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

Phase 1RecruitingNCT06040541

Revolution Medicines, Inc.604 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

604

Conditions

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

Interventions

RMC-9805DRUG

Oral Tablets

RMC-6236DRUG

Oral Tablets

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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) Other inclusion/exclusion criteria may apply.

Locations (17)

University of California, Davis Comprehensive Cancer Center

Sacramento, California, United States

RECRUITING

Outcomes

Primary Outcomes

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

Time frame: Up to 3 years

Dose Limiting Toxicities

Number of participants with Dose Limiting Toxicities (DLTs)

Time frame: 21 days

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: up to 21 weeks

Central Contacts

Revolution Medicines, Inc.

CONTACT

1-844-2-REVMED medinfo@RevMed.com

Data from ClinicalTrials.gov

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