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

Sponsor

Revolution Medicines, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03634982

Collaborator

Sanofi (Industry)

175

Enrollment

Locations

Arm

50.1

Anticipated Duration (Months)

14.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: RMC-4630	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

175 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 28, 2018

Anticipated Primary Completion Date :

Jul 31, 2022

Anticipated Study Completion Date :

Nov 30, 2022

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: RMC-4630

RMC-4630 for oral administration

Drug: RMC-4630

RMC-4630 for oral administration

Outcome Measures

Primary Outcome Measures

Number of participants with adverse events (AEs) [up to 3 years]
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
Number of participants with dose limiting toxicities (DLTs) [28 days]
Incidence and nature of DLTs with RMC-4630 monotherapy

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Honor Health Research Institute	Scottsdale	Arizona	United States	85258
2	City of Hope	Duarte	California	United States	91010
3	UC Irvine - Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
4	UC Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
5	UC San Francisco - Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
6	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
7	Sarah Cannon Research Institute - Florida Cancer Specialists	Sarasota	Florida	United States	34232
8	Moffit Cancer Center	Tampa	Florida	United States	33612
9	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
10	University of Oklahoma - Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
11	Sarah Cannon Research Institute - Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
12	University of Texas at Austin - Dell Medical School	Austin	Texas	United States	78712