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

Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03634982
• Other study ID #: RMC-4630-01
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 28, 2018
• Est. completion date: May 31, 2023

Study information

• Verified date: September 2021
• Source: Revolution Medicines, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 133
• Est. completion date: May 31, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• RMC-4630
RMC-4630 for oral administration

Locations

Country	Name	City	State
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	University of Texas at Austin - Dell Medical School	Austin	Texas
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	City of Hope	Duarte	California
United States	Sarah Cannon Research Institute - Tennessee Oncology, PLLC	Nashville	Tennessee
United States	University of Oklahoma - Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	UC Irvine - Chao Family Comprehensive Cancer Center	Orange	California
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	UC San Francisco - Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Sarah Cannon Research Institute - Florida Cancer Specialists	Sarasota	Florida
United States	Honor Health Research Institute	Scottsdale	Arizona
United States	Moffit Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Revolution Medicines, Inc.	Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of participants with dose limiting toxicities (DLTs)	Incidence and nature of DLTs with RMC-4630 monotherapy	28 days
Secondary	Cmax	Peak plasma concentration of RMC-4630	up to 3 years
Secondary	Tmax	Time to achieve peak plasma concentration of RMC-4630	up to 3 years
Secondary	Area Under the Curve (AUC)	Area under the plasma concentration time curve of RMC-4630	up to 3 years
Secondary	t1/2	Elimination half-life of RMC-4630	up to 3 years
Secondary	Accumulation Ratio	Ratio of accumulation of RMC-4630 from a single dose to steady state with repeated dosing	up to 3 years
Secondary	Overall Response Rate (ORR)	Overall response rate of RMC-4630 per RECIST v1.1	up to 3 years
Secondary	Duration of Response (DOR)	Duration of response of RMC-4630 per RECIST v1.1	up to 3 years