BO45217 - Ph 3 Divarasib vs Sotorasib or Adagrasib in NSCLC
Research type
Research Study
Full title
A PHASE III, RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF DIVARASIB VERSUS SOTORASIB OR ADAGRASIB IN PATIENTS WITH PREVIOUSLY TREATED KRAS G12CPOSITIVE ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER
IRAS ID
1009611
Contact name
Allie Bertram
Contact email
Sponsor organisation
F. Hoffmann-La Roche AG
Eudract number
2024-510908-37
Research summary
Lung cancer is the leading cause of cancer death in the world.NSCLC treated with standard of care chemotherapy and/or immunotherapy in the advanced or metastatic setting has a poor prognosis.Screening for predictive biomarkers has become increasingly important for NSCLC & has transformed patient outcomes.
Recently, several KRAS G12C inhibitors have been developed & studied in this population however, these have modest activity and there is a clear need to improve outcomes with a potentially more efficacious KRAS G12C inhibitor with acceptable safety profile & tolerability.
The aim of this study is to assess the efficacy & safety of divarasib, a (KRAS G12C) inhibitor, compared to locally approved KRAS G12C inhibitors (sotorasib or adagrasib) in patients with KRAS G12C+ advanced or metastatic non-small cell lung cancer (NSCLC) who have been previously treated with standard of care treatments in the advanced or metastatic setting.
Divarasib is an oral, covalent, anticancer therapeutic agent that selectively inhibits only the G12C mutant KRAS receptor.Sotorasib and adagrasib are small molecules that irreversibly inhibits KRAS G12C similar to divarasib.Divarasib has been shown to be 5 to 20 times as potent & up to 50 times as selective in vitro as sotorasib and adagrasib.
Divarasib has been investigated as a monotherapy & in combination with other anticancer therapies.It was found to have promising anticancer activity in patients with KRAS G12C+ solid tumours, inc NSCLC, & also demonstrated an acceptable safety profile.The important potential risks of gastrointestinal toxicities, laryngeal irritation, & elevation of hepatic transaminases were monitorable, manageable, & reversible.
This study will recruit 320 patients globally with 39 in the UK across 15 sites.
The study will last more than 4 years after the last patient is entered.
The study is sponsored by F. Hoffmann- La Roche
Research Summary; Version 1 25-Mar-2024REC name
East Midlands - Leicester South Research Ethics Committee
REC reference
24/EM/0095
Date of REC Opinion
31 May 2024
REC opinion
Further Information Favourable Opinion