A Phase 3, Randomized, Open-label, Multicenter Clinical Study to Evaluate the Safety and Efficacy of MK-1084 in Combination With Subcutaneous Pembrolizumab and Berahyaluronidase Alfa (MK-3475A) Versus MK-3475A in Combination With Pemetrexed/Platinum (Carboplatin or Cisplatin) Chemotherapy as First-line Treatment of Participants With KRAS G12C-Mutant, Advanced or Metastatic Nonsquamous NSCLC (KANDLELIT-007)
概览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 675
- 试验地点
- 180
- 主要终点
- Progression Free Survival (PFS) in Participants with Programmed Death-Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥1%
概览
简要总结
Researchers want to learn if the study medicines calderasib and subcutaneous (SC) pembrolizumab can be used to treat non-small cell lung cancer (NSCLC) when given together. Calderasib is a targeted therapy for the KRAS G12C mutation.
The goal of this study is to learn if people who receive calderasib with SC pembrolizumab live longer without the cancer growing or spreading than in people who receive SC pembrolizumab with chemotherapy.
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
- Single (Outcomes Assessor)
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
- •The main inclusion criteria include but are not limited to the following:
- •Has nonsquamous NSCLC (Stage IIIB, Stage IIIC) not eligible for curative resection or chemoradiation or Stage IV: M1a, M1b, or M1c
- •If human immunodeficiency virus (HIV) positive, must have well controlled HIV on antiretroviral therapy (ART)
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
- •Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea)
- •Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
- •Has a gastrointestinal disorder affecting absorption
- •Is HIV positive and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Has received prior systemic anticancer therapy for their advanced or metastatic NSCLC
- •Has known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has active autoimmune disease that has required systemic treatment in the past 2 years
研究组 & 干预措施
Pembrolizumab (+) Berahyaluronidase alfa + Chemotherapy
Participants will receive pembrolizumab (+) berahyaluronidase alfa at a fixed dose subcutaneously on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) and pemetrexed via intravenous (IV) infusion at a dose of 500 mg/m^2 on days 1 and 22 of cycles 1 and 3 until discontinuation criterion is met PLUS investigator's choice of carboplatin via IV infusion at area under curve (AUC) 5 mg/mL/minute on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks) OR cisplatin via IV infusion at a dose of 75 mg/m^2 on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks).
干预措施: Pembrolizumab (+) Berahyaluronidase alfa (Biological)
Pembrolizumab (+) Berahyaluronidase alfa + Chemotherapy
Participants will receive pembrolizumab (+) berahyaluronidase alfa at a fixed dose subcutaneously on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) and pemetrexed via intravenous (IV) infusion at a dose of 500 mg/m^2 on days 1 and 22 of cycles 1 and 3 until discontinuation criterion is met PLUS investigator's choice of carboplatin via IV infusion at area under curve (AUC) 5 mg/mL/minute on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks) OR cisplatin via IV infusion at a dose of 75 mg/m^2 on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks).
干预措施: Pemetrexed (Drug)
Pembrolizumab (+) Berahyaluronidase alfa + Chemotherapy
Participants will receive pembrolizumab (+) berahyaluronidase alfa at a fixed dose subcutaneously on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) and pemetrexed via intravenous (IV) infusion at a dose of 500 mg/m^2 on days 1 and 22 of cycles 1 and 3 until discontinuation criterion is met PLUS investigator's choice of carboplatin via IV infusion at area under curve (AUC) 5 mg/mL/minute on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks) OR cisplatin via IV infusion at a dose of 75 mg/m^2 on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks).
干预措施: Carboplatin (Drug)
Pembrolizumab (+) Berahyaluronidase alfa + Chemotherapy
Participants will receive pembrolizumab (+) berahyaluronidase alfa at a fixed dose subcutaneously on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) and pemetrexed via intravenous (IV) infusion at a dose of 500 mg/m^2 on days 1 and 22 of cycles 1 and 3 until discontinuation criterion is met PLUS investigator's choice of carboplatin via IV infusion at area under curve (AUC) 5 mg/mL/minute on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks) OR cisplatin via IV infusion at a dose of 75 mg/m^2 on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks).
干预措施: Cisplatin (Drug)
Calderasib + Pembrolizumab (+) Berahyaluronidase alfa
Participants will receive pembrolizumab (+) berahyaluronidase alfa at a fixed dose subcutaneously on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) plus calderasib until discontinuation criterion is met.
干预措施: Calderasib (Drug)
Calderasib + Pembrolizumab (+) Berahyaluronidase alfa
Participants will receive pembrolizumab (+) berahyaluronidase alfa at a fixed dose subcutaneously on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) plus calderasib until discontinuation criterion is met.
干预措施: Pembrolizumab (+) Berahyaluronidase alfa (Biological)
结局指标
主要结局
Progression Free Survival (PFS) in Participants with Programmed Death-Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥1%
时间窗: Up to approximately 48 months
PFS is defined as the time from randomization until either documented disease progression per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. PFS as determined by blinded independent central review (BICR) will be presented.
次要结局
- Duration of Response (DOR)(Up to approximately 48 months)
- Number of Participants Who Experienced One or More Adverse Events (AEs)(Up to approximately 81 months)
- Number of Participants Who Discontinued Study Treatment Due to an AE(Up to approximately 81 months)
- Change from Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire (EORTC QLQ-LC13)(Baseline and up to approximately 81 months)
- Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13(Baseline and up to approximately 81 months)
- Change from Baseline in Global Health Status/Quality of Life (GHS/QoL) (Items 29, 30) on the European Organization for Research and Treatment of Cancer QoL Questionnaire-Core 30 (EORTC QLQ-C30)(Baseline and up to approximately 81 months)
- Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30(Baseline and up to approximately 81 months)
- PFS in All Participants(Up to approximately 48 months)
- Overall Survival (OS) in Participants with PD-L1 TPS ≥1%(Up to approximately 62 months)
- OS in Participants in All Participants(Up to approximately 62 months)
- Overall Response Rate (ORR) in All Participants(Up to approximately 48 months)
- ORR in Participants with PD-L1 TPS ≥1%(Up to approximately 48 months)
- Time to Deterioration (TTD) in GHS/QoL (Items 29, 30) on the EORTC QLQ-C30(Baseline and up to approximately 81 months)
- TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30(Baseline and up to approximately 81 months)
- TTD in Cough Score (Item 31) on the EORTC QLQ-LC13(Baseline and up to approximately 81 months)
- TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13(Baseline and up to approximately 81 months)