NCT04685135进行中（未招募）3 期
A Randomized Phase 3 Study of MRTX849 Versus Docetaxel in Patients With Previously Treated Non-Small Cell Lung Cancer With KRAS G12C Mutation
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 453
- 试验地点
- 380
- 主要终点
- Progression-Free Survival (PFS) as Per Blinded Independent Central Review
研究概览
简要总结
This Phase 3 study will evaluate the efficacy of the investigational agent MRTX849 (adagrasib) versus docetaxel in patients who have been previously treated for metastatic NSCLC with a KRAS G12C 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
- •Histologically or cytologically confirmed diagnosis of NSCLC with KRAS G12C mutation.
- •Candidacy to receive treatment with docetaxel.
- •Crossover Inclusion Criteria:
- •Evidence of RECIST 1.1 defined disease progression on docetaxel per BICR
- •ECOG performance status 0-2
排除标准
- •Prior treatment with an agent targeting KRAS G12C (e.g., AMG 510, Sotorasib).
- •Active brain metastases.
- •Crossover Exclusion Criteria:
- •Receipt of any other systemic anti-cancer therapy after last administration of docetaxel on the study.
研究组 & 干预措施
MRTX849
Experimental
干预措施: MRTX849 (Drug)
Docetaxel
Active Comparator
干预措施: Docetaxel (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) as Per Blinded Independent Central Review
时间窗: From randomization to the date of progression or death due to any cause, whichever occurs first (up to approximately 143 weeks)
Progression-free survival (PFS) is defined as the time from randomization to the date of progression or death due to any cause, whichever occurs first. 95% CI was obtained using Brookmeyer and Crowley method. Participants who are not observed to have progressed or died are censored at the date of last evaluable tumor assessment. Disease progression assessed as per RECISIST 1.1 was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
次要结局
- Overall Survival (OS)(From randomization till death due to any cause (up to approximately 143 weeks))
- Objective Response Rate (ORR) as Per Blinded Independent Central Review(From randomization till death or till disease progression or initiation of follow-up anti-cancer therapy or withdrawal of consent prior to minimum efficacy follow-up (up to 143 weeks))
- Duration of Response (DOR) as Per Blinded Independent Central Review(First documentation of objective response (CR or PR) to the first documentation of PD or to death due to any cause (Up to approximately 22 months))
- 1-Year Survival Rate(Up to 49 months)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From first dose of treatment (Day 1) till 28 days after last dose (Up to approximately 110 weeks))
- Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters(From first dose of treatment (Day 1) till 28 days after last dose (Up to approximately 110 weeks))
- Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters(From first dose of treatment (Day 1) till 28 days after last dose (Up to approximately 110 weeks))
- Plasma Concentration of Adagrasib(Day 1 of Cycle 1 (Pre-Dose and Peak), Cycle 2 (Pre-Dose and Peak), Cycle 3 (Pre-Dose), Cycle 5 (Pre-Dose), Cycle 7 (Pre-Dose) (Each cycle is of 21 days))
- Change From Baseline in Lung Cancer Symptom Scale (LCSS) Average Total Score(Baseline (Day 1) and up to End of Treatment (Up to approximately 106 weeks))
- Change From Baseline in Lung Cancer Symptom Scale (LCSS) Average Symptom Burden Index Score(Baseline (Day 1) and up to End of Treatment (Up to approximately 106 weeks))
- Change From Baseline in Lung Cancer Symptom Scale (LCSS) 3-Item Global Index Score(Baseline (Day 1) and up to End of Treatment (Up to approximately 106 weeks))
- Change From Baseline at End of Treatment in European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) Visual Analogue Scale Score(Baseline (Day 1) and up to End of Treatment (Up to approximately 106 weeks))
- Change From Baseline at End of Treatment in European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) Health Utility Index Score(Baseline (Day 1) and up to End of Treatment (Up to approximately 106 weeks))
研究者
研究点 (380)
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相关资讯
Targeted Therapies Improve Outcomes in NSCLC Based on Molecular Profiling• Comprehensive molecular testing, including NGS, is vital for identifying driver mutations in NSCLC, enabling precise targeted therapy and improved overall survival.
• MET alterations, such as exon 14 skipping mutations, are effectively targeted by TKIs like crizotinib, capmatinib, and tepotinib, demonstrating significant response rates.
• RET fusions, present in 1-2% of NSCLC cases, are successfully targeted by selpercatinib and pralsetinib, showing improved PFS and ORR compared to chemotherapy.
• KRAS G12C mutations are now actionable with sotorasib and adagrasib, which have shown superior ORR and PFS compared to docetaxel in previously treated patients.last yearAdagrasib Demonstrates Superior Efficacy Over Docetaxel in KRAS G12C-Mutated NSCLC- Adagrasib significantly improves progression-free survival (PFS) compared to docetaxel in KRAS G12C-mutated non-small cell lung cancer (NSCLC) patients previously treated with chemotherapy and immunotherapy.
- The KRYSTAL-12 trial showed a statistically significant increase in objective response rate (ORR) with adagrasib versus docetaxel, indicating enhanced tumor response.
- Adagrasib demonstrates promising intracranial activity, with a higher intracranial ORR compared to docetaxel, offering potential benefits for patients with CNS metastases.
- Ongoing trials are exploring adagrasib's potential as a first-line therapy in combination with immunotherapy for KRAS G12C-mutated NSCLC.last year