Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors

• Sponsor: Revolution Medicines, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05462717
• Collaborator: (none)
• Enrollment: 117
• Locations: 3
• Arm: 1
• Anticipated Duration (Months): 39
• Patients Per Site: 39
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of escalating doses of RMC-6291 (KRAS G12C(ON) inhibitor) monotherapy in adult subjects with advanced solid tumors and to identify the maximum tolerated dose (MTD), and the recommended Phase 2 dose.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer (NSCLC); Colorectal Cancer (CRC); Pancreatic Ductal Adenocarcinoma; Advanced Solid Tumor	Drug: RMC-6291	Phase 1

Detailed Description

This is an open-label, multicenter, Phase 1/1b study of RMC-6291 monotherapy in subjects with advanced KRASG12C-mutant solid tumors. The study will include 2 components: a Dose-Escalation and a Dose-Expansion. Subjects will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 117 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1/1b, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors
• Anticipated Study Start Date: Sep 1, 2022
• Anticipated Primary Completion Date: Nov 1, 2024
• Anticipated Study Completion Date: Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RMC-6291 Dose Escalation and Dose Expansion	Drug: RMC-6291; Oral tablet once or twice a day

Outcome Measures

Primary Outcome Measures

1. Adverse events [up to 3 years]

   Number of participants with adverse events

2. Dose Limiting Toxicities [The first 21 days (i.e. Cycle 1)]

   Number of participants with dose limiting toxicities

Secondary Outcome Measures

1. Maximum Observed Blood Concentration of RMC-6291 [7 Cycles]

   Cmax

2. Time to Reach Maximum Blood Concentration of RMC-6291 [7 Cycles]

   Tmax

3. Area Under Blood Concentration Time Curve of RMC-6291 [7 Cycles]

   AUC

4. Elimination Half-Life of RMC-6291 [7 Cycles]

   t1/2

5. Ratio of accumulation of RMC-6291 from a single dose to steady state with repeated dosing [7 Cycles]

   accumulation ratio

6. Overall Response Rate (ORR) [3 years]

   Overall response rate per RECIST v1.1

7. Duration of Response (DOR) [3 years]

   Duration of response per RECIST v1.1

8. Disease Control Rate (DCR) [3 years]

   Disease control rate per RECIST v1.1

9. Time to Response (TTR) [3 years]

   Time to response per RECIST v1.1

10. Progression-Free Survival (PFS) [3 years]

    Progression-free survival per RECIST v1.1

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject must be ≥18 years of age.

• Subject must have pathologically documented, locally advanced or metastatic KRASG12C-mutated solid tumor malignancy (not amenable to curative surgery) that has previously been treated with standard-of-care therapies for respective tumor types, is intolerant to, or is considered ineligible for standard-of-care anticancer treatments.

• ECOG performance status 0 or 1

• Prior treatment with a KRASG12C (OFF) inhibitor allowed for dose escalation

• Adequate organ function

Exclusion Criteria:

• Primary central nervous system (CNS) tumors

• Active brain metastases

• Known impairment of GI function that would alter the absorption

• Major surgical procedures within 28 days or non-study-related minor procedures within 7 days of treatment.

• Prior therapy with KRASG12C (ON) inhibitor

Other inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tennessee Oncology	Nashville	Tennessee	United States	37203
2	Next Oncology	San Antonio	Texas	United States	78229
3	Next Oncology Virginia	Fairfax	Virginia	United States	22031

Sponsors and Collaborators

• Revolution Medicines, Inc.

Investigators

• Study Director: Revolution Medicines, Inc., Revolution Medicines, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Revolution Medicines, Inc.
• ClinicalTrials.gov Identifier: NCT05462717
• Other Study ID Numbers: RMC-6291-001
• First Posted: Jul 18, 2022
• Last Update Posted: Aug 22, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Revolution Medicines, Inc.: RMC-6291; RAS(ON); KRAS; KRASG12C; KRASG12C(ON); Targeted therapy; Metastatic cancer; Lung Cancer; Lung Neoplasms; Thoracic Neoplasms; Non-small Cell Lung Cancer; Carcinoma, Non-Small Cell Lung; NSCLC; Colorectal Cancer; Colonic Neoplasms; CRC; Appendiceal Cancer; KRAS mutation; STK11/LKB1; KEAP1; bronchial neoplasms; respiratory tract neoplasms; neoplasms by site; neoplasms; Colon Cancer; Rectal Cancer; lung disease; respiratory tract diseases; Pancreatic Cancer; Carcinoma, Pancreatic Ductal; PDAC; Gastrointestinal Neoplasms; Intestinal Neoplasms; Esophageal cancer; Ampullary cancer; Gastric Cancer; Gynecological Cancer; Ovarian Cancer; Endometrial Cancer
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms

Study Results

No Results Posted as of Aug 22, 2022