A recent international study has brought a new anticancer drug that targets a mutation in a gene called KRAS closer to clinical application. The findings reveal few serious side effects in individuals affected by cancer and were published in the New England Journal of Medicine. The study involved 35 institutions across 12 countries, with Princess Margaret Cancer Centre Clinician Investigator Dr. Adrian Sacher as the lead author.
KRAS plays a role in helping cells grow and divide, and when its function is altered it can drive normal cells to become cancerous. KRAS is one of the most common genes that are mutated in solid cancers, but until recently treatments were not available that could directly target this gene pathway.
Genentech, the sponsor of the study, developed the drug divarasib to target a specific type of KRAS mutation found in 12-14% of patients with non-small-cell lung cancer and 4% of patients with colorectal cancer. This new agent may provide a more effective, targeted therapy for patients with this particular change in their KRAS gene, and early indications are that it may be more effective than the other early attempts to target KRAS.
This early phase study tested the safety of divarasib in patients with cancer, and found few serious side effects, with only 3% of patients stopping the medication because of adverse side effects.
The response of patients’ cancers to divarasib was impressive, with over half of patients with metastatic non-small-cell lung cancer and nearly a third of those with colon cancer showing a response to treatment.
“This study demonstrates impressive clinical activity and tolerability for divarasib in tumors with KRAS G12C mutations. We are conducting randomized studies of divarasib to confirm these results and are also evaluating divarasib as a combination therapy with other novel drugs,” explains Dr. Sacher. “But that said, divarasib has demonstrated the best response rate for a KRAS inhibitor to date and the team is excited by these results.”
“We are hopeful that this study constitutes the first step in developing new treatment strategies based around selective KRAS inhibitors that lead to new treatment options for our patients with lung, colon and other solid tumors,” says Dr. Sacher.
Cancer therapies often involve side effects, such as hair loss and nausea. This study evaluated the side effects of a new drug, the first step in getting regulatory approval.
This work was supported by Genentech, Fundació La Caixa, the UK National Institute of Health Research and the Princess Margaret Cancer Foundation. The study was sponsored and designed by Genentech. Dr. Adrian Sacher is an Assitant Professor in the Departments of Medicine & Immunology at the University of Toronto.
Sacher S, LoRusso P, Patel MR, Miller WH, Garralda E, Forster MD, Santoro A, Falcon A, Kim TW, Paz-Ares L, Bowyer S, de Miguel M, Han S-W, Krebs MG, Lee J-S, Cheng ML, Arbour K, Massarelli E, Choi Y, Shi Z, Mandlekar S, Lin MT, Royer-Joo S, Chang J, Dharia NV, Schutzman JL, Desai J, for the GO42144 Investigator and Study Group. Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation. N Engl J Med. 2023 Aug 23. DOI: 10.1056/NEJMoa2303810.