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RecruitingNCT06128551Updated Sep 22, 2026

Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid Tumors

A Phase 1/2 interventional study of Elironrasib and Daraxonrasib in Non-Small Cell Lung Cancer (NSCLC), Colorectal Cancer and Pancreatic Ductal Adenocarcinoma, sponsored by Revolution Medicines, Inc.. Recruiting at 56 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-22.

Sponsored by Revolution Medicines, Inc. · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
534
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

This study is to evaluate the safety, tolerability, and PK profiles of Elironrasib and Daraxonrasib as monotherapies and combination therapy in patients with KRAS G12C-mutated solid tumors.

Read the detailed description

This is an open-label, multicenter, Phase 1b/2 study evaluating elironrasib and daraxonrasib, administered as monotherapy and in combination, in patients with advanced KRAS G12C-mutated solid tumors to determine the maximum tolerated dose (MTD), identify the recommended Phase 2 dose and schedule (RP2DS), and preliminarily assess antitumor activity.

The study includes a Phase 1b dose escalation and expansion of combination therapy, followed by a Phase 2 evaluation of the selected RP2DS as monotherapy and combination therapy to further assess safety and antitumor activity.

02

Conditions studied

  • Non-Small Cell Lung Cancer (NSCLC)
  • Colorectal Cancer
  • Pancreatic Ductal Adenocarcinoma

Keywords

  • RMC-6291
  • RAS (ON)
  • KRAS
  • KRASG12C
  • KRASG12C (ON)
  • Targeted therapy
  • Metastatic Cancer
  • Lung Cancer
  • Lung Neoplasms
  • Thoracic Neoplasms
  • Non-small Cell Lung Cancer
  • Carcinoma, Non-Small Cell Lung
  • NSCLC
  • Colorectal Cancer
  • Colonic Neoplasms
  • CRC
  • Appendiceal Cancer
  • KRAS mutation
  • STK11/LKB1
  • KEAP1
  • Bronchial neoplasms
  • Respiratory tract neoplasms
  • Neoplasms by site
  • Neoplasms
  • Colon Cancer
  • Rectal Cancer
  • Lung disease
  • Respiratory tract diseases
  • Pancreatic Cancer
  • Carcinoma, Pancreatic Ductal
  • PDAC
  • Gastrointestinal Neoplasms
  • Intestinal Neoplasms
  • Esophageal Cancer
  • Ampullary Cancer
  • Gastric Cancer
  • Gynecological Cancer
  • Ovarian Cancer
  • Endometrial Cancer
  • RMC-6236
  • Elironrasib
  • Daraxonrasib
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 18 years of age
  • Histology: pathologically documented, KRAS G12C-mutated, advanced or metastatic solid tumors not amendable to curative therapy

    1. Phase 1b Dose Escalation: solid tumors, previously treated
    2. Phase 1b Dose Expansion and Phase 2:

    i. NSCLC, previously treated with immunotherapy, chemotherapy, and KRAS G12C (OFF) inhibitors ii. Solid tumors, previously treated, naïve to KRAS G12C (OFF) inhibitors.

  • ECOG performance status 0 or 1
  • Adequate organ function

Exclusion criteria

Exclusion Criteria:

  • Primary central nervous system (CNS) tumors
  • Active brain metastases
  • Known impairment of GI function that would alter the absorption
  • Major surgical procedures within 28 days or non-study related minor procedures within 7 days of treatment
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
534 participants (estimated)

Study arms

  • Experimental
    Elironrasib Monotherapy

    Phase 2 only

    Drug: Elironrasib

  • Experimental
    Daraxonrasib Monotherapy

    Phase 2 only

    Drug: Daraxonrasib

  • Experimental
    Daraxonrasib + Elironrasib Combination

    Phase 1b and 2

    Drug: Elironrasib · Drug: Daraxonrasib

Interventions

  • DrugElironrasib

    oral tablets

    Also known as: RMC-6291

  • DrugDaraxonrasib

    oral tablets

    Also known as: RMC-6236

05

What researchers measure

Primary outcomes

  1. Number of patients with adverse events (AEs) in Phase 1b

    Incidence and severity of treatment-emergent AEs and serious AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5

    Time frame: Up to approximately 3 years

  2. Changes in vital signs in Phase 1b

    Number of patients with clinically significant changes in vital signs

    Time frame: Up to approximately 3 years

  3. Changes in clinical laboratory test values in Phase 1b

    Number of patients with clinically significant changes in clinical laboratory test values

