A Randomized, Open-Label, Phase 3 Study to Evaluate Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy for the First-Line Treatment of Patients With Metastatic Non-Small Cell Lung Cancer With No Epidermal Growth Factor Receptor or Anaplastic Lymphoma Kinase Genomic Tumor Aberrations
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,021
- 试验地点
- 354
- 主要终点
- Overall Survival (OS) in Participants With Positive Programmed Cell Death-Ligand 1 (PD-L1) Expression (≥1%Tumor Cells) and in all Randomized Participants.
研究概览
简要总结
The primary objective of this study is to compare the effect of zimberelimab (ZIM) and domvanalimab (DOM) in combination with chemotherapy relative to pembrolizumab (PEMBRO) in combination with chemotherapy on overall survival (OS) in patients with untreated metastatic non-small cell lung cancer with no actionable genomic alteration.
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
- •Life expectancy ≥ 3 months.
- •Pathologically documented NSCLC that meets both of the criteria below:
- •Have documented evidence of Stage IV NSCLC disease at the time of enrollment (based on American Joint Committee on Cancer (AJCC), Eighth Edition).
- •Have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations.
- •Have no actionable genomic alterations such as ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), RET mutations, or other driver oncogenes with approved frontline therapies.
- •Have not received prior systemic treatment for metastatic NSCLC.
- •Measurable disease per RECIST v1.1 criteria by investigator assessment.
- •Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or
- •Have adequate organ functions.
排除标准
- •Have mixed small-cell lung cancer (SCLC) and NSCLC histology.
- •Positive serum pregnancy test or individuals who are breastfeeding or have plans to breastfeed during the study period.
- •Received prior treatment with any anti-PD-1, anti-PD-L1, or any other antibody targeting an immune checkpoint.
- •Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
- •Have an active second malignancy or have had an active second malignancy within 3 years prior to enrollment.
- •Have an active autoimmune disease that required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
- •Are receiving chronic systemic steroids.
- •Have significant third-space fluid retention.
- •Have untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal perforation within 6 months of enrollment.
- •Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- •Has had an allogenic tissue/solid organ transplant.
- •Have received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.
- •Have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy
Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Zimberelimab (Drug)
Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy
Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Domvanalimab (Drug)
Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy
Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Carboplatin (Drug)
Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy
Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Cisplatin (Drug)
Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy
Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Paclitaxel (Drug)
Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy
Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Nab-paclitaxel (Drug)
Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy
Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Pemetrexed (Drug)
Pembrolizumab (PEMBRO) + Chemotherapy
Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Pembrolizumab (Drug)
Pembrolizumab (PEMBRO) + Chemotherapy
Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Carboplatin (Drug)
Pembrolizumab (PEMBRO) + Chemotherapy
Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Cisplatin (Drug)
Pembrolizumab (PEMBRO) + Chemotherapy
Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Paclitaxel (Drug)
Pembrolizumab (PEMBRO) + Chemotherapy
Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Nab-paclitaxel (Drug)
Pembrolizumab (PEMBRO) + Chemotherapy
Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Pemetrexed (Drug)
Zimberelimab (ZIM) + Chemotherapy
Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Zimberelimab (Drug)
Zimberelimab (ZIM) + Chemotherapy
Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Carboplatin (Drug)
Zimberelimab (ZIM) + Chemotherapy
Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Cisplatin (Drug)
Zimberelimab (ZIM) + Chemotherapy
Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Paclitaxel (Drug)
Zimberelimab (ZIM) + Chemotherapy
Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Nab-paclitaxel (Drug)
Zimberelimab (ZIM) + Chemotherapy
Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
- Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
- Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
干预措施: Pemetrexed (Drug)
结局指标
主要结局
Overall Survival (OS) in Participants With Positive Programmed Cell Death-Ligand 1 (PD-L1) Expression (≥1%Tumor Cells) and in all Randomized Participants.
时间窗: Up to 68 months
OS is defined as the time from the date of randomization to the date of death from any cause.
次要结局
- Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1(Upt to 50 months)
- Objective Response Rate (ORR) as Assessed by BICR per RECIST Version 1.1(Up to 50 Months)
- Duration of Response (DOR) as Assessed by BICR per RECIST Version 1.1(Up to 50 Months)
- Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)(First dose date up to 50 months plus 30 days)
- Percentage of Participants Experiencing Clinical Laboratory Abnormalities(First dose date up to 50 months plus 30 days)
- Time to First Symptom Deterioration in Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Total Score(Baseline, Up to 50 Months)