A Phase 2 Trial of Combination Therapies With Adagrasib in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 90
- 试验地点
- 260
- 主要终点
- Objective Response Rate (ORR) for Cohort A and E
研究概览
简要总结
Study CA239-0010 is an open-label, Phase 2 clinical trial evaluating the clinical efficacy of adagrasib in combination with pembrolizumab and chemotherapy in the first-line setting for patients with advanced NSCLC with TPS ≥ 1%, TPS <50% and KRAS G12C mutation
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Cohort A* (closed): Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (squamous or nonsquamous) KRASG12C mutation and histologically confirmed PD-L1 TPS ≥1%.
- •Cohort C: Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (non-squamous only) KRASG12C mutation and histologically confirmed PD-L1 TPS < 50% AND previously completed 4 cycles of standard-of-care platinum based induction chemotherapy with pembrolizumab AND experienced stable disease, partial response, or complete response per investigator's assessment after 4 cycles OR if patients received <4 cycles of a platinum-based induction, was stopped early due to intolerable toxicity
- •Cohort E: Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (non-squamous only) KRASG12C mutation and histologically confirmed PD-L1 TPS < 50%
- •Presence of measurable disease per RECIST v1.1
排除标准
- •All Cohorts: Any prior therapy targeting KRASG12C mutation in any setting
- •Cohorts A & E: Prior systemic therapy for locally advanced or metastatic NSCLC, including chemotherapy, immune checkpoint inhibitor therapy or chemoimmunotherapy (note: prior systemic therapy or chemoradiation given in the adjuvant or neoadjuvant setting are allowed if last dose of prior systemic treatment was >1 year prior to first dose of study treatment)
- •Cohort C: received maintenance therapy (e.g, pembrolizumab and/or pemetrexed following completion of 4-6 cycles of a platinum-based regimen administered in the first-line setting
- •Radiation to the lung > 30 Gy within 6 months prior to first dose of study treatment
- •Active brain metastases
研究组 & 干预措施
Cohort E
Adagrasib 400 mg BID + pembrolizumab 200 mg Q3W + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 Q3W OR carboplatin AUC 5 Q3W for 4 cycles, followed by adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W (up to 31 cycles)
干预措施: Cisplatin/Carboplatin (Combination Product)
Cohort A: PD-L1 TPS≥ 1% (Closed)
Adagrasib 400 mg BID for 2 cycles followed by adagrasib 400 mg BID + pembrolizumab 200 mg every 3 weeks (Q3W) up to 35 cycles
干预措施: Adagrasib oral dose of 400 mg twice daily tablets (Drug)
Cohort C
Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles
干预措施: Adagrasib oral dose of 400 mg twice daily tablets (Drug)
Cohort C
Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles
干预措施: Cisplatin/Carboplatin (Combination Product)
Cohort E
Adagrasib 400 mg BID + pembrolizumab 200 mg Q3W + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 Q3W OR carboplatin AUC 5 Q3W for 4 cycles, followed by adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W (up to 31 cycles)
干预措施: Adagrasib oral dose of 400 mg twice daily tablets (Drug)
Cohort E
Adagrasib 400 mg BID + pembrolizumab 200 mg Q3W + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 Q3W OR carboplatin AUC 5 Q3W for 4 cycles, followed by adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W (up to 31 cycles)
干预措施: Chemotherapy: Pemetrexed (Combination Product)
Cohort C
Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles
干预措施: Pembrolizumab (Combination Product)
Cohort C
Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles
干预措施: Chemotherapy: Pemetrexed (Combination Product)
Cohort E
Adagrasib 400 mg BID + pembrolizumab 200 mg Q3W + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 Q3W OR carboplatin AUC 5 Q3W for 4 cycles, followed by adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W (up to 31 cycles)
干预措施: Pembrolizumab (Combination Product)
结局指标
主要结局
Objective Response Rate (ORR) for Cohort A and E
时间窗: 30 months
Defined as the percent of patients documented to have a confirmed CR or PR
Progression-free Survival (PFS) at six months for Cohort C
时间窗: 30 months
PFS is defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
次要结局
- Duration of Response (DOR)(30 months)
- Overall Survival (OS)(30 months)
- Population pharmacokinetic (PK) Model Derived AUC at Steady State (AUCtau,ss).(Time Frame: Pre-dose and 4-6 hours post dose; up to 6 months)
- Adverse Events(30 months)
- Progression-free Survival (PFS)(30 months)
- Cohorts C and E: DLTs during SLI (Safety Lead In)(30 months)