A Phase 2, Multicenter, Open-label Study of Sotorasib (AMG 510) in Subjects With Stage IV NSCLC Whose Tumors Harbor a KRAS G12C Mutation in Need of First-line Treatment (CodeBreaK 201)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 42
- 试验地点
- 131
- 主要终点
- Objective Response Rate (OR)
研究概览
简要总结
The main objective of this study is to evaluate the tumor objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in participants who receive sotorasib at either 960 mg daily or 240 mg daily whose tumors are programmed death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) < 1% and/or harbor a serine/threonine kinase 11 (STK11) co-mutation, in a subgroup of participants with PD-L1 < 1% and in a subgroup of participants with STK11 co-mutation.
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
- •Adult (= or > 18 years old) with NSCLC
- •Untreated Stage IV metastatic disease. Participants who received adjuvant or neoadjuvant anti-tumor therapy are eligible if the adjuvant/neoadjuvant therapy was completed greater than 12 months prior to the development of metastatic stage IV disease
- •Pathologically documented metastatic NSCLC with KRAS G12C mutation (local confirmation)
- •Programmed death-ligand 1 (PD-L1) TPS Score < 1% and/or serine/threonine kinase 11 (STK11) co-mutation (local confirmation)
- •Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
- •No active brain metastases
- •Measurable disease per investigator interpretation using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
排除标准
- •Mixed small-cell lung cancer and NSCLC histology
- •Myocardial Infarction within 6 months of study Day 1
- •Use of proton-pump inhibitors (PPIs), histamine (H2) receptor antagonists (H2RA), strong inducers of cytochrome P450 (CYP) 3A4 (CYP3A4) or known CYP3A4 sensitive substrates or P-gp substrates
- •Therapeutic or palliative radiation therapy within 2 weeks of study day 1
- •Unable to take oral medication
- •Unable to receive both iodinated contrast for computed tomography (CT) scans and gadolinium contrast for magnetic resonance imagine (MRI) scans
研究组 & 干预措施
Sotorasib: 240 mg Daily
Participants with metastatic non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) p.G12C mutation whose tumors express < 1% programmed death-ligand 1 (PD-L1) and/or serine/threonine kinase 11 (STK11) mutation in need of first line treatment will be administered sotorasib 240 mg daily. Participants will be stratified by known presence of STK11 mutation.
干预措施: Sotorasib (Drug)
Sotorasib: 960 mg Daily
Participants with metastatic non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) p.G12C mutation whose tumors express < 1% programmed death-ligand 1 (PD-L1) and/or serine/threonine kinase 11 (STK11) mutation in need of first line treatment will be administered sotorasib 960 mg daily. Participants will be stratified by known presence of STK11 mutation.
干预措施: Sotorasib (Drug)
结局指标
主要结局
Objective Response Rate (OR)
时间窗: Up to 6 years
OR is defined as the total of Complete Response (CR) and Partial Response (PR).
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)
时间窗: From the first dose of trial drug until min (last dose + 30 days, end of trial [EOT]); median [min, max] duration was 5.32 [0.8, 30.9] months
Objective response was defined as best overall response (BOR) of complete response (CR) or partial response (PR), as defined by RECIST 1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Responses were assessed based on BICR.
次要结局
- Duration of Reponse (DOR)(Up to 6 years)
- Number of Participants with a Treatment-related Adverse Event(Day 1 up to Month 13)
- Time to Response (TTR)(Up to 6 years)
- Number of Participants with a Treatment-emergent Adverse Event (TEAE)(Day 1 up to Month 13)
- Disease Control Rate(Up to 6 years)
- Number of Participants with a Clinically Significant Change from Baseline in Vital Signs(Baseline (Screening; up to 28 days pre-dose) up to Month 13)
- Number of Participants with a Clinically Significant Change from Baseline in Electrocardiograms (ECGs)(Baseline (Screening; up to 28 days pre-dose) up to Month 13)
- Number of Participants with a Clinically Significant Change from Baseline in Clinical Laboratory Tests(Baseline (Screening; up to 28 days pre-dose) up to Month 13)
- Maximum Plasma Concentration (Cmax) of Sotorasib(Day 1 up to Month 3)
- Time to Reach Maximum Plasma Concentration (tmax) of Sotorasib(Day 1 up to Month 3)
- Area Under the Plasma Concentration-time Curve (AUC) of Sotorasib(Day 1 up to Month 3)
- Progression-free Survival (PFS)(Up to 6 years)
- Overall Survival (OS)(Up to 6 years)
- Disease Control Rate (DCR) Per RECIST Version 1.1 as Assessed by BICR(From randomization until EOT; median [min, max] time on trial was 9.72 [0.8, 38.0] months)
- Duration of Response (DOR) Per RECIST Version 1.1 as Assessed by BICR(From randomization until EOT; median [min, max] time on trial was 9.72 [0.8, 38.0] months)
- Time to Response (TTR) Per RECIST Version 1.1 as Assessed by BICR(From randomization until EOT; median [min, max] time on trial was 9.72 [0.8, 38.0] months)
- Progression-free Survival (PFS) as Assessed by BICR(From randomization until EOT; median [min, max] time on trial was 9.72 [0.8, 38.0] months)
- Overall Survival (OS)(From randomization until EOT; median [min, max] time on trial was 9.72 [0.8, 38.0] months)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-related TEAEs(From the first dose of trial drug until min (last dose + 30 days, EOT); median [min, max] duration was 5.32 [0.8, 30.9] months)
- Plasma Concentration of Sotorasib(Cycles 1 and 2: Day 1 pre-dose and 1 hour post-dose; Cycles 3, 4 and, 5: Day 1 pre-dose (cycle length = 21 days))