Dr. Banerji on the Clinical Activity of VS-6766/Defactinib in KRAS-Mutant Tumors

Udai Banerji, MD, the National Institute for Health Research Professor of Molecular Cancer Pharmacology, honorary consultant in medical oncology and deputy director of the Drug Development Unit at the Royal Marsden NHS Foundation Trust, discusses the results from a phase 1 trial with the combination of VS-6766 (CH5126766) and defactinib in KRAS-mutant tumors.

The combination of VS-6766 and defactinib has shown preliminary signals of activity in patients with KRAS-mutant tumors, explains Banerji. According to data from a phase 1 trial presented at the 2020 AACR Virtual Annual Meeting I, 67% of patients with KRAS-mutant low-grade serous ovarian carcinoma (n = 6) responded to the combination of VS-6766 and defactinib.

A number of patients who responded to the combination had previously received a MEK inhibitor, suggesting that the combination can overcome MEK-mediated resistance, says Banerji. Among patients with KRAS-mutant non—small cell lung cancer, investigators reported 2 responses.

Moreover, some patients reached the 24-week cutoff, which could be a sign of the combination’s activity and tolerability. Given the signals reported in this trial, investigators are hoping to expand the trial to a larger number of patients, as well as those with KRAS-mutant colorectal cancer and KRAS-mutant pancreatic cancer, concludes Banerji.