Study Of RMC-9805 In Participants With KRAS G12D-Mutant Solid Tumors

Study Overview

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

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.

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.

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

DRUG: RMC-9805
DRUG: RMC-6236

RMC-9805-001

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2023-08-31	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-08-27
First Submitted that Met QC Criteria 2023-09-08	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2025-08-28
First Posted (ESTIMATED) 2023-09-15	Results First Posted N/A	Last Verified 2025-08

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: RMC-9805 monotherapy arm Dose exploration and dose expansion	DRUG: RMC-9805 Oral Tablets
EXPERIMENTAL: RMC-9805 plus RMC-6236 combination arm Dose exploration and dose expansion	DRUG: RMC-9805 Oral Tablets DRUG: RMC-6236 Oral Tablets

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: RMC-9805 monotherapy arm

Dose exploration and dose expansion

DRUG: RMC-9805

Oral Tablets

EXPERIMENTAL: RMC-9805 plus RMC-6236 combination arm

Dose exploration and dose expansion

DRUG: RMC-9805

Oral Tablets

DRUG: RMC-6236

Oral Tablets

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
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	Cmax	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	Tmax	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	AUC	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	accumulation ratio	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	t1/2	up to 21 weeks
Overall Response Rate (ORR)	Assess per RECIST v1.1	up to 3 years
Duration of Response (DOR)	Assess per RECIST v1.1	up to 3 years
Disease Control Rate (DCR)	Assess per RECIST v1.1	up to 3 years
Time to Response (TTR)	Assess per RECIST v1.1	up to 3 years
Progression-Free Survival (PFS)	Assess per RECIST v1.1	up to 3 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Revolution Medicines, Inc.

Phone Number: 1-844-2-REVMED

Email: medinfo@RevMed.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Revolution Medicines, Inc., Revolution Medicines, Inc.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.
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.

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