Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors
- Registration Number
- NCT03634982
- Lead Sponsor
- Revolution Medicines, Inc.
- 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).
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 133
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description RMC-4630 RMC-4630 RMC-4630 for oral administration
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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
Trial Locations
- Locations (12)
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
Sarah Cannon Research Institute - Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
City of Hope
🇺🇸Duarte, California, United States
UC Irvine - Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
University of Oklahoma - Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Honor Health Research Institute
🇺🇸Scottsdale, Arizona, United States
UC Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Moffit Cancer Center
🇺🇸Tampa, Florida, United States
University of Texas at Austin - Dell Medical School
🇺🇸Austin, Texas, United States