Pancreatic Cancer, Pancreatic Cancer Metastatic, PDAC, PDAC - Pancreatic Ductal Adenocarcinoma, Pancreatic Ductal Adenocarcinoma (PDAC), Pancreatic Adenocarcinoma Metastatic, Pancreatic Adenocarcinoma, Pancreatic Adenosquamous Carcinoma
Conditions
Keywords
Pancreatic Cancer, PDAC, Pancreatic Ductal Adenocarcinoma, RAS, KRAS, NRAS, HRAS, RAS Wild-Type, RAS Mutation, Pancreatic Cancer Metastatic, Pancreatic Adenocarcinoma Metastatic, Pancreatic Adenosquamous Carcinoma, Pancreatic Adenocarcinoma
Brief summary
The purpose of this study is to evaluate the safety and efficacy of an investigational RAS(ON) inhibitor administered as monotherapy or in combination with chemotherapy, compared with standard of care (SOC) chemotherapy alone.
Detailed description
This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with daraxonrasib monotherapy or daraxonrasib plus gemcitabine and nab-paclitaxel 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 pancreatic adenocarcinoma. Patients will be randomized to one of three arms: daraxonrasib (Arm A), daraxonrasib + gemcitabine and nab-paclitaxel (Arm B), or gemcitabine and nab-paclitaxel (Arm C).
Interventions
Sponsors
Revolution Medicines, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. * Diagnosis of metastatic disease ≤ 6 weeks prior to informed consent. * Documented RAS mutation status, either mutant or wild-type. * Measurable disease per RECIST v1.1. * Adequate organ function (bone marrow, liver, kidney, coagulation). * Able to take oral medications.
Exclusion criteria
* Prior treatment with systemic anticancer therapy in metastatic setting or prior RAS-targeted therapy in any treatment setting. * Active or known history of untreated central nervous system metastatic 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | Up to approximately 2 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) | Up to approximately 2 years | OS is defined as the time from randomization until death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to approximately 2 years | Objective response is defined as partial response (PR) or complete response (CR) per RECIST v1.1, as assessed by the Investigator. |
| Duration of response (DOR) | Up to approximately 2 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. |
| Concentration of daraxonrasib in Arm A and B | Up to Cycle 5 Day 1 (each cycle is 28 days) | Pre-dose trough and post-dose blood concentrations of daraxonrasib at selected visits. |
| Health-related outcome assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26) | Up to approximately 2 years | Change from baseline in EORTC QLQ-PAN26 pain scale |
| Quality of life as assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Up to approximately 2 years | Change from baseline in EORTC QLQ-C30 global health status |
| Incidence of adverse events (AEs) | Up to approximately 2 years | Percentage of patients with AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v6 |
| Changes in vital signs | Up to approximately 2 years | Number of patients with clinically significant changes in vital signs |
| Changes in clinical laboratory test values | Up to approximately 2 years | Number of patients with changes from baseline in clinical laboratory test values |
Countries
United States
Contacts
CONTACTRevolution Medicines Study Director
Outcome results
None listed