Biopharmaceutical company Verastem Oncology has announced a new Phase 2 clinical trial for low-grade serous cancer (LGSOC). The trial will investigate whether their investigational agents VS-6766 alone or in combination with defactinib improves outcomes for women with recurrent LGSOC.
“LGSOC is a difficult to treat disease most often diagnosed in women between the ages of 45 to 55 years. The majority of these patients experience a significant amount of pain and impact on their lives over a long period of time as response rates with current therapies have historically been low and the toxicity profiles of these agents make it difficult to keep patients on therapy. This trial represents an opportunity to further evaluate the potential for improved outcomes for patients with LGSOC.” – Dr Grisham
VS-6766 is a unique inhibitor of the RAF/MEK signaling pathway. Defactinib is a FAK inhibitor that targets malignant cells. Updated results from the ongoing Phase 1/2 UK FRAME trial reported a response rate of 41% (7 of 17) in the group of women with LGSOC treated with the combination. Of the group, 9 had KRAS-G12 mutant LGSOC – 5 of whom responded (56%). Of the 7 LGSOC responders, 5 had prior treatment with a MEK inhibitor and as of August 2020, 53% (9 of 17 patients) were still on study, with three patients on treatment for two years or more.
“Based on my experience treating patients with low-grade serous ovarian cancer in the Phase 1/2 FRAME trial, I have seen firsthand the potential for the combination of VS-6766 and defactinib, particularly in KRAS mutated tumors, which may address the significant limitations we have seen with other therapeutic approaches. This trial will further explore the encouraging response rates, durability and safety profile of VS-6766 and defactinib demonstrated in early phase studies and enable us to evaluate VS-6766 alone and in combination with defactinib to address the unmet needs of women with this specific type of ovarian cancer.” – Dr Banerjee
Locations and Recruitment
The new phase 2 trial will look to recruit 100 women with recurrent LGSOC from the US and Europe. Part A of the trial will be restricted to women with a KRAS mutations, while Part B will include women with wild type (unmutated) KRAS.
In the US the trial is being led by Dr Rachel Grisham of Memorial Sloan Kettering Cancer Center (MSKCC). Dr Grisham is the Director of Gynaecological Medical Oncology at MSKCC and an experienced low-grade serous cancer researcher.
The European lead is Dr Susana Banerjee (heading picture) who is a Medical Oncologist and Research Lead for the Gynaecology Unit at The Royal Marsden and Team Leader at The Institute of Cancer Research, London, UK.
Trial information including enrolment criteria and trial sites will be published as it comes available on the ClinicalTrials.Gov website. Pending the results of the trial, Verastem will submit a new drug application to the U.S. Food and Drug Administration (FDA) requesting accelerated approval. Currently there are no FDA approved MEK inhibitors for LGSOC.
Further details on the trial are included in the Verastem press release.
About Low Grade Serous Ovarian Cancer (LGSOC)
Low-grade serous ovarian cancer (LGSOC) is a recurrent, chemotherapy-resistant cancer with a high mortality rate. It comprises 5-10% of serous ovarian cancers and 6-8% of all ovarian cancers. There are an estimated 6,000 patients in the U.S. and 80,000 worldwide living with this disease. LGSOC is most often diagnosed in women between the ages of 45-55 years. LGSOC has a median survival of approximately 10 years, with 85% of patients experiencing recurrence and enduring severe pain and complications as the disease progresses.
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.
Defactinib (VS-6063) is an oral small molecule inhibitor of FAK and PYK2 that is currently being evaluated as a potential combination therapy for various solid tumors. Verastem has received Orphan Drug designation for defactinib in ovarian cancer in the US, EU and Australia. Preclinical research by Verastem Oncology scientists and collaborators at world-renowned research institutions has 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.