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

NCT ID: NCT06040541

Last Updated: 2025-08-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

604 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-07

Study Completion Date

2027-04-30

Brief Summary

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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.

Detailed Description

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This is an open-label, multicenter, Phase 1/1b study of RMC-9805, a selective and orally bioavailable KRAS G12D(ON) inhibitor, in subjects with KRASG12D-mutant solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of two arms: RMC-9805 monotherapy arm and RMC-9805 plus RMC-6236 combination arm. Both arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion.

Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

The monotherapy arm of RMC-9805; the combination arm of RMC-9805 plus RMC-6236
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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RMC-9805 monotherapy arm

Dose exploration and dose expansion

Group Type EXPERIMENTAL

RMC-9805

Intervention Type DRUG

Oral Tablets

RMC-9805 plus RMC-6236 combination arm

Dose exploration and dose expansion

Group Type EXPERIMENTAL

RMC-9805

Intervention Type DRUG

Oral Tablets

RMC-6236

Intervention Type DRUG

Oral Tablets

Interventions

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RMC-9805

Oral Tablets

Intervention Type DRUG

RMC-6236

Oral Tablets

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Revolution Medicines, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Revolution Medicines, Inc.

Role: STUDY_DIRECTOR

Revolution Medicines, Inc.

Locations

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University of California, Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status RECRUITING

Smilow Cancer Hospital (Yale University)

New Haven, Connecticut, United States

Site Status RECRUITING

Florida Cancer Specialists

Sarasota, Florida, United States

Site Status RECRUITING

Lee Moffitt Cancer Center

Tampa, Florida, United States

Site Status RECRUITING

Johns Hopkins University

Baltimore, Maryland, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

NYU Langone

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Duke Cancer Center

Durham, North Carolina, United States

Site Status RECRUITING

Carolina BioOncology Institute

Huntersville, North Carolina, United States

Site Status RECRUITING

The Christ Hospital

Cincinnati, Ohio, United States

Site Status RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status RECRUITING

Sarah Cannon Research Institute at Mary Crowley

Dallas, Texas, United States

Site Status RECRUITING

University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

START

San Antonio, Texas, United States

Site Status RECRUITING

NEXT Oncology Virginia

Fairfax, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Revolution Medicines, Inc.

Role: CONTACT

1-844-2-REVMED

References

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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.

Reference Type DERIVED
PMID: 40705880 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40056080 (View on PubMed)

Other Identifiers

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RMC-9805-001

Identifier Type: -

Identifier Source: org_study_id

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