Study of RMC-9805 in Participants With KRAS G12D-Mutant Solid Tumors

NCT06040541 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: RMC-9805-001
• Study Type: interventional
• Target: 604
• Locations: 1 country
• Sites: 17

Brief Summary

This study is to evaluate the safety and tolerability of RMC-9805 as monotherapy and in combination with RMC-6236 in adults with KRAS G12D-mutant solid tumors.

Conditions

Non-small Cell Lung Cancer (NSCLC); Colorectal Cancer (CRC); Pancreatic Ductal Adenocarcinoma (PDAC); Advanced Solid Tumors

Keywords

KRAS G12D (ON); NSCLC; CRC; PDAC; Non-small Cell Lung Cancer; Lung Cancer; Colorectal Cancer; Colon Cancer; Pancreatic Cancer; Metastatic Cancer; Pancreatic Ductal Adenocarcinoma; Pancreatic Neoplasms; Colorectal Neoplasms; Gastrointestinal Neoplasms; KRAS; Colonic Neoplasms

Outcome Measures

Primary Outcomes (2)

• Adverse events

  Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs, and vital signs

  Up to 3 years

• Dose Limiting Toxicities

  Number of participants with Dose Limiting Toxicities (DLTs)

  21 days

Secondary Outcomes (10)

• Maximum Observed Blood Concentration (Cmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Cmax of RMC-6236 in combination with RMC-9805

  up to 21 weeks

• Time to Reach Maximum Blood Concentration (Tmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Tmax of RMC-6236 in combination with RMC-9805

  up to 21 weeks

• Area Under Blood Concentration Time Curve (AUC) of RMC-9805 as monotherapy and in combination with RMC-6236, and AUC of RMC-6236 in combination with RMC-9805

  up to 21 weeks

• Ratio of accumulation of RMC-9805 from a single dose to steady state with repeated dosing as monotherapy and in combination with RMC-6236, and ratio of accumulation of RMC-6236 in combination with RMC-9805

  up to 21 weeks

• Elimination Half-Life (t1/2) of RMC-9805 as monotherapy and in combination with RMC-6236, and t1/2 of RMC-6236 in combination with RMC-9805

  up to 21 weeks

Study Arms (2)

RMC-9805 monotherapy arm

EXPERIMENTAL

Dose exploration and dose expansion

Drug: RMC-9805

RMC-9805 plus RMC-6236 combination arm

EXPERIMENTAL

Dose exploration and dose expansion

Drug: RMC-9805; Drug: RMC-6236

Interventions

RMC-9805 DRUG

Oral Tablets

RMC-9805 monotherapy arm; RMC-9805 plus RMC-6236 combination arm

RMC-6236 DRUG

Oral Tablets

RMC-9805 plus RMC-6236 combination arm

Eligibility Criteria

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

You may qualify if:

• Pathologically documented, locally advanced or metastatic solid tumor with a KRAS G12D-mutation
• Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage
• ECOG performance status 0 or 1
• Adequate organ function

You may not qualify if:

• Primary central nervous system (CNS) tumors
• Known or suspected leptomeningeal or active brain metastases or spinal cord compression
• Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication
• Participant was previously treated with an investigational KRAS G12D inhibitor, pan- or multi-RAS inhibitor, or had prior therapy with any direct RAS-targeted therapy (eg, degraders and inhibitors)

Sponsors & Collaborators

• Revolution Medicines, Inc.: lead

Study Sites (17)

University of California, Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

Smilow Cancer Hospital (Yale University)

New Haven, Connecticut, 06511, United States

RECRUITING

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

RECRUITING

Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21287, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

NYU Langone

New York, New York, 10016, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Duke Cancer Center

Durham, North Carolina, 27710, United States

RECRUITING

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

RECRUITING

The Christ Hospital

Cincinnati, Ohio, 45219, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

Sarah Cannon Research Institute at Mary Crowley

Dallas, Texas, 75230, United States

RECRUITING

University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

START

San Antonio, Texas, 78229, United States

RECRUITING

NEXT Oncology Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Related Publications (2)

• Weller C, Burnett GL, Jiang L, Chakraborty S, Zhang D, Vita NA, Dilly J, Kim E, Maldonato B, Seamon K, Eilerts DF, Milin A, Marquez A, Spradlin J, Helland C, Gould A, Ziv TB, Dinh P, Steele SL, Wang Z, Mu Y, Chugh S, Feng H, Hennessey C, Wang J, Roth J, Rees M, Ronan M, Wolpin BM, Hahn WC, Holderfield M, Wang Z, Koltun ES, Singh M, Gill AL, Smith JAM, Aguirre AJ, Jiang J, Knox JE, Wildes D. A neomorphic protein interface catalyzes covalent inhibition of RASG12D aspartic acid in tumors. Science. 2025 Jul 24;389(6758):eads0239. doi: 10.1126/science.ads0239. Epub 2025 Jul 24.

  PMID: 40705880 DERIVED

• 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; Lung Neoplasms; Colonic Neoplasms; Pancreatic Neoplasms; Neoplasm Metastasis; Gastrointestinal Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The monotherapy arm of RMC-9805; the combination arm of RMC-9805 plus RMC-6236

Study Record Dates

• First Submitted: August 31, 2023
• First Posted: September 15, 2023
• Study Start: September 7, 2023
• Primary Completion: April 30, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: August 28, 2025

Record last verified: 2025-08

Locations

US (17)