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

NCT06128551 | Recruiting Phase 1 FDA Drug

• 1 other identifier: RMC-6291-101
• Study Type: interventional
• Target: 534
• Locations: 7 countries
• Sites: 53

Brief 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.

Conditions

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

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

Outcome Measures

Primary Outcomes (6)

• 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

  Up to approximately 3 years

• Changes in vital signs in Phase 1b

  Number of patients with clinically significant changes in vital signs

  Up to approximately 3 years

• Changes in clinical laboratory test values in Phase 1b

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

  Up to approximately 3 years

• Dose Limiting Toxicities in Phase 1b

  Number of participants with dose limiting toxicities

  21 days

• Changes in ECGs in Phase 1b

  Number of patients with clinically significant changes in ECGs

  Up to approximately 3 years

• Overall Response Rate (ORR) in Phase 2

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

  Up to approximately 3 years

Secondary Outcomes (14)

• Maximum Observed Blood Concentration of Elironrasib and Daraxonrasib

  up to 21 weeks

• Time to Reach Maximum Blood Concentration of Elironrasib and Daraxonrasib

  up to 21 weeks

• Area Under Blood Concentration Time Curve of Elironrasib and Daraxonrasib

  up to 21 weeks

• Elimination Half-Life of Elironrasib and Daraxonrasib

  up to 21 weeks

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

  up to 21 weeks

Study Arms (3)

Elironrasib Monotherapy

EXPERIMENTAL

Phase 2 only

Drug: Elironrasib

Daraxonrasib Monotherapy

EXPERIMENTAL

Phase 2 only

Drug: Daraxonrasib

Daraxonrasib + Elironrasib Combination

EXPERIMENTAL

Phase 1b and 2

Drug: Elironrasib; Drug: Daraxonrasib

Interventions

Elironrasib DRUG

oral tablets

Also known as: RMC-6291

Daraxonrasib + Elironrasib Combination; Elironrasib Monotherapy

Daraxonrasib DRUG

oral tablets

Also known as: RMC-6236

Daraxonrasib + Elironrasib Combination; Daraxonrasib Monotherapy

Eligibility Criteria

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

You may qualify if:

• years of age
• Histology: pathologically documented, KRAS G12C-mutated, advanced or metastatic solid tumors not amendable to curative therapy
• Phase 1b Dose Escalation: solid tumors, previously treated
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Revolution Medicines, Inc.: lead

Study Sites (53)

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

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

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

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, 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

Related Publications (1)

• 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.

  PMID: 40056080 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Neoplasm Metastasis; Lung Neoplasms; Thoracic Neoplasms; Colonic Neoplasms; Appendiceal Neoplasms; Bronchial Neoplasms; Respiratory Tract Neoplasms; Neoplasms by Site; Neoplasms; Rectal Neoplasms; Lung Diseases; Respiratory Tract Diseases; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Gastrointestinal Neoplasms; Intestinal Neoplasms; Esophageal Neoplasms; Stomach Neoplasms; Ovarian Neoplasms; Endometrial Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cecal Neoplasms; Cecal Diseases; Bronchial Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Ductal, Lobular, and Medullary; Head and Neck Neoplasms; Esophageal Diseases; Stomach Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases

Study Officials

• Revolution Medicines, Inc.

  Revolution Medicines, Inc.

  STUDY DIRECTOR

Central Study Contacts

Revolution Medicines, Inc.

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: None (Open Label)
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2023
• First Posted: November 13, 2023
• Study Start: November 14, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (21); DE (4); NL (1); PR (1); IT (7); ES (11); FR (8)