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Brief Title: Dose-Escalation/Expansion of RMC-4630 and Cobimetinib in Relapsed/Refractory Solid Tumors and RMC-4630 and Osimertinib in EGFR Positive Locally Advanced/Metastatic NSCLC

Ph1b/2 Open-Label,Multicenter Dose-Esc & Dose-Exp Study of Combo RMC4630 & Cobimetinib in Participants w/Relapsed/Refractory Solid Tumors & Ph1b Study of RMC4630 w/Osimertinib in Participants w/EGFR Mutation+,Locally Adv or Meta NSCLC


  • Org Study ID: RMC-4630-02
  • Secondary ID: N/A
  • NCT ID: NCT03989115
  • Sponsor: Revolution Medicines, Inc.


The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of RMC-4630 and cobimetinib in adult participants with relapsed/refractory solid tumors with specific genomic aberrations and to identify the recommended Phase 2 dose (RP2D); and to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of RMC-4630 and osimertinib in adult participants with EGFR mutation-positive locally advanced or metastatic NSCLC.


This open-label, phase 1b/2 dose-escalation and dose-expansion study is designed to evaluate the safety and maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of RMC-4630 in combination with cobimetinib in participants with relapsed/refractory solid tumors; and of RMC-4630 in combination with osimertinib in adult participants with EGFR mutation-positive locally advanced or metastatic NSCLC.

  • Overall Status
  • Start Date
    July 2, 2019
  • Phase
  • Study Type


Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A


  • Solid Tumor


Inclusion Criteria:
* Age ≥18 years

- * For RMC-4630 + Cobimetinib only - Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anti-cancer treatments including approved drugs for oncogenic drivers in their tumor type.

- * For RMC-4630 + Osimertinib only - Locally advanced or metastatic EGFR mutant NSCLC not amenable to curative surgery or radiotherapy

- * For RMC-4630 + Cobimetinib only - Participants must have one of the following genotypic aberrations: KRAS mutations and amplifications, BRAF Class 3 mutations, or NF1 LOF mutations

- * For RMC-4630 + Osimertinib only - Evidence of radiological documentation of progression with osimertinib monotherapy or an osimertinib containing regimen. Participants should not be considered a current candidate for 1st generation EGFR TKI's by the investigator.

- * Eastern Cooperative Oncology Group (ECOG) performance status of ≤1

- * Adequate hematological, hepatic, and renal function

- * Capable of giving signed informed consent form (ICF). Willing and able to compile with study requirements and restrictions

- * Life expectancy >12 weeks

- * Female of childbearing potential and males with partners of childbearing potential must comply with effective contraception criteria .
Exclusion Criteria:
* Primary central nervous system (CNS) tumors.

- * Known or suspected leptomeningeal or brain metastases or spinal cord compression.

- * For RMC-4630 + osimertinib arm only - Known or suspected Small cell, squamous, or pleomorphic lung transformations

- * 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 or 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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No


Name: Revolution Medicines, Inc.

Role: Study Director

Affiliation: Revolution Medicines, Inc.

Overall Contact

Name: N/A

Phone: N/A

Email: N/A


Facility Status Contact