D. Ross Camidge, M.D., Ph.D. from CU Anschutz Medical Campus, with final thoughts from Andrew Koustenis from Verastem Oncology, speaks about Verastem Oncology Initiates Phase 2 Registration-Directed Trial of VS-6766 and Defactinib in Recurrent Low-Grade Serous Ovarian Cancer.
BOSTON—(COMPANY WIRE)—Nov. Verastem, Inc. (Nasdaq: VSTM) (also known as Verastem Oncology), a biopharmaceutical company dedicated to advancing new medicines for cancer patients, today announced the start of a Phase 2 registration-directed clinical trial in patients with recurrent low-grade serous ovarian cancer of VS-6766, its RAF/MEK inhibitor, and defactinib, its FAK inhibitor (LGSOC).
The Phase 2 (GOG3052) study is a multicenter, parallel, randomized, open-label, adaptive, two-part multicenter trial assessing the efficacy and safety of VS-6766 alone and in combination with defactinib in patients with recurrent LGSOC.1 The first part of the study will determine the optimal regimen of either VS-6766 monotherapy or defactinib in patients with recurrent LGSOC randomized therapy. Based on objective response rate data, the determination of which regimen to take forward into the expansion phase of the trial will be made. The study's expansion process will analyze the effectiveness and safety parameters of the selected regimen. In the United States, trial enrollment is ongoing with European sites to follow. You can find more information about this research here at ClinicalTrialsgov (NCT04625270). The Company has previously announced its fruitful meeting in Q3 2020 with the Food and Drug Administration (FDA) and the support of the FDA for LGSOC's growth plan and adaptive trial design by the Company.
Professor Udai Banerji, Deputy Director of Drug Production at the Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust led the launch of the trial following the recent outcomes of two clinical trials. The first, a Phase 1 study published in The Lancet Oncology, showed that VS-6766 could be successful against a variety of types of KRAS-mutated tumors, including lung and gynecological cancers.3 The second, a Phase 1/2 study presented at the Annual Meeting 2020 of the American Association for Cancer Research (AACR), showed that the combination of an inhibitor of RAF/MEK and FAK could be advantageous for KRAS patients.
Low-Grade Serous Ovarian Cancer Around (LGSOC)
Low-grade serous ovarian cancer (LGSOC) is a high mortality rate, recurrent, chemotherapy-resistant cancer.2 It constitutes 5-10% of serous ovarian cancers and 6-8% of all ovarian cancers.2 An estimated 6,000 patients are living with this disease in the U.S. and 80,000 worldwide.5 LGSOC is most commonly diagnosed in women between the ages of 45-55.2 LGSOC has a median of 45-55 years. The quality of treatment for this condition is chemotherapy.
The oral small-molecule inhibitor of the RAF/MEK signaling pathway is VS-6766. VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK, in contrast to other MEK inhibitors in development. This unusual mechanism allows MEK signaling to be blocked by VS-6766 without the compensatory activation of MEK, which seems to limit the effectiveness of other inhibitors.
About Defactinib and Defactinib
Defactinib (VS-6063) is an oral FAK and PYK2 small molecule inhibitor currently being investigated as a possible combination therapy for different solid tumors. In the US, EU, and Australia, the Company has secured the Orphan Drug status for defactinib for ovarian cancer. The effect of FAK inhibition on improving immune response by reducing immunosuppressive cells, increasing cytotoxic T cells, and reducing stromal density, which enables tumor-killing immune cells to reach the tumor, has been identified in preclinical research by Verastem Oncology scientists and collaborators at world-renowned research institutions.
About the VS-6766/Defactinib Combination
In ~30 percent of all human cancers, RAS mutant tumors have traditionally posed a challenging treatment challenge and are often associated with a substantially worse prognosis.9 Resistance to single agents, 10 tolerable combination regimens with MEK inhibitors, and new RAS inhibitors are the difficulties associated with finding new treatment strategies for these types of cancers.
In patients with KRAS mutant tumors, the combination of VS-6766 and defactinib was found to be clinically active. The combination of VS-6766 and defactinib is being tested in patients with LGSOC, KRAS mutant NSCLC and colorectal cancer in an ongoing investigator-initiated Step 1/2 FRAME trial. At the 2nd Annual RAS-Targeted Drug Development Summit in September 2020, updated data from this study showed a 56 percent overall response rate and a long period of therapy among patients with KRAS-G12 mt LGSOC.10 Verastem will also further explore the function of VS-676 based on the observation of higher response rates seen in NSCLC patients with KRAS-G12V mutations in the study.