR) | 7 Participants |
| Part 2 - Cohort E, Melanoma | Part 2 - Objective Response (OR) | 2 Participants |
| Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma | Part 2 - Objective Response (OR) | 12 Participants |
| Part 2 - Cohort G, 1st line Hepatocellular Carcinoma | Part 2 - Objective Response (OR) | 8 Participants |
| Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures | Part 2 - Objective Response (OR) | 0 Participants |
| Part 2 - total | Part 2 - Objective Response (OR) | 45 Participants |
Secondary
Part 1 - Adverse Events (AEs)
The number of patients with any adverse events (AEs).
Time frame: Up to 1263 days.
Population: All patients enrolled in part 1 of the trial who were documented to have received at least one dose of ezabenlimab or BI 836880.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 - BI 836880 360 mg | Part 1 - Adverse Events (AEs) | 3 Participants |
| Part 1 - BI 836880 500 mg | Part 1 - Adverse Events (AEs) | 3 Participants |
| Part 1 - BI 836880 720 mg | Part 1 - Adverse Events (AEs) | 8 Participants |
| Part 1 - total | Part 1 - Adverse Events (AEs) | 14 Participants |
Secondary
Part 1 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle
Part 1 - Area under the concentration-time curve of BI 836880 in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Population: PK analysis set (PKS) part 1: This patient set included all patients in part 1 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 500 mg | Part 1 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 19200 hours*microgram/milliliter | Geometric Coefficient of Variation 28.5 |
| Part 1 - BI 836880 720 mg | Part 1 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 35100 hours*microgram/milliliter | Geometric Coefficient of Variation 20.9 |
Secondary
Part 1 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the Fourth Infusion Cycle
Part 1 - Area under the concentration-time curve of BI 836880 in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the fourth infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle.
Population: PK analysis set (PKS) part 1: This patient set included all patients in part 1 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 500 mg | Part 1 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the Fourth Infusion Cycle | NA hours*microgram/milliliter | — |
| Part 1 - BI 836880 720 mg | Part 1 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the Fourth Infusion Cycle | 59700 hours*microgram/milliliter | Geometric Coefficient of Variation 14.2 |
Secondary
Part 1 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle
Part 1 - Area under the concentration-time curve of ezabenlimab in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Population: PK analysis set (PKS) part 1: This patient set included all patients in part 1 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 360 mg | Part 1 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 15100 hours*microgram/milliliter | Geometric Coefficient of Variation 42 |
| Part 1 - BI 836880 500 mg | Part 1 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 15800 hours*microgram/milliliter | Geometric Coefficient of Variation 8.13 |
| Part 1 - BI 836880 720 mg | Part 1 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 14900 hours*microgram/milliliter | Geometric Coefficient of Variation 27.5 |
Secondary
Part 1 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the Fourth Infusion Cycle
Part 1 - Area under the concentration-time curve of ezabenlimab in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the fourth infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle.
Population: PK analysis set (PKS) part 1: This patient set included all patients in part 1 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 360 mg | Part 1 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the Fourth Infusion Cycle | NA hours*microgram/milliliter | — |
| Part 1 - BI 836880 500 mg | Part 1 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the Fourth Infusion Cycle | 34000 hours*microgram/milliliter | Geometric Coefficient of Variation 17.8 |
| Part 1 - BI 836880 720 mg | Part 1 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the Fourth Infusion Cycle | 25200 hours*microgram/milliliter | Geometric Coefficient of Variation 32.5 |
Secondary
Part 1 - Drug Related AEs
The number of patients with any drug related adverse events (AEs).
Time frame: Up to 1263 days.
Population: All patients enrolled in part 1 of the trial who were documented to have received at least one dose of ezabenlimab or BI 836880.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 - BI 836880 360 mg | Part 1 - Drug Related AEs | 3 Participants |
| Part 1 - BI 836880 500 mg | Part 1 - Drug Related AEs | 2 Participants |
| Part 1 - BI 836880 720 mg | Part 1 - Drug Related AEs | 7 Participants |
| Part 1 - total | Part 1 - Drug Related AEs | 12 Participants |
Secondary
Part 1 - Drug Related AEs Leading to Dose Reduction or Discontinuation
The number of patients with any drug related adverse events (AEs) leading to dose reduction or discontinuation.
