RMC-4630 and Cobimetinib Dosing in Relapsed/Refractory Solid Tumours
Research type
Research Study
Full title
A Phase 1b/2, Open-Label, Multicenter Dose-Escalation and Dose-Expansion Study of the Combination of RMC-4630 with Cobimetinib in Adult Participants with Relapsed/Refractory Solid Tumors and a Phase 1b Study of RMC-4630 with Osimertinib in Participants with Epidermal Growth Factor Receptor Mutation Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer
IRAS ID
283987
Contact name
Colin Lindsay
Contact email
Sponsor organisation
Revolution Medicines, Inc.
Eudract number
2020-002087-31
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
138359, IND
Duration of Study in the UK
1 years, 7 months, 28 days
Research summary
Most patients with mutations that cause overactivation of the RAS-MAPK cell communication pathway have a poor prognosis. The combination of inhibiting a new target of an early part of this pathway called SHP2 together with inhibiting a later part of this cell pathway called MEK1/2, provides a potentially novel targeted treatment for patients with relapsed or refractory solid tumours with the above mutations.
RMC-4630 is an oral SHP2 inhibitor. Cobimetinib is an oral MEK inhibitor. In animal studies, RMC 4630 and cobimetinib together achieved significant and a combined greater anti-tumour effect. These anti-tumour effects were observed at lower doses as compared to those required for maximal anti-tumour activity for either agent alone and were tolerated. Intermittent dosing of RMC-4630 in combination with continuous cobimetinib showed improved tolerability and comparable anti-tumour activity relative to equivalent daily RMC-4630.
The purpose of the study arm taking place in the UK is to evaluate the safety and maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of RMC-4630 and cobimetinib in participants with relapsed/refractory solid tumours as well as to assess the initial efficacy in participants with tumours carrying specific mutations that result in hyperactivation of the RAS-MAPK pathway. All UK participants will receive RMC-4630 and cobimetinib.
This study is sponsored by Revolution Medicines, Inc. Approximately 144 patients will take part worldwide taking the study medicines for up to 1-3 years. These will be given in 28-day cycles, with hospital visits around 6 times in the first cycle, and then twice or once in subsequent cycles, a 30 day follow up visit after treatment and telephone contact every 3 months until the end of the study. Assessments will include physical and eye examinations, blood tests, ECG and ECHO or MUGA heart tests, MRI or CT scans, and tumour biopsies.
REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
21/YH/0088
Date of REC Opinion
14 May 2021
REC opinion
Further Information Favourable Opinion