RASolute 302: A Phase 3 Multicenter, Open-label, Randomized Study of Daraxonrasib (RMC-6236) Versus Investigator's Choice of Standard of Care Therapy in Patients With Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 500
- 试验地点
- 118
- 主要终点
- Progression free survival (PFS) in the RAS G12-mutant population
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of a novel RAS(ON) inhibitor compared to standard(s) of care (SOC) treatment.
详细描述
This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with RMC-6236 will improve progression free survival (PFS) or overall survival (OS) compared to Investigator's choice of standard of care chemotherapy in patients with metastatic PDAC who were previously treated with one prior line of therapy with 5-fluorouracil (5-FU) based or gemcitabine-based regimen.
Patients will be randomized in a 1:1 ratio to receive RMC-6236 (Arm A) or Investigator's choice of standard of care chemotherapy (Arm B).
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
- •At least 18 years old and has provided informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Histologically or cytologically confirmed PDAC with metastatic disease.
- •Measurable disease per RECIST 1.
- •Adequate organ function (bone marrow, liver, kidney, coagulation)
- •Documented RAS mutation status, either mutant or wild-type. RAS mutations defined as nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61).
- •Able to take oral medications.
排除标准
- •Prior therapy with direct RAS-targeted therapy (eg. degraders and/or inhibitors).
- •History of or known central nervous system metastatic disease.
- •Any conditions that may affect the ability to take or absorb study treatment
- •Major surgery within 4 weeks prior to randomization.
- •Patient is unable or unwilling to comply with protocol-required study visits or procedures
研究组 & 干预措施
RMC-6236
Study drug
干预措施: RMC-6236 (Drug)
Investigator's choice of standard of care therapy
Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments:
- Gemcitabine and nab-paclitaxel (GnP)
- Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX)
- Liposomal irinotecan (Nal-IRI + 5-FU/LV)
- Oxaliplatin, leucovorin and 5-FU IV (FOLFOX)
干预措施: Gemcitabine (Drug)
Investigator's choice of standard of care therapy
Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments:
- Gemcitabine and nab-paclitaxel (GnP)
- Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX)
- Liposomal irinotecan (Nal-IRI + 5-FU/LV)
- Oxaliplatin, leucovorin and 5-FU IV (FOLFOX)
干预措施: nab-paclitaxel (Drug)
Investigator's choice of standard of care therapy
Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments:
- Gemcitabine and nab-paclitaxel (GnP)
- Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX)
- Liposomal irinotecan (Nal-IRI + 5-FU/LV)
- Oxaliplatin, leucovorin and 5-FU IV (FOLFOX)
干预措施: Liposomal irinotecan (Drug)
Investigator's choice of standard of care therapy
Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments:
- Gemcitabine and nab-paclitaxel (GnP)
- Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX)
- Liposomal irinotecan (Nal-IRI + 5-FU/LV)
- Oxaliplatin, leucovorin and 5-FU IV (FOLFOX)
干预措施: Irinotecan (Drug)
Investigator's choice of standard of care therapy
Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments:
- Gemcitabine and nab-paclitaxel (GnP)
- Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX)
- Liposomal irinotecan (Nal-IRI + 5-FU/LV)
- Oxaliplatin, leucovorin and 5-FU IV (FOLFOX)
干预措施: 5-fluorouracil (Drug)
Investigator's choice of standard of care therapy
Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments:
- Gemcitabine and nab-paclitaxel (GnP)
- Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX)
- Liposomal irinotecan (Nal-IRI + 5-FU/LV)
- Oxaliplatin, leucovorin and 5-FU IV (FOLFOX)
干预措施: Oxaliplatin (Drug)
Investigator's choice of standard of care therapy
Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments:
- Gemcitabine and nab-paclitaxel (GnP)
- Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX)
- Liposomal irinotecan (Nal-IRI + 5-FU/LV)
- Oxaliplatin, leucovorin and 5-FU IV (FOLFOX)
干预措施: leucovorin (Drug)
结局指标
主要结局
Progression free survival (PFS) in the RAS G12-mutant population
时间窗: Up to approximately 3 years
PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is per response evaluation criteria in solid tumors (RECIST) v1.1 and as assessed by blinded independent central review (BICR)
Overall survival (OS) in the RAS G12-mutant population
时间窗: Up to approximately 3 years
OS is defined as the time from randomization until death from any cause.
次要结局
- PFS in the all-patient population(Up to approximately 3 years)
- Objective response in the RAS G12 and all-patient populations(Up to approximately 3 years)
- OS in the all-patient population(Up to approximately 3 years)
- Time to deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26) in the RAS G12 and all-patient populations(Up to approximately 3 years)
- Time to deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in the RAS G12 and all-patient populations(Up to approximately 3 years)
- Objective response per investigator in RAS G12 and all- patient populations(Up to approximately 3 years)
- Duration of response (DOR) in RAS G12 and all-patient populations(Up to approximately 3 years)
- Time to response (TTR) in RAS G12 and all-patient populations(Up to approximately 3 years)
- Percentage of patients with adverse events (AEs)(Up to approximately 3 years)
- Pharmacokinetics of RMC-6236 in RAS G12 and all-patient populations(Up to approximately 3 years)