Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors

NCT07349537 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: RMC-5127-001
• Study Type: interventional
• Target: 574
• Locations: 1 country
• Sites: 5

Brief Summary

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); PDAC; Colorectal Cancer (CRC); Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma (PDAC); CRC; NSCLC; Pancreatic Cancer; Lung Cancer (NSCLC); Advanced Solid Tumors

Keywords

Advanced Solid Tumors; Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma; PDAC; Colorectal Cancer; CRC; Lung Cancer; Non-small Cell Lung Cancer; NSCLC; RAS; KRAS; RAS Mutation

Outcome Measures

Primary Outcomes (5)

• Number of patients with adverse events (AEs)

  Number of patients with AEs as assessed by Common Terminology Criteria for Adverse Events CTCAE v5

  Up to approximately 3 years

• Changes in vital signs

  Number of patients with changes from baseline in vital signs

  Up to approximately 3 years

• Changes in electrocardiogram (ECG) test values

  Number of patients with changes from baseline in ECG test values

  Up to approximately 3 years

• Changes in clinical laboratory test values

  Number of patients with changes from baseline in clinical laboratory test values

  Up to approximately 3 years

• Dose Limiting Toxicities

  Number of patients with dose limiting toxicities

  Up to 28 days

Secondary Outcomes (7)

• Cmax concentrations of RMC-5127 and daraxonrasib

  Up to Cycle 5 Day 1 (each cycle is up to 28 days)

• Tmax concentration of RMC-5127 and daraxonrasib

  Up to Cycle 5 Day 1 (each cycle is up to 28 days)

• AUC concentrations of RMC-5127 and daraxonrasib

  Up to Cycle 5 Day 1 (each cycle is up to 28 days)

• Ratio of accumulation of RMC-5127

  Up to Cycle 5 Day 1 (each cycle is up to 28 days)

• Half-Life of RMC-5127 and daraxonrasib

  Up to Cycle 5 Day 1 (each cycle is up to 28 days)

Study Arms (3)

Arm A: RMC-5127 Monotherapy

EXPERIMENTAL

Dose Escalation and Dose Expansion

Drug: RMC-5127

Arm B: RMC-5127 + Daraxonrasib Combination

EXPERIMENTAL

Dose Escalation and Dose Expansion

Drug: RMC-5127; Drug: daraxonrasib

Arm C: RMC-5127 + Cetuximab Combination

EXPERIMENTAL

Dose Escalation and Dose Expansion

Drug: RMC-5127; Drug: cetuximab

Interventions

RMC-5127 DRUG

oral tablets

Arm A: RMC-5127 Monotherapy; Arm B: RMC-5127 + Daraxonrasib Combination; Arm C: RMC-5127 + Cetuximab Combination

daraxonrasib DRUG

oral tablets

Arm B: RMC-5127 + Daraxonrasib Combination

cetuximab DRUG

IV infusion

Arm C: RMC-5127 + Cetuximab Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Revolution Medicines, Inc.: lead

Study Sites (5)

START Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

NEXT - Dallas

Dallas, Texas, 75039, United States

RECRUITING

NEXT

San Antonio, Texas, 78229, United States

RECRUITING

START - San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

NEXT - Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Pancreatic Neoplasms; Lung Neoplasms

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Revolution Medicines Study Director

CONTACT

1-844-2-REVMED; medinfo@revmed.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2026
• First Posted: January 16, 2026
• Study Start: January 8, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: February 4, 2026

Record last verified: 2026-02

Locations

US (5)