Time frame: Up to 1263 days.
Population: All patients enrolled in part 1 of the trial who were documented to have received at least one dose of ezabenlimab or BI 836880.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 - BI 836880 360 mg | Part 1 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to dose reduction of trial drug | 0 Participants |
| Part 1 - BI 836880 360 mg | Part 1 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to discontinuation of trial drug | 1 Participants |
| Part 1 - BI 836880 500 mg | Part 1 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to discontinuation of trial drug | 1 Participants |
| Part 1 - BI 836880 500 mg | Part 1 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to dose reduction of trial drug | 0 Participants |
| Part 1 - BI 836880 720 mg | Part 1 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to dose reduction of trial drug | 0 Participants |
| Part 1 - BI 836880 720 mg | Part 1 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to discontinuation of trial drug | 2 Participants |
| Part 1 - total | Part 1 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to dose reduction of trial drug | 0 Participants |
| Part 1 - total | Part 1 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to discontinuation of trial drug | 4 Participants |
Secondary
Part 1 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle
Part 1 - Maximum measured concentration of BI 836880 in plasma (Cmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Population: PK analysis set (PKS) part 1: This patient set included all patients in part 1 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 500 mg | Part 1 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle | NA microgram/milliliter | — |
| Part 1 - BI 836880 720 mg | Part 1 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle | 175 microgram/milliliter | Geometric Coefficient of Variation 21.4 |
Secondary
Part 1 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the Fourth Infusion Cycle
Part 1 - Maximum measured concentration of BI 836880 in plasma (Cmax) after the fourth infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle.
Population: PK analysis set (PKS) part 1: This patient set included all patients in part 1 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 500 mg | Part 1 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the Fourth Infusion Cycle | NA microgram/milliliter | — |
| Part 1 - BI 836880 720 mg | Part 1 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the Fourth Infusion Cycle | 273 microgram/milliliter | Geometric Coefficient of Variation 20.9 |
Secondary
Part 1 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle
Part 1 - Maximum measured concentration of ezabenlimab in plasma (Cmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Population: PK analysis set (PKS) part 1: This patient set included all patients in part 1 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 360 mg | Part 1 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle | 80.7 microgram/milliliter | Geometric Coefficient of Variation 24.8 |
| Part 1 - BI 836880 500 mg | Part 1 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle | 144 microgram/milliliter | Geometric Coefficient of Variation 78.9 |
| Part 1 - BI 836880 720 mg | Part 1 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle | 75.8 microgram/milliliter | Geometric Coefficient of Variation 25.3 |
Secondary
Part 1 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the Fourth Infusion Cycle
Part 1 - Maximum measured concentration of ezabenlimab in plasma (Cmax) after the fourth infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle.
Population: PK analysis set (PKS) part 1: This patient set included all patients in part 1 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 360 mg | Part 1 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the Fourth Infusion Cycle | NA microgram/milliliter | — |
| Part 1 - BI 836880 500 mg | Part 1 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the Fourth Infusion Cycle | 131 microgram/milliliter | Geometric Coefficient of Variation 16.2 |
| Part 1 - BI 836880 720 mg | Part 1 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the Fourth Infusion Cycle | 106 microgram/milliliter | Geometric Coefficient of Variation 20.4 |
Secondary
Part 1 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle
Part 1 - Time from dosing to maximum serum concentration of BI 836880 (Tmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Population: PK analysis set (PKS) part 1: This patient set included all patients in part 1 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 500 mg | Part 1 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle | NA hours | — |
| Part 1 - BI 836880 720 mg | Part 1 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle | 1.84 hours | Geometric Coefficient of Variation 134 |
Secondary
Part 1 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the Fourth Infusion Cycle
Part 1 - Time from dosing to maximum serum concentration of BI 836880 (Tmax) after the fourth infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle.
