BOSTON — Verastem Oncology announced new clinical trial analyses showing promising results for its combination therapy of avutometinib and defactinib in patients with recurrent low-grade serous ovarian cancer (LGSOC), including those whose tumors do not carry KRAS mutations.
The findings from the Phase 2 RAMP 201 trial and an external control arm analysis are being presented at the International Gynecologic Cancer Society (IGCS) 2026 Annual Global Meeting in Montréal, Canada, October 1-3.
Molecular profiling of tumor samples from RAMP 201 showed that the combination therapy demonstrated activity across several molecular subgroups of patients with KRAS wild-type disease.
Among patients whose tumors lacked KRAS, NRAS and BRAF mutations, the treatment achieved a confirmed objective response rate of 18% and median progression-free survival of 13 months. Patients with KRAS wild-type tumors carrying NRAS or BRAF mutations had a confirmed response rate of 22%.
“Patients whose tumors are wild-type for KRAS, NRAS, and/or BRAF have typically experienced response rates under 10% with trametinib, chemotherapy or endocrine therapy,” said Professor Susana Banerjee, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Team Leader in Women’s Cancers at The Institute of Cancer Research, London.
“This analysis provides additional insight into molecular biology of recurrent LGSOC and suggests that targeting RAF, MEK, and FAK with avutometinib plus defactinib may provide clinically meaningful benefit beyond tumors driven by KRAS, NRAS or BRAF mutations,” she added.
A separate external control arm analysis compared outcomes from RAMP 201 with those of patients receiving conventional chemotherapy or anti-estrogen therapy in the GOG 281 trial.
Among patients with KRAS-mutated disease, the combination achieved a weighted objective response rate of 38.7%, compared with 0% for conventional care. Median weighted progression-free survival was 22.1 months, compared with 6.5 months.
For patients with KRAS wild-type disease, weighted response rates were 22.7% with the combination versus 7.9% with conventional care. Median weighted progression-free survival was 11.3 months versus 7.7 months, respectively.
Verastem said the analysis demonstrated statistically significant improvements in progression-free survival in both groups. However, the comparison relied on an external control group rather than a direct randomized comparison between the two treatments.
Michael Kauffman, M.D., Ph.D., President of Development at Verastem Oncology, said the findings provide additional evidence of the combination’s potential in treating recurrent LGSOC, including patients whose tumors lack KRAS mutations.
The company is also presenting previously reported results from its Phase 2 RAMP 201J study involving Japanese patients.
Among 16 evaluable patients, the combination achieved an overall response rate of 44% and a disease control rate of 94%. Response rates were 71% among patients with KRAS-mutated tumors and 22% among those with KRAS wild-type tumors.
At the study’s May 29 data cutoff, 11 of the 16 patients remained on treatment.
The findings support further investigation of the combination in a broader population of patients with recurrent LGSOC. Avutometinib plus defactinib is already approved for patients with KRAS-mutated recurrent disease.
LGSOC is a rare form of ovarian cancer that frequently recurs and is generally less responsive to conventional chemotherapy than high-grade serous ovarian cancer. Approximately 6,000 to 8,000 women in the United States and 80,000 worldwide are living with the disease.
