RAS mutant tumors are present in about 30% of all human cancers, have historically presented a difficult treatment challenge and are often associated with significantly worse prognosis.6 Challenges associated with identifying new treatment options for these types of cancers include resistance to single agents,6 identifying tolerable combination regimens with MEK inhibitors and new RAS inhibitors in development addressing only a minority of all RAS mutated cancers.
The investigational combination of VS-6766 and defactinib has been found to be clinically active in patients with KRAS+ tumors. In an ongoing investigator-initiated Phase 1/2 FRAME study, the combination of VS-6766 and defactinib is being evaluated in patients with recurrent LGSOC, KRAS+ NSCLC and colorectal cancer. Updated data from this study presented at the 2nd Annual RAS-Targeted Drug Development Summit in September 2020 demonstrated a 56% overall response rate and long duration of therapy among patients with recurrent KRAS-G12V+ mutant LGSOC.7 Based on an observation of higher response rates seen in NSCLC patients with KRAS-G12V mutations in the study, Verastem Oncology is also exploring the role of VS-6766 and defactinib in KRAS-G12V+ NSCLC. The FRAME study was expanded in August 2020 to include new cohorts in pancreatic cancer, KRAS mutant endometrial cancer and KRAS-G12V+ NSCLC.