Population: PK analysis set (PKS) part 1: This patient set included all patients in part 1 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 500 mg | Part 1 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the Fourth Infusion Cycle | NA hours | — |
| Part 1 - BI 836880 720 mg | Part 1 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the Fourth Infusion Cycle | 3.29 hours | Geometric Coefficient of Variation 91.9 |
Secondary
Part 1 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle
Part 1 - Time from dosing to maximum serum concentration of ezabenlimab (Tmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Population: PK analysis set (PKS) part 1: This patient set included all patients in part 1 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 360 mg | Part 1 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle | 1.83 hours | Geometric Coefficient of Variation 137 |
| Part 1 - BI 836880 500 mg | Part 1 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle | 1.06 hours | Geometric Coefficient of Variation 7.84 |
| Part 1 - BI 836880 720 mg | Part 1 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle | 2.79 hours | Geometric Coefficient of Variation 101 |
Secondary
Part 1 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the Fourth Infusion Cycle
Part 1 - Time from dosing to maximum serum concentration of ezabenlimab (Tmax) after the fourth infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle.
Population: PK analysis set (PKS) part 1: This patient set included all patients in part 1 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 360 mg | Part 1 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the Fourth Infusion Cycle | NA hours | — |
| Part 1 - BI 836880 500 mg | Part 1 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the Fourth Infusion Cycle | 1.55 hours | Geometric Coefficient of Variation 65.5 |
| Part 1 - BI 836880 720 mg | Part 1 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the Fourth Infusion Cycle | 2.32 hours | Geometric Coefficient of Variation 55.6 |
Secondary
Part 2 - Adverse Events (AEs)
The number of patients with any adverse events (AEs).
Time frame: Up to 778 days.
Population: All patients enrolled in part 2 of the trial who were documented to have received at least one dose of ezabenlimab or BI 836880.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 - BI 836880 360 mg | Part 2 - Adverse Events (AEs) | 39 Participants |
| Part 1 - BI 836880 500 mg | Part 2 - Adverse Events (AEs) | 39 Participants |
| Part 1 - BI 836880 720 mg | Part 2 - Adverse Events (AEs) | 27 Participants |
| Part 1 - total | Part 2 - Adverse Events (AEs) | 30 Participants |
| Part 2 - Cohort E, Melanoma | Part 2 - Adverse Events (AEs) | 31 Participants |
| Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma | Part 2 - Adverse Events (AEs) | 28 Participants |
| Part 2 - Cohort G, 1st line Hepatocellular Carcinoma | Part 2 - Adverse Events (AEs) | 28 Participants |
| Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures | Part 2 - Adverse Events (AEs) | 1 Participants |
| Part 2 - total | Part 2 - Adverse Events (AEs) | 223 Participants |
Secondary
Part 2 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle
Part 2 - Area under the concentration-time curve of BI 836880 in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Population: PK analysis set (PKS) part 2: This patient set included all patients in part 2 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 360 mg | Part 2 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 44000 hours*microgram/milliliter | Geometric Coefficient of Variation 28.2 |
| Part 1 - BI 836880 500 mg | Part 2 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 41300 hours*microgram/milliliter | Geometric Coefficient of Variation 31.1 |
| Part 1 - BI 836880 720 mg | Part 2 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 42000 hours*microgram/milliliter | Geometric Coefficient of Variation 11.1 |
| Part 1 - total | Part 2 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 44900 hours*microgram/milliliter | Geometric Coefficient of Variation 22.4 |
| Part 2 - Cohort E, Melanoma | Part 2 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 38000 hours*microgram/milliliter | Geometric Coefficient of Variation 23.8 |
| Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma | Part 2 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 39400 hours*microgram/milliliter | Geometric Coefficient of Variation 21.4 |
| Part 2 - Cohort G, 1st line Hepatocellular Carcinoma | Part 2 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 36600 hours*microgram/milliliter | Geometric Coefficient of Variation 25.2 |
| Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures | Part 2 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | NA hours*microgram/milliliter | — |
Secondary
Part 2 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle
Part 2 - Area under the concentration-time curve of ezabenlimab in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Population: PK analysis set (PKS) part 2: This patient set included all patients in part 2 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 360 mg | Part 2 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 17600 hours*microgram/milliliter | Geometric Coefficient of Variation 29.7 |
| Part 1 - BI 836880 500 mg | Part 2 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 15200 hours*microgram/milliliter | Geometric Coefficient of Variation 35.2 |
| Part 1 - BI 836880 720 mg | Part 2 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 17700 hours*microgram/milliliter | Geometric Coefficient of Variation 16.9 |
| Part 1 - total | Part 2 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 19300 hours*microgram/milliliter | Geometric Coefficient of Variation 22.1 |
| Part 2 - Cohort E, Melanoma | Part 2 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 14500 hours*microgram/milliliter | Geometric Coefficient of Variation 25.5 |
| Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma | Part 2 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 14900 hours*microgram/milliliter | Geometric Coefficient of Variation 23.1 |
| Part 2 - Cohort G, 1st line Hepatocellular Carcinoma | Part 2 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | 14200 hours*microgram/milliliter | Geometric Coefficient of Variation 31.5 |
| Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures | Part 2 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle | NA hours*microgram/milliliter | — |
Secondary
Part 2 - Disease Control (DC)
Disease control (DC), defined as best overall response of CR, PR, or stable disease (SD) (Response Assessment in Neuro-Oncology (RANO for GBM & RECIST1.1 for all other cohorts).
