A Phase 1b/2, Open-Label, Randomized Study of Daratumumab Administered in Combination With Atezolizumab Compared With Atezolizumab Alone in Subjects With Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 100
- 主要终点
- Percentage of Participants With Overall Response Rate (ORR)
研究概览
简要总结
The purpose of the study is to compare the overall response rate (ORR) in non-small cell lung cancer (NSCLC) participants treated with daratumumab in combination with atezolizumab versus atezolizumab alone.
详细描述
This randomized (study medication assigned to participants by chance), multicenter study will provide study treatment (atezolizumab alone or atezolizumab+daratumumab) to participants with previously treated advanced or metastatic NSCLC to assess the anti-tumor activity and safety. Participants who receive atezolizumab treatment with confirmed disease progression based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be eligible to crossover to treatment (atezolizumab + daratumumab) if they meet crossover eligibility criteria. It is expected that 100 participants will enroll in the study including 6 participants in the safety run in phase. Data Monitoring Committee (DMC) will review ongoing data, and may formulate recommendations on study conduct, including expansion of enrollment of some PD-L1 subgroups, resulting in greater than 96 participants. The participants in the safety run in phase will be administered the combination of daratumumab and atezolizumab to determine the safety and tolerability that will be evaluated by the Safety Evaluation Team (SET) for dose limiting toxicity before the random assignment of participants in a 1:1 ratio in 2 treatment arms. The study consists of 3 phases: Screening Phase (up to 28 days), Treatment Phase and Post-Treatment Follow-up Phase which will continue until death, lost to follow-up, withdrawal of consent, or the End of the Study [the study end is approximately 6 to 12 months after that last participant is enrolled]. Participants will undergo tumor assessments (RECIST 1.1), immunogenicity, pharmacokinetics, biomarkers and safety evaluations (adverse events, laboratory tests, electrocardiogram [ECGs], vital sign measurements, physical examinations, Eastern Cooperative Oncology Group [ECOG] performance status score) over the time.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Have histologically or cytologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC) (Stage IIIb or greater)
- •Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- •Tumor cell programmed death-ligand 1 (PD-L1) score of tumor cells (TC)1-3 and immune cell PD-L1 score of tumor-infiltrating immune cells (IC)0-3 as determined by an immunohistochemistry (IHC) assay performed by the central laboratory on tissue obtained after the last line of therapy
- •A woman of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta- hCG]) at Screening within 14 days prior to study drug administration
- •Inclusion Criteria for Crossover:
- •Participants must have been randomized to Arm A of the study and had radiographic disease progression according to RECIST 1.1
- •Participants must have a mandatory biopsy at the time of disease progression according to RECIST 1.1 prior to crossing over. If not clinically feasible, discussion with Sponsor is required
- •The first dose of atezolizumab in the crossover arm should be within 42 days of last dose but no less than 21 days from the last dose prior to crossing over
排除标准
- •Received any of the following prescribed medications or therapies in the past:
- •Anti-cluster of differentiation(CD)38 therapy, including daratumumab
- •CD137 agonists, immune checkpoint inhibitors including but not limited to CTLA-4, anti-PD-1, and anti-PD-L1 therapies
- •Known to be seropositive for human immunodeficiency virus (HIV)
- •Prior allogeneic bone marrow transplantation or solid organ transplant
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- •Active hepatitis B, defined by a positive test for hepatitis B surface antigen [HBsAg] or prior history of hepatitis B, defined by presence of antibodies to hepatitis B core antigen [anti-HBc], regardless of hepatitis B surface antibody [anti-HBs] status; active hepatitis C or prior history of hepatitis C (anti-HCV positive), except in the setting of a sustained virologic response (SVR), defined as aviremia 12 weeks after completion of antiviral therapy. If hepatitis C virus (HCV) antibodies are detected, an HCV RNA test for viral load by polymerase chain reaction (PCR) should be performed at least 12 weeks after completion of antiviral therapy to rule out active infection
- •Exclusion Criteria for Crossover:
- •Received any subsequent anti-cancer therapies from the time between the last dose of atezolizumab prior to the first administration of study drug after crossing over
- •Whole brain radiation within 28 days or other radiotherapy within 14 days prior to first administration of study drug after crossing over
研究组 & 干预措施
Treatment Arm A: Atezolizumab
Participants in Treatment Arm A will receive Atezolizumab 1,200 milligram (mg) intravenously (IV) on Day 1 of every 21-day cycle. Participants with confirmed disease progression based on RECIST 1.1 may cross over to Arm B and receive daratumumab and atezolizumab, provided crossover eligibility criteria are met.
干预措施: Atezolizumab (Drug)
Treatment Arm B: Atezolizumab and Daratumumab
Participants will receive daratumumab 16 milligram per kilogram [mg/kg] (Safety Run-in and Treatment Arm B) Intravenously (IV) weekly for 3 cycles (Day 1, 8 and 15), and Day 1 of every 21-day cycle thereafter. Atezolizumab will be administered at 1200 mg IV on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter. Participants will continue to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria are met.
干预措施: Atezolizumab (Drug)
Treatment Arm B: Atezolizumab and Daratumumab
Participants will receive daratumumab 16 milligram per kilogram [mg/kg] (Safety Run-in and Treatment Arm B) Intravenously (IV) weekly for 3 cycles (Day 1, 8 and 15), and Day 1 of every 21-day cycle thereafter. Atezolizumab will be administered at 1200 mg IV on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter. Participants will continue to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria are met.
干预措施: Daratumumab (Drug)
结局指标
主要结局
Percentage of Participants With Overall Response Rate (ORR)
时间窗: Up to 1.5 years
ORR was defined as the percentage of participants with partial response (PR) or complete response (CR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Criteria for CR: Disappearance of all target lesions; all lymph nodes must be of non-pathological in size (less than \[\<\]10 millimeter \[mm\] short axis; normalization of tumor marker level. Criteria for PR: greater than or equal to (\>=)30 percent (%) decrease in sum of the diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions. Overall Response (OR) = CR + PR. The outcome measure (OM) was planned to be reported for participants based on their initial assignment to Randomized Phase: Atezolizumab'.
次要结局
- Number of Participants With Adverse Events(Up to 1.5 years)
- Duration of Response (DoR)(Up to 1.5 years)
- Progression-Free Survival (PFS)(Up to 1.5 years)
- Overall Survival (OS)(Up to 1.5 years)
- Daratumumab Serum Concentration(Cycle 1 Day 1 (C1D1):predose and postdose; C2D1 and C3D1:predose; C3D15: predose and postdose; C4D1: predose and postdose; C8D1: predose and postdose; C12D1: predose; end of treatment (37 days after last dose); and post last dose (up to 1.5 years))
- Number of Participants With Anti-Daratumumab Antibodies(Up to 1.5 years)
- Clinical Benefit Rate(Up to 1.5 years)
- Atezolizumab Serum Concentration(C1D1:predose and postdose; C1D2:predose and postdose; C2D1, C3D1:predose; C3D15:predose and postdose; C4D1:predose and postdose; C8D1:predose and postdose; C12D1:predose; end of treatment (37 days after last dose); and post last dose (up to 1.5 years))
- Number of Participants With Anti-Atezolizumab Antibodies(Up to 1.5 years)