BOSTON, June 17, 2026
Verastem Oncology announced positive updated safety and efficacy findings from the Phase 1b/2a RAMP 205 clinical trial, evaluating avutometinib plus defactinib in combination with gemcitabine and nab-paclitaxel as a first-line treatment for metastatic pancreatic ductal adenocarcinoma (PDAC). The updated analysis from the Recommended Phase 2 Dose (RP2D) cohort included 29 patients, with 90% presenting with Stage IV metastatic disease at diagnosis. At a median follow-up of 9.8 months, the investigational combination achieved an 86% overall survival rate at six months, while 68% of patients remained progression-free at six months. The study also reported a confirmed objective response rate of 52%, with 83% of patients experiencing measurable tumor shrinkage, highlighting the potential of combining RAF/MEK inhibition, FAK inhibition, and standard chemotherapy to improve outcomes in one of the deadliest forms of cancer.
Targeting KRAS-Driven Resistance Pathways
The RAMP 205 trial was designed to address the biological complexity of pancreatic cancer, where more than 90% of tumors harbor KRAS mutations, making KRAS signaling a major driver of tumor growth and treatment resistance. Avutometinib inhibits both RAF and MEK signaling, while defactinib blocks FAK, a pathway frequently activated when RAF/MEK signaling is inhibited and a known contributor to therapeutic resistance. Combined with the standard chemotherapy regimen of gemcitabine and nab-paclitaxel, this multi-targeted strategy aims to deliver a more comprehensive blockade of cancer cell survival pathways. Importantly, the updated analysis showed no new safety signals, with the safety profile remaining consistent with previously reported findings. Nine patients remain on active treatment, while overall survival data continue to mature, providing additional opportunities to evaluate long-term clinical benefit.
PanCAN Collaboration Supports Innovative Development
The RAMP 205 program is supported by the Pancreatic Cancer Action Network (PanCAN) through its Therapeutic Accelerator Award, which awarded $3.8 million to Verastem Oncology in 2022 to accelerate the development of innovative treatment strategies for metastatic pancreatic cancer. Alongside financial support, PanCAN established a collaborative scientific working group with leading academic experts to better understand the biology of the investigational combination. According to the company, the encouraging clinical activity observed in RAMP 205 reinforces continued exploration of RAF/MEK and FAK pathway inhibition as a strategy to overcome treatment resistance in pancreatic cancer. Verastem also indicated that future development plans will be guided by the final overall survival analysis and supported by additional research involving its oral KRAS G12D inhibitor VS-7375, which is currently advancing across multiple registration-directed clinical studies targeting KRAS G12D-mutated cancers.
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Advancing Precision Oncology for Pancreatic Cancer
Pancreatic cancer remains one of the most aggressive and difficult-to-treat malignancies, with metastatic disease carrying a five-year survival rate of approximately 3%. Despite advances in chemotherapy, treatment options remain limited, particularly for patients whose tumors are driven by KRAS mutations. By combining targeted inhibition of RAF, MEK, and FAK with established chemotherapy, Verastem Oncology aims to improve both tumor response and long-term survival while addressing mechanisms that frequently lead to drug resistance. The company plans to continue evaluating this therapeutic approach through ongoing clinical development and potential strategic collaborations. The positive RAMP 205 results further strengthen Verastem’s broader oncology pipeline focused on RAS/MAPK pathway-driven cancers, supporting continued investment in precision medicine approaches designed to improve outcomes for patients with advanced pancreatic cancer.
Source:Verastem Oncology press release