    Time frame: Up to approximately 3 years

  4. Dose Limiting Toxicities in Phase 1b

    Number of participants with dose limiting toxicities

    Time frame: 21 days

  5. Changes in ECGs in Phase 1b

    Number of patients with clinically significant changes in ECGs

    Time frame: Up to approximately 3 years

  6. Overall Response Rate (ORR) in Phase 2

    Overall response rate per RECIST v1.1 as assessed by blinded independent central review (BICR)

    Time frame: Up to approximately 3 years

Secondary outcomes

  1. Maximum Observed Blood Concentration of Elironrasib and Daraxonrasib

    Cmax

    Time frame: up to 21 weeks

  2. Time to Reach Maximum Blood Concentration of Elironrasib and Daraxonrasib

    Tmax

    Time frame: up to 21 weeks

  3. Area Under Blood Concentration Time Curve of Elironrasib and Daraxonrasib

    AUC

    Time frame: up to 21 weeks

  4. Elimination Half-Life of Elironrasib and Daraxonrasib

    t1/2

    Time frame: up to 21 weeks

  5. Ratio of accumulation of Elironrasib and Daraxonrasib from a single dose to steady state with repeated dosing

    accumulation ratio

    Time frame: up to 21 weeks

  6. Overall Response Rate (ORR) in Phase 1b

    Overall response rate per RECIST v1.1

    Time frame: Up to approximately 3 years

  7. Duration of Response (DOR)

    Duration of response per RECIST v1.1

    Time frame: Up to approximately 3 years

  8. Disease Control Rate in Phase 1b

    Disease Control rate per RECIST v1.1

    Time frame: Up to approximately 3 years

  9. Time to Response (TTR) in Phase 1b

    Time to response per RECIST v1.1

    Time frame: Up to approximately 3 years

  10. Progression-Free Survival (PFS)

    Progression-free survival per RECIST v1.1

    Time frame: Up to approximately 3 years

  11. Number of patients with AEs in Phase 2

    Incidence and severity of treatment-emergent AEs and serious AEs as assessed by CTCAE v5

    Time frame: Up to approximately 3 years

  12. Changes in vital signs in Phase 2

    Number of patients with clinically significant changes in vital signs

    Time frame: Up to approximately 3 years

  13. Changes in clinical laboratory values in Phase 2

    Number of patients with clinically significant changes in clinical laboratory test values