Time frame: Up to 778 days.
Population: All patients enrolled in part 2 of the trial who were documented to have received at least one dose of ezabenlimab or BI 836880.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 - BI 836880 360 mg | Part 2 - Disease Control (DC) | 34 Participants |
| Part 1 - BI 836880 500 mg | Part 2 - Disease Control (DC) | 25 Participants |
| Part 1 - BI 836880 720 mg | Part 2 - Disease Control (DC) | 12 Participants |
| Part 1 - total | Part 2 - Disease Control (DC) | 25 Participants |
| Part 2 - Cohort E, Melanoma | Part 2 - Disease Control (DC) | 18 Participants |
| Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma | Part 2 - Disease Control (DC) | 24 Participants |
| Part 2 - Cohort G, 1st line Hepatocellular Carcinoma | Part 2 - Disease Control (DC) | 25 Participants |
| Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures | Part 2 - Disease Control (DC) | 1 Participants |
| Part 2 - total | Part 2 - Disease Control (DC) | 164 Participants |
Secondary
Part 2 - Drug Related AEs
The number of patients with any drug related adverse events (AEs).
Time frame: Up to 778 days.
Population: All patients enrolled in part 2 of the trial who were documented to have received at least one dose of ezabenlimab or BI 836880.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 - BI 836880 360 mg | Part 2 - Drug Related AEs | 27 Participants |
| Part 1 - BI 836880 500 mg | Part 2 - Drug Related AEs | 27 Participants |
| Part 1 - BI 836880 720 mg | Part 2 - Drug Related AEs | 16 Participants |
| Part 1 - total | Part 2 - Drug Related AEs | 24 Participants |
| Part 2 - Cohort E, Melanoma | Part 2 - Drug Related AEs | 18 Participants |
| Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma | Part 2 - Drug Related AEs | 27 Participants |
| Part 2 - Cohort G, 1st line Hepatocellular Carcinoma | Part 2 - Drug Related AEs | 20 Participants |
| Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures | Part 2 - Drug Related AEs | 1 Participants |
| Part 2 - total | Part 2 - Drug Related AEs | 160 Participants |
Secondary
Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation
The number of patients with any drug related adverse events (AEs) leading to dose reduction or discontinuation.
Time frame: Up to 778 days.
Population: All patients enrolled in part 2 of the trial who were documented to have received at least one dose of ezabenlimab or BI 836880.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 - BI 836880 360 mg | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to dose reduction of trial drug | 1 Participants |
| Part 1 - BI 836880 360 mg | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to discontinuation of trial drug | 13 Participants |
| Part 1 - BI 836880 500 mg | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to discontinuation of trial drug | 4 Participants |
| Part 1 - BI 836880 500 mg | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to dose reduction of trial drug | 0 Participants |
| Part 1 - BI 836880 720 mg | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to discontinuation of trial drug | 6 Participants |
| Part 1 - BI 836880 720 mg | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to dose reduction of trial drug | 0 Participants |
| Part 1 - total | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to dose reduction of trial drug | 0 Participants |
| Part 1 - total | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to discontinuation of trial drug | 2 Participants |
| Part 2 - Cohort E, Melanoma | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to discontinuation of trial drug | 2 Participants |
| Part 2 - Cohort E, Melanoma | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to dose reduction of trial drug | 0 Participants |
| Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to discontinuation of trial drug | 5 Participants |
| Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to dose reduction of trial drug | 2 Participants |
| Part 2 - Cohort G, 1st line Hepatocellular Carcinoma | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to dose reduction of trial drug | 0 Participants |
| Part 2 - Cohort G, 1st line Hepatocellular Carcinoma | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to discontinuation of trial drug | 6 Participants |
| Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to dose reduction of trial drug | 0 Participants |
| Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to discontinuation of trial drug | 0 Participants |
| Part 2 - total | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to discontinuation of trial drug | 38 Participants |
| Part 2 - total | Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation | Subjects with AEs leading to dose reduction of trial drug | 3 Participants |
Secondary
Part 2 - Duration of Objective Response (DoR)
Duration of objective response (DoR), defined as the time from first documented CR or PR (RANO for GBM & RECIST1.1 for all other cohorts) until the earliest of disease progression or death among patients with OR.
