Study FAQs

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What is LGSOC?2020-12-21T20:35:11+00:00

Low-grade serous ovarian cancer (LGSOC) is a recurrent, chemotherapy-resistant cancer with a high mortality rate.1 It comprises 5-10% of serous ovarian cancers and 6-8% of all ovarian cancers.1 There are an estimated 6,000 patients in the U.S. and 80,000 worldwide living with this disease.2 LGSOC is most often diagnosed in women between the ages of 45-55 years1 and 85% of patients experience recurrence.3 Chemotherapy is the standard of care for this disease.1

What is a KRAS mutation and how do you test for it?2020-12-21T20:37:20+00:00

All of our cells contain a gene called KRAS that regulates the signaling pathways responsible for cell proliferation, differentiation, and survival. If a mutation occurs in a KRAS gene, it may allow cancer cells to multiply out of control. KRAS mutations (KRAS+) are a common driver of cancer because KRAS is the most frequently mutated oncogene.

Testing for KRAS+ and the specific gene mutation is done by a pathologist on the actual tumor tissue.

What is VS-6766?2020-12-21T20:37:44+00:00

VS-6766 is an experimental drug that is given as a capsule twice a week for three weeks, followed by a 1-week rest period. VS-6766 is an oral small-molecule inhibitor of the RAF/MEK signaling pathway. In contrast to other MEK inhibitors in development, VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows VS-6766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors.

What is Defactinib?2020-12-21T20:38:56+00:00

Defactinib (VS-6063) is an experimental oral small molecule inhibitor of the FAK and PYK2 signaling pathways that is currently being evaluated as a potential combination therapy for various solid tumors. Verastem Oncology has received Orphan Drug Designation for defactinib in ovarian cancer in the U.S., EU and Australia. Preclinical research by Verastem Oncology scientists and collaborators at world-renowned research institutions have described the effect of FAK inhibition to enhance immune response by decreasing immuno-suppressive cells, increasing cytotoxic T cells, and reducing stromal density, which allows tumor-killing immune cells to enter the tumor. 4,5

Why use a VS-6766/Defactinib Combination?2020-12-21T20:41:09+00:00

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.

Will I be given a placebo drug?2020-12-21T20:41:32+00:00

No. This will be an open label trial, meaning that the investigator and patient will know who is being treated with which medication. Both patient groups will be given the experimental drug. One group or arm will get just VS-6766. The other group will get VS-6766 in combination with defactinib.

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1 Grisham, R. Low grade serous carcinoma of the ovary. Oncology. 2016. 30(7):650-652. Available at: Accessed December 3, 2020.
2 Slomovitz, Gourley, Carey, Malpica, Shih, Huntsman, Fader., Grisham et al, Low-Grade serous ovarian cancer: State of the Science; Gynecol Oncol; 2020.
3 Corrado G, Salutari V, Palluzzi E, Distefano MG, Scambia G, Ferrandina G. Optimizing treatment in recurrent epithelial ovarian cancer. Expert Rev Anticancer Ther. 2017;17:1147-1158. doi: 10.1080/14737140.2017.1398088.
4 Chénard-Poirier, M. et al. Results from the biomarker-driven basket trial of RO5126766 (CH5127566), a potent RAF/MEK inhibitor, in RAS- or RAF-mutated malignancies including multiple myeloma. Journal of Clinical Oncology 2017: 35. 10.1200/JCO.2017.35.15_suppl.2506.
5 Phase I Trial of VS-6063 and RO5126766. (FRAME). Available at: Accessed November 24, 2020.
6 Baines, A. T., Xu, D., & Der, C. J. (2011). Inhibition of Ras for cancer treatment: the search continues. Future medicinal chemistry, 3(14), 1787–1808.
7 Verastem Press Release. Verastem Oncology Announces Presentation of Updated Phase 1/2 FRAME Study Data at the 2nd Annual RAS-Targeted Drug Development Summit. September 16, 2020. Available at: Accessed November 24, 2020.