Boston — Verastem Oncology announced positive updated safety and efficacy results from a Phase 1b/2a cohort of its RAMP 205 study evaluating avutometinib plus defactinib in combination with standard-of-care chemotherapy in first-line metastatic pancreatic ductal adenocarcinoma.
The study evaluated the combination of avutometinib and defactinib with gemcitabine and nab-paclitaxel in 29 patients in the recommended Phase 2 dose cohort. Verastem said 90% of patients in the study had metastatic, or Stage IV, disease at diagnosis.
KRAS is mutated in more than 90% of pancreatic cancers, making it a key driver of tumor growth. The RAMP 205 trial was designed to evaluate whether simultaneously targeting KRAS-driven signaling and FAK-mediated resistance pathways, in combination with standard chemotherapy, could improve outcomes for patients with metastatic pancreatic cancer.
“The updated data from the RAMP 205 trial provide important clinical insights into the potential impact of combined RAF/MEK and FAK inhibition as a therapeutic option for pancreatic cancer. While pancreatic cancer remains one of the most challenging cancers to treat, the early survival trends and deep responses observed in this study indicate that avutometinib and defactinib are combinable with standard-of-care chemotherapy and may help overcome resistance mechanisms inherent in pancreatic cancer and support further exploration of strategies designed to address oncogenic signaling and mechanisms of treatment resistance,” said John Hayslip, M.D., chief medical officer at Verastem Oncology. “We are grateful to PanCAN, the RAMP 205 investigators, and especially the patients and families who participated in the trial.”
As of the June 5, 2026, data cutoff, with a median follow-up of 9.8 months, the combination showed an 86% overall survival rate at six months, with survival data continuing to mature. The six-month progression-free survival rate was 68%, and the confirmed objective response rate was 52%, or 15 of 29 patients.
Verastem said most patients in the recommended Phase 2 dose cohort, 83%, experienced tumor shrinkage. Nine patients remain on treatment at that dose level. The company said adverse events were generally consistent with the previously reported safety and tolerability profile, with no new safety signals observed.
“For patients and their families facing a pancreatic cancer diagnosis, every advance in research and understanding of the underlying biology driving this cancer matters,” said Anna Berkenblit, M.D., chief scientific and medical officer of the Pancreatic Cancer Action Network. “We awarded Verastem the PanCAN Therapeutic Accelerator Award in 2022 to invest in research and development of novel treatment approaches. The results of the RAMP 205 trial underscore the importance of continued research in the RAS/MAPK-pathway to help improve outcomes for patients living with pancreatic cancer.”
The recommended Phase 2 dose included avutometinib 2.4 mg twice weekly, defactinib 200 mg twice daily for three weeks on and one week off, and gemcitabine plus nab-paclitaxel on Days 1, 8 and 15 of each 28-day cycle.
“We will continue to evaluate the potential role of avutometinib plus defactinib in metastatic pancreatic cancer, including future development opportunities and potential strategic collaborations, informed by the final overall survival results from the study as well as emerging data from VS-7375, our investigational potential best-in-class oral KRAS G12D (ON/OFF) inhibitor, currently being evaluated in metastatic pancreatic cancer as both a monotherapy and in combination regimens,” said Dan Paterson, president and chief executive officer of Verastem Oncology. “We will also assess opportunities to share these data in the future, including at a medical meeting.”
In May 2022, Verastem was selected by PanCAN to receive the inaugural PanCAN Therapeutic Accelerator Award, which supported the evaluation of avutometinib in combination with defactinib in front-line metastatic pancreatic cancer. The award provided Verastem with $3.8 million following a competitive review process.
RAMP 205 is a multicenter, open-label, single-arm Phase 1b/2a study evaluating the safety, tolerability and efficacy of avutometinib and defactinib in combination with gemcitabine and nab-paclitaxel in patients with previously untreated metastatic pancreatic ductal adenocarcinoma.