Time frame: Up to 84.4 weeks.
Population: All patients with an objective response enrolled in part 2 of the trial who were documented to have received at least one dose of ezabenlimab or BI 836880.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 - BI 836880 360 mg | Part 2 - Duration of Objective Response (DoR) | 23.4 weeks |
| Part 1 - BI 836880 500 mg | Part 2 - Duration of Objective Response (DoR) | 54.0 weeks |
| Part 1 - BI 836880 720 mg | Part 2 - Duration of Objective Response (DoR) | 30.0 weeks |
| Part 1 - total | Part 2 - Duration of Objective Response (DoR) | 18.1 weeks |
| Part 2 - Cohort E, Melanoma | Part 2 - Duration of Objective Response (DoR) | 43.3 weeks |
| Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma | Part 2 - Duration of Objective Response (DoR) | 53.8 weeks |
| Part 2 - Cohort G, 1st line Hepatocellular Carcinoma | Part 2 - Duration of Objective Response (DoR) | 48.9 weeks |
| Part 2 - total | Part 2 - Duration of Objective Response (DoR) | 48.3 weeks |
Secondary
Part 2 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle
Part 2 - Maximum measured concentration of BI 836880 in plasma (Cmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Population: PK analysis set (PKS) part 2: This patient set included all patients in part 2 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 360 mg | Part 2 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle | 251 microgram/milliliter | Geometric Coefficient of Variation 25.5 |
| Part 1 - BI 836880 500 mg | Part 2 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle | 239 microgram/milliliter | Geometric Coefficient of Variation 30.5 |
| Part 1 - BI 836880 720 mg | Part 2 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle | 275 microgram/milliliter | Geometric Coefficient of Variation 39.8 |
| Part 1 - total | Part 2 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle | 253 microgram/milliliter | Geometric Coefficient of Variation 23.4 |
| Part 2 - Cohort E, Melanoma | Part 2 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle | 240 microgram/milliliter | Geometric Coefficient of Variation 27.2 |
| Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma | Part 2 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle | 214 microgram/milliliter | Geometric Coefficient of Variation 20.5 |
| Part 2 - Cohort G, 1st line Hepatocellular Carcinoma | Part 2 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle | 206 microgram/milliliter | Geometric Coefficient of Variation 31.7 |
| Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures | Part 2 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle | NA microgram/milliliter | — |
Secondary
Part 2 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle
Part 2 - Maximum measured concentration of ezabenlimab in plasma (Cmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Population: PK analysis set (PKS) part 2: This patient set included all patients in part 2 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 360 mg | Part 2 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle | 85.7 microgram/milliliter | Geometric Coefficient of Variation 26.3 |
| Part 1 - BI 836880 500 mg | Part 2 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle | 80.5 microgram/milliliter | Geometric Coefficient of Variation 22 |
| Part 1 - BI 836880 720 mg | Part 2 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle | 89.3 microgram/milliliter | Geometric Coefficient of Variation 27.8 |
| Part 1 - total | Part 2 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle | 87.7 microgram/milliliter | Geometric Coefficient of Variation 22.3 |
| Part 2 - Cohort E, Melanoma | Part 2 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle | 76.6 microgram/milliliter | Geometric Coefficient of Variation 18.2 |
| Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma | Part 2 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle | 74.6 microgram/milliliter | Geometric Coefficient of Variation 20.1 |
| Part 2 - Cohort G, 1st line Hepatocellular Carcinoma | Part 2 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle | 71.3 microgram/milliliter | Geometric Coefficient of Variation 28.3 |
| Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures | Part 2 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle | NA microgram/milliliter | — |
Secondary
Part 2 - Progression-free Survival (PFS)
Progression-free survival (PFS) (RANO for GBM & RECIST1.1 for all other cohorts), defined as the time from first treatment infusion until disease progression or death from any cause, whichever occurs earlier. Tumour shrinkage (in millimeters), defined as the difference between the minimum post-baseline sum of diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) and the baseline sum of diameters of the same set of target lesions in case of RECIST. In GBM, using RANO criteria, tumor shrinkage will be calculated based on the difference between the post-baseline and baseline measurements of the sum of product of the largest bi-dimensional measurements for all target lesions.
