Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors
Purpose
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RMC-5127 as a monotherapy and in combination with either daraxonrasib or cetuximab in adults with KRAS G12V-mutant solid tumors.
Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Colorectal Cancer (CRC)
- Pancreatic Adenocarcinoma
- Pancreatic Ductal Adenocarcinoma (PDAC)
- PDAC
- CRC
- NSCLC
- Pancreatic Cancer
- Lung Cancer (NSCLC)
- Advanced Solid Tumors
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts 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. - Pathologically documented, locally advanced or metastatic KRAS G12V-mutated solid tumor malignancy. - Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage. - Measurable per RECIST v1.1 - Adequate organ function (bone marrow, liver, kidney, coagulation). - Able to take oral medications.
Exclusion Criteria
- Primary central nervous system (CNS) tumors - Prior therapy with KRAS G12V inhibitor or direct RAS-targeted therapy (eg. degraders and/or inhibitors). - Any conditions that may affect the ability to take or absorb study drug. - Major surgery within 28 days prior to receiving study drug(s). - Patient is unable or unwilling to comply with protocol-required study visits or procedures.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm A: RMC-5127 Monotherapy |
Dose Escalation and Dose Expansion |
|
|
Experimental Arm B: RMC-5127 + Daraxonrasib Combination |
Dose Escalation and Dose Expansion |
|
|
Experimental Arm C: RMC-5127 + Cetuximab Combination |
Dose Escalation and Dose Expansion |
|
Recruiting Locations
New Haven, Connecticut 06511
Boston, Massachusetts 02215
New York, New York 10016
Dallas, Texas 75039
San Antonio, Texas 78229
More Details
- Status
- Recruiting
- Sponsor
- Revolution Medicines, Inc.
Detailed Description
This is an open-label, multicenter, Phase 1/1b study of RMC-5127 in adults with advanced KRAS G12V-mutant solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of three arms: RMC-5127 monotherapy arm, RMC-5127 plus daraxonrasib combination arm, and RMC-5127 plus cetuximab combination arm. All arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion. Both parts of the monotherapy arm may include Food Effect Cohorts.