Study of RMC-9805 in Participants With KRASG12D-Mutant Solid Tumors

Sponsor

Revolution Medicines, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT06040541

Collaborator

(none)

290

Enrollment

Locations

Arm

34.8

Anticipated Duration (Months)

145

Patients Per Site

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer (NSCLC) Colorectal Cancer (CRC) Pancreatic Ductal Adenocarcinoma (PDAC) Advanced Solid Tumors	Drug: RMC-9805	Phase 1

Detailed Description

This is an open-label, multicenter, Phase 1/1b study of RMC-9805, monotherapy, 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 parts: Part 1- Dose-Exploration and Part 2- Dose-Expansion.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

290 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 1/1b, Multicenter, Open-Label, Study of RMC 9805 in Participants With Advanced KRASG12D-Mutant Solid Tumors

Actual Study Start Date :

Sep 7, 2023

Anticipated Primary Completion Date :

Aug 30, 2025

Anticipated Study Completion Date :

Jul 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RMC-9805 Dose exploration and dose expansion	Drug: RMC-9805 Oral Tablets

Arm

Intervention/Treatment

Experimental: RMC-9805

Dose exploration and dose expansion

Drug: RMC-9805

Oral Tablets

Outcome Measures

Primary Outcome Measures

Adverse events [Up to 3 years]
Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs, and vital signs
Dose Limiting Toxicities [21 days]
Number of participants with Dose Limiting Toxicities (DLTs)

Secondary Outcome Measures

Maximum Observed Blood Concentration (Cmax) of RMC-9805 [up to 21 weeks]
Cmax
Time to Reach Maximum Blood Concentration (Tmax) of RMC-9805 [up to 21 weeks]
Tmax
Area Under Blood Concentration Time Curve (AUC) of RMC-9805 [up to 21 weeks]
AUC
Ratio of accumulation of RMC-9805 from a single dose to steady state with repeated dosing [up to 21 weeks]
accumulation ratio of RMC-9805
Elimination Half-Life (t1/2) of RMC-9805 [up to 21 weeks]
t1/2
Overall Response Rate (ORR) [up to 3 years]
Assess per RECIST v1.1
Duration of Response (DOR) [up to 3 years]
Assess per RECIST v1.1
Disease Control Rate (DCR) [up to 3 years]
Assess per RECIST v1.1
Time to Response (TTR) [up to 3 years]
Assess per RECIST v1.1
Progression-Free Survival (PFS) [up to 3 years]
Assess per RECIST v1.1

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Pathologically documented, locally advanced or metastatic solid tumor malignancy with KRASG12D-mutations identified through deoxyribonucleic acid (DNA) sequencing or polymerase chain reaction (PCR) test
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 KRASG12D inhibitor or had prior therapy with any direct RAS-targeted therapy (eg, degraders and inhibitors)

Other inclusion/exclusion criteria may apply.