Time frame: Up to 778 days.
Population: All patients enrolled in part 2 of the trial who were documented to have received at least one dose of ezabenlimab or BI 836880.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 - BI 836880 360 mg | Part 2 - Progression-free Survival (PFS) | 43.14 weeks |
| Part 1 - BI 836880 500 mg | Part 2 - Progression-free Survival (PFS) | 20.43 weeks |
| Part 1 - BI 836880 720 mg | Part 2 - Progression-free Survival (PFS) | 6.29 weeks |
| Part 1 - total | Part 2 - Progression-free Survival (PFS) | 16.43 weeks |
| Part 2 - Cohort E, Melanoma | Part 2 - Progression-free Survival (PFS) | 27.86 weeks |
| Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma | Part 2 - Progression-free Survival (PFS) | 78.14 weeks |
| Part 2 - Cohort G, 1st line Hepatocellular Carcinoma | Part 2 - Progression-free Survival (PFS) | 37.00 weeks |
| Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures | Part 2 - Progression-free Survival (PFS) | 17.86 weeks |
| Part 2 - total | Part 2 - Progression-free Survival (PFS) | 28.00 weeks |
Secondary
Part 2 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle
Part 2 - Time from dosing to maximum serum concentration of BI 836880 (Tmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Population: PK analysis set (PKS) part 2: This patient set included all patients in part 2 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 360 mg | Part 2 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle | 2.75 hours | Geometric Coefficient of Variation 72 |
| Part 1 - BI 836880 500 mg | Part 2 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle | 2.61 hours | Geometric Coefficient of Variation 91.6 |
| Part 1 - BI 836880 720 mg | Part 2 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle | 2.25 hours | Geometric Coefficient of Variation 76.9 |
| Part 1 - total | Part 2 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle | 2.18 hours | Geometric Coefficient of Variation 73.9 |
| Part 2 - Cohort E, Melanoma | Part 2 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle | 2.47 hours | Geometric Coefficient of Variation 76.7 |
| Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma | Part 2 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle | 3.08 hours | Geometric Coefficient of Variation 109 |
| Part 2 - Cohort G, 1st line Hepatocellular Carcinoma | Part 2 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle | 2.54 hours | Geometric Coefficient of Variation 113 |
| Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures | Part 2 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle | NA hours | — |
Secondary
Part 2 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle
Part 2 - Time from dosing to maximum serum concentration of ezabenlimab (Tmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Population: PK analysis set (PKS) part 2: This patient set included all patients in part 2 of the trial in the treated set who provide at least one evaluable observation for at least one PK endpoint and no PK relevant protocol deviation. Only subjects with available data were included, subjects were excluded due to various reasons, e.g., sample time deviations, deviations in dose or dosing time or too high predose concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - BI 836880 360 mg | Part 2 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle | 2.93 hours | Geometric Coefficient of Variation 129 |
| Part 1 - BI 836880 500 mg | Part 2 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle | 2.90 hours | Geometric Coefficient of Variation 68.2 |
| Part 1 - BI 836880 720 mg | Part 2 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle | 2.26 hours | Geometric Coefficient of Variation 77.8 |
| Part 1 - total | Part 2 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle | 2.35 hours | Geometric Coefficient of Variation 84.8 |
| Part 2 - Cohort E, Melanoma | Part 2 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle | 3.03 hours | Geometric Coefficient of Variation 65.9 |
| Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma | Part 2 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle | 2.38 hours | Geometric Coefficient of Variation 63.8 |
| Part 2 - Cohort G, 1st line Hepatocellular Carcinoma | Part 2 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle | 2.75 hours | Geometric Coefficient of Variation 110 |
| Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures | Part 2 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle | NA hours | — |