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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06040541
• Other study ID #: RMC-9805-001
• Status: Recruiting
• Phase: Phase 1
• Start date: September 7, 2023
• Est. completion date: July 31, 2026

Study information

• Verified date: September 2023
• Source: Revolution Medicines, Inc.
• Contact: Revolution Medicines, Inc.
• Phone: (650) 779-2300
• Email: CT-inquiries[@]RevMed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 290
• Est. completion date: July 31, 2026
• Est. primary completion date: August 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Advanced Solid Tumors
• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer (CRC)
• Colorectal Neoplasms
• Lung Neoplasms
• Non-small Cell Lung Cancer (NSCLC)
• Pancreatic Ductal Adenocarcinoma (PDAC)

Intervention

Drug:
• RMC-9805
Oral Tablets

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The Christ Hospital	Cincinnati	Ohio
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	NEXT Oncology Virginia	Fairfax	Virginia
United States	University of Texas, MD Anderson Cancer Center	Houston	Texas
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	START	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Revolution Medicines, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Dose Limiting Toxicities	Number of participants with Dose Limiting Toxicities (DLTs)	21 days
Secondary	Maximum Observed Blood Concentration (Cmax) of RMC-9805	Cmax	up to 21 weeks
Secondary	Time to Reach Maximum Blood Concentration (Tmax) of RMC-9805	Tmax	up to 21 weeks
Secondary	Area Under Blood Concentration Time Curve (AUC) of RMC-9805	AUC	up to 21 weeks
Secondary	Ratio of accumulation of RMC-9805 from a single dose to steady state with repeated dosing	accumulation ratio of RMC-9805	up to 21 weeks
Secondary	Elimination Half-Life (t1/2) of RMC-9805	t1/2	up to 21 weeks
Secondary	Overall Response Rate (ORR)	Assess per RECIST v1.1	up to 3 years
Secondary	Duration of Response (DOR)	Assess per RECIST v1.1	up to 3 years
Secondary	Disease Control Rate (DCR)	Assess per RECIST v1.1	up to 3 years
Secondary	Time to Response (TTR)	Assess per RECIST v1.1	up to 3 years
Secondary	Progression-Free Survival (PFS)	Assess per RECIST v1.1	up to 3 years