An Open Label Phase Ib Dose Finding Study of BI 836880 in Combination With Ezabenlimab to Characterize Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy in Patients With Locally Advanced or Metastatic Non-squamous Non-Small Cell Lung Cancer and in Other Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 252
- 试验地点
- 43
- 主要终点
- Part 1 - Number of Patients With Dose Limiting Toxicity (DLT) Within the First Cycle of Treatment
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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:
- •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.
- •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
- •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).
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排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: BI 836880 (Drug)
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.
干预措施: Ezabenlimab (Drug)
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.
干预措施: BI 836880 (Drug)
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.
干预措施: Ezabenlimab (Drug)
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.
干预措施: BI 836880 (Drug)
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.
干预措施: Ezabenlimab (Drug)
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.
干预措施: BI 836880 (Drug)
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.
干预措施: Ezabenlimab (Drug)
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.
干预措施: BI 836880 (Drug)
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.
干预措施: Ezabenlimab (Drug)
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.
干预措施: BI 836880 (Drug)
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.
干预措施: Ezabenlimab (Drug)
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.
干预措施: BI 836880 (Drug)
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.
干预措施: Ezabenlimab (Drug)
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.
干预措施: BI 836880 (Drug)
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.
干预措施: Ezabenlimab (Drug)
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.
干预措施: BI 836880 (Drug)
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.
干预措施: Ezabenlimab (Drug)
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.
干预措施: BI 836880 (Drug)
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.
干预措施: Ezabenlimab (Drug)
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.
干预措施: BI 836880 (Drug)
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.
干预措施: Ezabenlimab (Drug)
结局指标
主要结局
Part 1 - Number of Patients With Dose Limiting Toxicity (DLT) Within the First Cycle of Treatment
时间窗: 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)
时间窗: 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.
次要结局
- Part 1 - Adverse Events (AEs)(Up to 1263 days.)
- Part 1 - Drug Related AEs(Up to 1263 days.)
- Part 1 - Drug Related AEs Leading to Dose Reduction or Discontinuation(Up to 1263 days.)
- Part 2 - Adverse Events (AEs)(Up to 778 days.)
- Part 2 - Drug Related AEs(Up to 778 days.)
- Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation(Up to 778 days.)
- Part 2 - Disease Control (DC)(Up to 778 days.)
- Part 2 - Duration of Objective Response (DoR)(Up to 84.4 weeks.)
- Part 2 - Progression-free Survival (PFS)(Up to 778 days.)
- 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 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 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 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 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 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 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 - 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 - 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 - 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 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 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 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 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 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 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 - 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 - 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.)