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

• ClinicalTrials.gov Identifier: NCT05462717
• Recruitment Status: Recruiting
• First Posted: July 18, 2022
• Last Update Posted: April 19, 2024
• Sponsor: Revolution Medicines, Inc.
• Information provided by (Responsible Party): Revolution Medicines, Inc.

Tracking Information

• First Submitted Date: July 11, 2022
• First Posted Date: July 18, 2022
• Last Update Posted Date: April 19, 2024
• Actual Study Start Date: September 19, 2022
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 13, 2022)

• Adverse events [ Time Frame: up to 3 years ]
  Number of participants with adverse events
• Dose Limiting Toxicities [ Time Frame: The first 21 days (i.e. Cycle 1) ]
  Number of participants with dose limiting toxicities

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 13, 2022)

• Maximum Observed Blood Concentration of RMC-6291 [ Time Frame: 7 Cycles ]
  Cmax
• Time to Reach Maximum Blood Concentration of RMC-6291 [ Time Frame: 7 Cycles ]
  Tmax
• Area Under Blood Concentration Time Curve of RMC-6291 [ Time Frame: 7 Cycles ]
  AUC
• Elimination Half-Life of RMC-6291 [ Time Frame: 7 Cycles ]
  t1/2
• Ratio of accumulation of RMC-6291 from a single dose to steady state with repeated dosing [ Time Frame: 7 Cycles ]
  accumulation ratio
• Overall Response Rate (ORR) [ Time Frame: 3 years ]
  Overall response rate per RECIST v1.1
• Duration of Response (DOR) [ Time Frame: 3 years ]
  Duration of response per RECIST v1.1
• Disease Control Rate (DCR) [ Time Frame: 3 years ]
  Disease control rate per RECIST v1.1
• Time to Response (TTR) [ Time Frame: 3 years ]
  Time to response per RECIST v1.1
• Progression-Free Survival (PFS) [ Time Frame: 3 years ]
  Progression-free survival per RECIST v1.1

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors
• 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
• 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.
• 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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-Small Cell Lung Cancer (NSCLC)
• Colorectal Cancer (CRC)
• Pancreatic Ductal Adenocarcinoma
• Advanced Solid Tumor

Intervention

Drug: RMC-6291

Oral tablet once or twice a day

Study Arms

Experimental: RMC-6291

Dose Escalation and Dose Expansion

Intervention: Drug: RMC-6291

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 9, 2024): 222
• Original Estimated Enrollment (submitted: July 13, 2022): 117
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Revolution Medicines, Inc.; (650) 779-2300; CT-inquiries@RevMed.com

• Listed Location Countries: Australia, Czechia, France, Italy, Korea, Republic of, Malaysia, Poland, Serbia, Singapore, Spain, Taiwan, Thailand, United States

Administrative Information

• NCT Number: NCT05462717
• Other Study ID Numbers: RMC-6291-001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Revolution Medicines, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Revolution Medicines, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Revolution Medicines, Inc.
• Verification Date: April 2024