Verastem Reports Positive Results in Updated Phase 2 Results of Experimental Therapy in Rare Form of Ovarian Cancer

Rare Daily Staff

Verastem Oncology reported updated data from Part A of the ongoing registration-directed RAMP 201 trial evaluating the safety and efficacy of avutometinib alone and in combination with defactinib among patients with recurrent low-grade serous ovarian cancer.

In the RAMP 201 study, treatment with the combination of avutometinib and defactinib resulted in an objective response rate (ORR) of 45 percent and tumor shrinkage in 86 percent of evaluable patients.

Safety and tolerability continued to be favorable and consistent with previously reported data. These data, which will be presented at the American Society of Clinical Oncology Annual Meeting, build on the Breakthrough Therapy Designation granted by the U.S. Food and Drug Administration for the combination in recurrent low-grade serous ovarian cancer (LGSOC).

LGSOC is a highly recurrent, chemotherapy-resistant cancer, associated with slow tumor growth and high mortality rate. Approximately 6,000 women in the U.S. and 80,000 worldwide are living with this disease. Mutations in the KRAS gene are present in 30 percent of cases of LGSOC. LGSOC is most often diagnosed in women between the ages of 45-55 years and has a median survival of approximately ten years. The majority of patients experience severe pain and complications as the disease progresses. Chemotherapy is the standard of care for this disease, with limited treatment options currently available.

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. Defactinib is a best-in-class selective FAK inhibitor that has been studied as a monotherapy and in combination in patients with solid tumors.

RAMP 201 is an international registration-directed phase 2 study evaluating the safety and efficacy of avutometinib alone and in combination with defactinib among patients with recurrent LGSOC. The key objectives of Part A (selection phase) of the RAMP 201 LGSOC study were to select avutometinib monotherapy or the combination of avutometinib and defactinib as the go forward regimen to be studied in Part B (expansion phase) of the study, and to assess efficacy in both KRAS mutant and KRAS wild type LGSOC. These data reinforce the selection of the combination of avutometinib with defactinib as the go forward regimen regardless of KRAS status, and target enrollment has been achieved in both Part A and Part B.

“These results demonstrate avutometinib in combination with defactinib can deliver high response rates for patients with recurrent LGSOC with a promising safety profile to date,” said Susana Banerjee, global and lead investigator of the study and consultant medical oncologist at The Royal Marsden NHS Foundation Trust and Team Leader in Women’s Cancers at The Institute of Cancer Research of London. “It is particularly encouraging to see extensive tumor shrinkage in women who have had several treatment lines, including prior MEK inhibitors. These latest findings suggest the combination may offer a new treatment option for women with this hard-to-treat cancer, and we are hopeful it will become the new standard of care.”

The Company plans to include mature data from RAMP 201, the Verastem sponsored clinical trial, and the investigator-sponsored FRAME study to support filing for accelerated approval. The Company is finalizing the design of a randomized confirmatory trial with the FDA, which is planned to begin in the second half of 2023.

Photo: Susana Banerjee, global and lead investigator of the study and consultant medical oncologist at The Royal Marsden NHS Foundation Trust and Team Leader in Women’s Cancers at The Institute of Cancer Research of London