    Time frame: Up to approximately 3 years

  14. Overall Survival (OS) in Phase 2

    OS is defined as time from enrollment until death from any cause

    Time frame: Up to approximately 3 years

06

Study locations

52 of 56 sites recruiting
  • City of Hope
    Duarte, California 91010, United States
    Withdrawn
  • UC IRVINE Health
    Orange, California 92868, United States
    Recruiting
  • UC Davis Comprehensive Cancer Center
    Sacramento, California 95817, United States
    Recruiting
  • Stanford Cancer Institute
    Stanford, California 94305, United States
    Recruiting
  • University of Colorado Cancer Center
    Aurora, Colorado 80045, United States
    Recruiting
  • Florida Cancer Specialists
    Sarasota, Florida 34232, United States
    Recruiting
  • Moffitt Cancer Center and Research Institute
    Tampa, Florida 33612, United States
    Recruiting
  • Community Health Network
    Indianapolis, Indiana 46250, United States
    Recruiting
  • Dana Farber Cancer Institute
    Boston, Massachusetts 02215, United States
    Recruiting
  • Henry Ford Cancer
    Detroit, Michigan 48202, United States
    Withdrawn
  • START Midwest
    Grand Rapids, Michigan 49546, United States
    Recruiting
  • Columbia University
    New York, New York 10032, United States
    Recruiting
  • NYU Langone Health
    New York, New York 10032, United States
    Recruiting
  • Memorial Sloan Kettering Cancer Center
    New York, New York 10065, United States
    Recruiting
  • University of Oklahoma
    Oklahoma City, Oklahoma 73104, United States
    Recruiting
  • Allegheny Health Network
    Pittsburgh, Pennsylvania 15212, United States
    Recruiting
  • Sarah Cannon Research Institue
    Nashville, Tennessee 37203, United States
    Recruiting
  • Mary Crowley Cancer Research
    Dallas, Texas 75230, United States
    Completed
  • MD Anderson
    Houston, Texas 77030, United States
    Recruiting
  • NEXT Dallas
    Irving, Texas 75039, United States
    Recruiting
  • NEXT Oncology San Antonio
    San Antonio, Texas 78229, United States
    Recruiting
  • START Texas
    San Antonio, Texas 78229, United States
    Recruiting
  • NEXT Oncology Virginia
    Fairfax, Virginia 22031, United States
    Recruiting
  • West Cancer Institute
    Angers, 49055, France
    Recruiting
  • Institut Bergonie
    Bordeaux, 33000, France
    Recruiting
  • Hospital Louise Pradel
    Bron, 69500, France
    Recruiting
  • Oscar Lambret Center of Lillle
    Lille, 59000, France
    Recruiting
  • Centre Leon Berard
    Lyon, 69373, France
    Recruiting
  • Cancer Institute of Montpellier
    Montpellier, 34298, France
    Recruiting
  • CHU Nantes
    Nantes, 44093, France
    Recruiting
  • Institute of Cancer of Strasbourg
    Strasbourg, 67033, France
    Withdrawn
  • Universitäts Klinikum Köln
    Cologne, 80937, Germany
    Recruiting
  • Klinikum Esslingen GmbH
    Esslingen am Neckar, 73730, Germany
    Recruiting
  • Krankenhaus Bethanien Moers
    Moers, 47441, Germany
    Recruiting
  • Klinkum Nurnberg Paracelsus Medical Unviersity
    Nuremberg, 90419, Germany
    Recruiting
  • Centro Ricerche Cliniche di Verona Srl
    Verona, Veneto 37134, Italy
    Recruiting
  • Department of Medical Oncology - Azienda Ospedaliero Uniersitaria delle Marche
    Ancona, 60126, Italy
    Recruiting
  • Centro Di Riferimento Oncologico
    Aviano, 33081, Italy
    Recruiting
  • Institute Romagnolo per lo Studio Tumori
    Meldola, 47014, Italy
    Recruiting
  • Niguarda Cancer Center
    Milan, 20162, Italy
    Recruiting
  • Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale"
    Naples, 80131, Italy
    Recruiting
  • San Luigi Hospital
    Orbassano, 10043, Italy
    Recruiting
  • AUSL Romagna - S.M. delle Croci Hospital
    Ravenna, 48121, Italy
    Recruiting
  • Netherlands Cancer Institute Antoni van Leeuwenhoek
    Amsterdam, 1066CX, Netherlands
    Recruiting
  • Pan American Center for Oncology Trials
    San Juan, Puerto Rico 00935, Puerto Rico
    Recruiting
  • START Barcelona - Hospital HM Nou Delfos
    Barcelona, 08023, Spain
    Recruiting
  • Institut Catala d'Oncologia Hospital
    Barcelona, 08908, Spain
    Recruiting
  • University Clinic of Navarra
    Madrid, 28027, Spain
    Recruiting
  • Fundacion MD Anderson Cancer Center
    Madrid, 28033, Spain
    Recruiting
  • START Madrid
    Madrid, 28040, Spain
    Recruiting
  • Hospital Universitario 12 de Octubre
    Madrid, 28041, Spain
    Recruiting
  • NEXT Oncology - Quirónsalud Madrid University Hospital
    Madrid, 28223, Spain
    Recruiting
  • University Clinic of Navarra
    Pamplona, 31008, Spain
    Recruiting
  • Hospital Universitario Virgen Macarena
    Seville, 41009, Spain
    Recruiting
  • La Fe University and Polytechnic Hospital
    Valencia, 46026, Spain
    Recruiting
  • Hospital Universitario Miguel Servet
    Zaragoza, 50009, Spain
    Recruiting
07

References and documents

Publications

  • Cregg J, Edwards AV, Chang S, Lee BJ, Knox JE, Tomlinson ACA, Marquez A, Liu Y, Freilich R, Aay N, Wang Y, Jiang L, Jiang J, Wang Z, Flagella M, Wildes D, Smith JAM, Singh M, Wang Z, Gill AL, Koltun ES. Discovery of Daraxonrasib (RMC-6236), a Potent and Orally Bioavailable RAS(ON) Multi-selective, Noncovalent Tri-complex Inhibitor for the Treatment of Patients with Multiple RAS-Addicted Cancers. J Med Chem. 2025 Mar 27;68(6):6064-6083. doi: 10.1021/acs.jmedchem.4c02314. Epub 2025 Mar 8. PubMed 40056080 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT06128551
Lead sponsor
Revolution Medicines, Inc.
Responsible party
Sponsor
First posted
Nov 13, 2023
Start date
Nov 14, 2023
Primary completion
Dec 2028 (estimated)
Completion
Jun 2029 (estimated)
Last update
Sep 22, 2026

Study contacts

Revolution Medicines, Inc.
Contact
medinfo@revmed.com
1-844-2-REVMED
Revolution Medicines, Inc.
study director · Revolution Medicines, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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