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NCT Number: NCT07349537

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

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.

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Key information

Conditions

Non-small Cell Lung Cancer (NSCLC) Advanced Solid Tumors Bronchial Neoplasms CRC Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Colonic Diseases Colorectal Cancer (CRC) Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Lung Cancer (NSCLC) Lung Diseases Lung Neoplasms NSCLC Neoplasms Neoplasms by Site PDAC Pancreatic Adenocarcinoma Pancreatic Cancer Pancreatic Diseases Pancreatic Ductal Adenocarcinoma (PDAC) Pancreatic Neoplasms Rectal Diseases Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Yale Cancer Center, New Haven, Connecticut, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

RMC-5127

Drug

oral tablets

daraxonrasib

Drug

oral tablets

Cetuximab

Drug

IV infusion

Primary outcomes

  1. Number of patients with adverse events (AEs)

    Time frame: Up to approximately 3 years

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

  2. Changes in vital signs

    Time frame: Up to approximately 3 years

    Number of patients with changes from baseline in vital signs

  3. Changes in electrocardiogram (ECG) test values

    Time frame: Up to approximately 3 years

    Number of patients with changes from baseline in ECG test values

  4. Changes in clinical laboratory test values

    Time frame: Up to approximately 3 years

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

  5. Dose Limiting Toxicities

    Time frame: Up to 28 days

    Number of patients with dose limiting toxicities

Secondary outcomes

  1. Cmax concentrations of RMC-5127 and daraxonrasib

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

    Maximum blood concentration (Cmax) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and Cmax of daraxonrasib in combination with RMC-5127 over time as applicable

  2. Tmax concentration of RMC-5127 and daraxonrasib

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

    Time to reach maximum blood concentration (Tmax) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and Tmax of daraxonrasib in combination with RMC-5127 over time as applicable

  3. AUC concentrations of RMC-5127 and daraxonrasib

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

    Area under the blood concentration time curve (AUC) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and AUC of daraxonrasib in combination with RMC-5127 over time as applicable

  4. Ratio of accumulation of RMC-5127

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

    Ratio of accumulation of RMC-5127 from a single dose to steady state with repeated dosing as monotherapy and in combination with darabxrasib or cetuximab over time as applicable

  5. Half-Life of RMC-5127 and daraxonrasib

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

    Elimination Half-Life (t1/2) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and t1/2 of daraxonrasib in combination with RMC-5127 over time as applicable

  6. Objective Response Rate (ORR)

    Time frame: Up to approximately 3 years

    ORR per response evaluation criteria in solid tumors (RECIST) v1.1

  7. Duration of Response (DOR)

    Time frame: Up to approximately 3 years

    DOR per RECIST v1.1

Study contacts

Contact information is provided by the study sponsor or research team.

Revolution Medicines Study Director

CONTACT

[email protected]

1-844-2-REVMED

Sponsors and collaborators

Lead sponsor

Revolution Medicines, Inc.

Industry

Registry information

Official study title

Phase 1/1b, Multicenter, Open-Label, Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Jan 16, 2026
Registry last updated
Jul 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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