A Randomized, Controlled, Open Label, Phase III Study Evaluating the Efficacy and Safety of JDQ443 Versus Docetaxel in Previously Treated Subjects With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 95
- 试验地点
- 55
- 主要终点
- Progression free survival (PFS)
研究概览
简要总结
This is a phase III randomized open label study designed to compare JDQ443 as monotherapy to docetaxel in participants with advanced non-small cell lung cancer (NSCLC) harboring a KRAS G12C mutation who have been previously treated with a platinum-based chemotherapy and immune checkpoint inhibitor therapy either in sequence or in combination.
详细描述
The study has been designed as a Phase III trial and consists of 2 parts:
- Randomized part will evaluate the efficacy and safety of JDQ443 as monotherapy in comparison with docetaxel. Participants randomized to docetaxel arm will have the opportunity to cross-over to JDQ443 at disease progression per RECIST 1.1 confirmed by BIRC.
- Extension part will be open after final progression-free survival (PFS) analysis (if the primary endpoint has met statistical significance) to allow participants randomized to docetaxel treatment to crossover to receive JDQ443 treatment regardless of progression on docetaxel.
The study population will include adult participants with locally advanced or metastatic (stage IIIB/IIIC or IV) KRAS G12C mutant non-small cell lung cancer (by tissue or plasma as determined by a Novartis-designated central laboratory or accepted local tests) who have received prior platinum-based chemotherapy and prior immune checkpoint inhibitor therapy administered either in sequence or as combination therapy.
Approximately 360 participants will be randomized to JDQ443 or docetaxel in a 1:1 ratio stratified by prior line of therapy and ECOG performance status.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant has histologically confirmed locally advanced/metastatic (stage IIIB/IIIC or IV)
- •Participant has a KRAS G12C mutation present in tumor tissue or plasma prior to enrollment, as determined by a Novartis designated central laboratory or by accepted local tests.
- •Participants has received one prior platinum-based chemotherapy regimen and one prior immune checkpoint inhibitor therapy for locally advanced or metastatic disease
- •Participant has at least 1 evaluable (measurable or non-measurable) lesion by RECIST 1.1 at the screening visit.
排除标准
- •Participants who have previously received docetaxel (except if received in neoadjuvant or adjuvant setting with no progression within 12 months after the of end of treatment), or any other KRAS G12C inhibitor.
- •Participant has EGFR-sensitizing mutation and/or ALK rearrangement by local laboratory testing. Participants with other druggable alterations will be excluded if required by local guidelines.
- •Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Participant has an history of interstitial lung disease or pneumonitis grade >
- •Other inclusion/exclusion criteria may apply
研究组 & 干预措施
Docetaxel
Participant will be treated with docetaxel following local guidelines as per standard of care and product labels
干预措施: docetaxel (Drug)
JDQ443
Participants will be treated with JDQ443
干预措施: JDQ443 (Drug)
结局指标
主要结局
Progression free survival (PFS)
时间窗: Approximately up to 24 months
PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is based on central assessment and using RECIST 1.1 criteria.
次要结局
- Duration of Response (DOR)(Approximately up to 33 months)
- Progression-Free Survival after next line therapy (PFS2)(Approximately up to 33 months)
- Change from baseline in EORTC-EQ-5D-5L(Approximately up to 33 months)
- Time To Response (TTR)(Approximately up to 33 months)
- Time to definitive 10-point deterioration symptom scores of chest pain, cough and dyspnea per QLQ-LC13(Approximately up to 33 months)
- Change from baseline in NSCLC-SAQ(Approximately up to 33 months)
- Overall Survival (OS)(Approximately up to 33 months)
- Overall Response Rate (ORR)(Approximately up to 33 months)
- Concentration of JDQ443 and its metabolite in plasma(Approximately up to 33 months)
- Time to definitive deterioration of Eastern Cooperative Group of Oncology Group (ECOG) performance status(Approximately up to 33 months)
- Time to definitive 10-point deterioration in global health status/QoL, shortness of breath and pain per QLQ-C30(Approximately up to 33 months)
- Change from baseline in EORTC-QLQ-C30(Approximately up to 33 months)
- Change from baseline in EORTC-QLQ-LC13(Approximately up to 33 months)
- Disease Control Rate (DCR)(Approximately up to 33 months)