Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mutated Pancreatic Adenocarcinoma (RASolute 309)
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
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.
研究概览
地位
详细说明
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).
研究类型
注册 (估计的)
阶段
- 第三阶段
联系人和位置
学习联系方式
- 姓名：Revolution Medicines Study Director
- 电话号码：1-844-2-REVMED
- 邮箱：medinfo@revmed.com
学习地点
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Arizona
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Phoenix、Arizona、美国、85054
- 招聘中
- Mayo Clinic Arizona
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接触：
- Tanios S. Bekaii-Saab
- 电话号码：855-776-0015
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Scottsdale、Arizona、美国、85258
- 招聘中
- HonorHealth Research Institute
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接触：
- Amy Malensek
- 电话号码：480-323-1350
- 邮箱：amalensek@honorhealth.com
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Florida
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Jacksonville、Florida、美国、32224
- 招聘中
- Mayo Clinic Florida
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接触：
- Hani M. Babiker
- 电话号码：855-776-0015
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Tampa、Florida、美国、33612
- 招聘中
- Moffitt Cancer Center
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接触：
- Cheyenne Schneider
- 电话号码：813-745-5166
- 邮箱：Cheyenne.Schneider@moffitt.org
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Minnesota
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Rochester、Minnesota、美国、55905
- 招聘中
- Mayo Clinic Rochester
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接触：
- Ben George
- 电话号码：855-776-0015
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Rhode Island
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Providence、Rhode Island、美国、02903
- 招聘中
- Rhode Island Hospital
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接触：
- Andrew Schumacher
- 电话号码：401-444-3234
- 邮箱：aschumacher@brownhealth.org
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- At least 18 years old and has provided informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- 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 v1.1.
- Adequate organ function (bone marrow, liver, kidney, coagulation).
Exclusion Criteria:
- 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.
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Arm A: daraxonrasib + zoldonrasib
combination of study drugs |
oral tablets oral tablets |
|
实验性的：Arm B: gemcitabine and nab-paclitaxel
chemotherapy |
IV infusion intravenous (IV) infusion |
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Overall survival (OS)
大体时间：Up to approximately 4 years
|
OS is defined as the time from randomization until death from any cause. |
Up to approximately 4 years
|
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Progression free survival (PFS)
大体时间：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. |
Up to approximately 4 years
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Incidence of adverse events (AEs)
大体时间：Up to approximately 4 years
|
Percentage of patients with AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5 |
Up to approximately 4 years
|
|
Changes in clinical laboratory test values
大体时间：Up to approximately 4 years
|
Number of patients with changes from baseline in clinical laboratory test values |
Up to approximately 4 years
|
|
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
大体时间：Up to approximately 4 years
|
EORTC QLQ-PAN26 consists of 26 questions relating to disease symptoms, treatment side effects and emotional issues specific to pancreatic cancer. The pancreatic pain subscale assesses abdominal pain, back pain, and pain while lying down. Change in score from baseline in the pain subscale will be assessed with higher scores on the pain subscale indicating more severe pain and worsening function. |
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
大体时间：Up to approximately 4 years
|
EORTC QLQ-C30 consists of 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, pain, nausea/vomiting, dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties), and an overall scale for global health status. It uses a mix of 4-point scales and 7-point scales. Change from baseline in EORTC QLQ-C30 global health status will be assessed. Higher scores on functional scales reflect better functioning, whereas higher scores on symptom scales reflect higher symptom burden. |
Up to approximately 4 years
|
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PFS by blinded independent central review (BICR)
大体时间：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 assessed per RECIST v1.1 by BICR |
Up to approximately 4 years
|
|
Objective response rate (ORR)
大体时间：Up to approximately 4 years
|
Objective response is defined as partial response (PR) or complete response (CR) per RECIST v1.1, as assessed by the Investigator. |
Up to approximately 4 years
|
|
Duration of response (DOR)
大体时间：Up to approximately 4 years
|
DOR is defined as time from first evidence of objective response (PR or CR) to disease progression or death due to any cause, whichever occurs first, as assessed by the investigator. |
Up to approximately 4 years
|
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Changes in vital signs
大体时间：Up to approximately 4 years
|
Number of patients with changes from baseline in vital signs |
Up to approximately 4 years
|
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Concentration of daraxonrasib and zoldonrasib in Arm A
大体时间：Up to Cycle 5 Day 1 (each cycle is 28 days)
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Pre-dose trough and post-dose blood concentrations of daraxonrasib and zoldonrasib at selected visits. |
Up to Cycle 5 Day 1 (each cycle is 28 days)
|
合作者和调查者
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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