Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors

A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of RMC-4630 Monotherapy in Adult Participants With Relapsed/Refractory Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of escalating doses of RMC-4630 monotherapy in adult participants with relapsed/refractory solid tumors and to identify the recommended Phase 2 dose (RP2D).

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: RMC-4630

Detailed Description

This is an open-label, multicenter, Phase 1 study of oral RMC-4630 monotherapy in participants with advanced relapsed or refractory solid tumors. The study will include 2 components: 1) a Dose-Escalation Component for participants with relapsed or refractory solid tumors and 2) a Dose-Expansion Component for participants with relapsed or refractory solid tumors harboring certain specific mutations/rearrangements that result in hyperactivation of the RAS-MAPK pathway. Participants 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
• Enrollment (Actual): 133
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Honor Health Research Institute
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Orange, California, United States, 92868
      • UC Irvine - Chao Family Comprehensive Cancer Center
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
    • San Francisco, California, United States, 94115
      • UC San Francisco - Helen Diller Family Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Florida
    • Sarasota, Florida, United States, 34232
      • Sarah Cannon Research Institute - Florida Cancer Specialists
    • Tampa, Florida, United States, 33612
      • Moffit Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma - Stephenson Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute - Tennessee Oncology, PLLC
  • Texas
    • Austin, Texas, United States, 78712
      • University of Texas at Austin - Dell Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant (male or female) ≥18 years of age
• Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anticancer treatments including approved drugs for oncogenic drivers in their tumor type
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Participants in the Dose-Expansion Component must have one of the following genotypic aberrations: KRAS amplifications, KRASG12C (NSCLC), BRAF Class 3, or NF1 LOF (NSCLC and gynecological cancers) mutations
• Adequate hematologic, hepatic and renal function
• Participant able to understand and voluntarily sign the informed consent form (ICF) and able to comply with the study visit schedule and other protocol requirements.
• Participants willing to agree to not father a child/become pregnant and comply with effective contraception criteria

Exclusion Criteria:

• Known or suspected leptomeningeal or brain metastases or spinal cord compression
• Primary central nervous system (CNS) tumors
• Clinically significant cardiac disease
• Active, clinically significant interstitial lung disease or pneumonitis
• History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO
• Known HIV infection
• Active/chronic hepatitis B or C infection
• Any other unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy
• Females who are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RMC-4630; RMC-4630 for oral administration	Drug: RMC-4630; RMC-4630 for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	Incidence, nature, and severity of treatment-emergent AEs and serious AEs, including incidence and severity of findings in laboratory values and vital signs for RMC-4630 monotherapy	up to 3 years
Number of participants with dose limiting toxicities (DLTs)	Incidence and nature of DLTs with RMC-4630 monotherapy	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Peak plasma concentration of RMC-4630	up to 3 years
Tmax	Time to achieve peak plasma concentration of RMC-4630	up to 3 years
Area Under the Curve (AUC)	Area under the plasma concentration time curve of RMC-4630	up to 3 years
t1/2	Elimination half-life of RMC-4630	up to 3 years
Accumulation Ratio	Ratio of accumulation of RMC-4630 from a single dose to steady state with repeated dosing	up to 3 years
Overall Response Rate (ORR)	Overall response rate of RMC-4630 per RECIST v1.1	up to 3 years
Duration of Response (DOR)	Duration of response of RMC-4630 per RECIST v1.1	up to 3 years

Collaborators and Investigators

• Sponsor: Revolution Medicines, Inc.
• Collaborators: Sanofi
• Investigators: Study Director: Revolution Medicines, Inc., Revolution Medicines, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2018
• Primary Completion (Anticipated): March 31, 2023
• Study Completion (Anticipated): May 31, 2023

Study Registration Dates

• First Submitted: August 10, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 17, 2018

Study Record Updates

• Last Update Posted (Actual): September 1, 2022
• Last Update Submitted That Met QC Criteria: August 31, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; NSCLC; Neoplasms; Gastrointestinal Diseases; Digestive System Diseases; EGFR; bladder cancer; ovarian cancer; Lung Diseases; SHP2; melanoma; Carcinoma, Non-Small-Cell Lung; advanced solid tumor; Esophageal Diseases; Thoracic Neoplasms; PTPN11; cervical cancer; Head and Neck Neoplasms; Bronchial Neoplasms; Neoplasms, Glandular and Epithelial; skin cancer; Esophageal Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; advanced solid malignancies; endometrium/uterus cancer; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Respiratory Tract Neoplasms; KRAS G12; BRAF Class 3; NF1 LOF
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: RMC-4630-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No