Dr. Grisham on the Combination of VS-6766 With Defactinib in Ovarian Cancer

Rachel N. Grisham, MD, section head of Ovarian Cancer, director of Gynecologic Medical Oncology, Memorial Sloan Kettering Cancer Center, discusses the rationale to explore the combination of VS-6766 (formerly CH5126766) and defactinib in patients with low-grade serous ovarian cancer.

Patients with low-grade serous ovarian cancer and those with the more common high-grade serious ovarian cancer differ in molecular distinction, Grisham explains. Low-grade serious ovarian cancer accounts for less than 10% of all ovarian cancer cases, according to Grisham. Unlike high-grade serious ovarian cancer, low-grade serious ovarian cancers are usually p53 wild-type and the most commonly observed alterations affect the MAPK pathway, Grisham explains.

KRAS mutations primarily affect this pathway, but other less common mutations such as BRAF V600E mutations and NF1 mutations have also been observed, Grisham adds. Based on this molecular profile, there has been interest in examining the use of targeted therapies in the treatment of the disease, Grisham says. This is particularly because patients with low-grade serious ovarian cancer have demonstrated historically low response rates to standard systemic therapies like chemotherapy and endocrine therapies, Grisham concludes.