Verastem announces positive Phase 1/2 safety and efficacy results in PDAC

Verastem (VSTM) announced positive updated safety and efficacy results from the RAMP 205 Phase 1/2 trial evaluating avutometinib plus defactinib in combination with gemcitabine and Nab-paclitaxel in the front-line for patients with metastatic pancreatic ductal adenocarcinoma, or PDAC. As of April 25, 2025, patients in the dose level 1 cohort, which was selected as the recommended Phase 2 dose, achieved an overall response rate of 83% – 10/12 -. As of April 25, 60 patients had been treated in one of five dose regimens with the combination of avutometinib and defactinib with gemcitabine and Nab-paclitaxel in frontline metastatic PDAC. In the dose level 1 cohort, 12 patients received 2.4 mg of avutometinib twice a week, 200 mg of defactinib twice a day for 3 weeks out of every 4 and 800 mg/m2 of gemcitabine and 125 mg/m2 of Nab-paclitaxel on a schedule of day 1, day 8 and day 15. In dose level 1, 83% of patients achieved partial responses.The company has selected dose level 1 as the RP2D, has met the pre-defined criteria to advance beyond the first stage of the expansion study, and is now enrolling up to 29 patients at this dose level. In evaluating all the dose cohorts, dose level 1 demonstrated the highest response rate and across all five dose cohorts, 92% of efficacy evaluable patients showed tumor reduction as best response. No new safety signals have emerged. While anticipating results from the study expansion cohort, the company is now developing plans for a registrational Phase 3 front-line metastatic PDAC trial to begin in 2026.