A Phase 3, Randomized, Open-Label Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Patients With Metastatic KRAS G12D-Mutated Pancreatic Adenocarcinoma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- Progression free survival (PFS)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of combination therapy with two investigational RAS(ON) inhibitors (daraxonrasib and zoldonrasib) compared to chemotherapy.
详细描述
This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with daraxonrasib plus zoldonrasib will improve progression-free survival and/or overall survival compared with standard gemcitabine and nab-paclitaxel when given as first-line treatment in patients with metastatic KRAS G12D-mutated pancreatic adenocarcinoma.
Patients will be randomized to one of two arms: daraxonrasib + zoldonrasib (Arm A) or gemcitabine and nab-paclitaxel (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 pancreatic adenocarcinoma, including adenosquamous carcinoma, not previously treated in the locally advanced unresectable or metastatic setting.
- •No prior treatment in the locally advanced unresectable or metastatic setting
- •Diagnosis of metastatic disease ≤ 6 weeks prior to informed consent.
- •Documented KRAS G12D mutation status.
- •Measurable disease per RECIST v1.
- •Adequate organ function (bone marrow, liver, kidney, coagulation).
排除标准
- •Mutation status with known driver mutations for which there are approved targeted therapies.
- •Acinar cell carcinoma, pancreatic neuroendocrine tumors, tumors involving islet cells or islet cell neoplasms, and other non-adenocarcinoma pancreatic malignancies.
- •Tumors determined to originate from non-pancreatic primary sites.
- •Prior treatment with MAPK-pathway targeted therapy or administration of RAS-targeted vaccine in the metastatic setting.
- •Active or known history of untreated central nervous system metastatic or leptomeningeal disease.
- •Any conditions that may affect the ability to take or absorb study drug.
- •Major surgery within 28 days prior to randomization.
- •Patient is unable or unwilling to comply with protocol-required study visits or procedures.
- •Additional inclusion & exclusion criteria may apply.
研究组 & 干预措施
Arm A: daraxonrasib + zoldonrasib
combination of study drugs
干预措施: daraxonrasib (Drug)
Arm B: gemcitabine and nab-paclitaxel
chemotherapy
干预措施: nab-paclitaxel (Drug)
Arm A: daraxonrasib + zoldonrasib
combination of study drugs
干预措施: zoldonrasib (Drug)
Arm B: gemcitabine and nab-paclitaxel
chemotherapy
干预措施: gemcitabine (Drug)
结局指标
主要结局
Progression free survival (PFS)
时间窗: Up to approximately 4 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 Investigator.
Overall survival (OS)
时间窗: Up to approximately 4 years
OS is defined as the time from randomization until death from any cause.
次要结局
- Incidence of adverse events (AEs)(Up to approximately 4 years)
- Quality of life as assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) global health status score(Up to approximately 4 years)
- Changes in vital signs(Up to approximately 4 years)
- Changes in clinical laboratory test values(Up to approximately 4 years)
- PFS by blinded independent central review (BICR)(Up to approximately 4 years)
- Objective response rate (ORR)(Up to approximately 4 years)
- Duration of response (DOR)(Up to approximately 4 years)
- Concentration of daraxonrasib and zoldonrasib in Arm A(Up to Cycle 5 Day 1 (each cycle is 28 days))
- Health-related outcome assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26) pain scale(Up to approximately 4 years)