Verastem Oncology’s pancreatic cancer combination has shown an 86% overall survival (OS) rate in a Phase Ib/IIa trial.
In the RAMP 205 study (NCT05669482), 29 patients were enrolled into the recommended Phase II dose cohort, which evaluated Avmapki Fakzynja (avutometinib plus defactinib) in combination with gemcitabine and nab-paclitaxel in first-line metastatic pancreatic ductal adenocarcinoma (PDAC).
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In the Phase Ib/IIa study, patients were treated with avutometinib 2.4mg twice weekly, defactinib 200 mg twice daily for three weeks on and one week off, and gemcitabine (800 mg/m2) plus nab-paclitaxel (125 mg/m2) administered on days one, eight and 15 of each 28-day cycle. At diagnosis, 90% of patients presented with metastatic disease.
As of the 5 June 2026 data cutoff, with a median follow-up of 9.8 months, the combination demonstrated encouraging clinical activity, including an 86% OS rate at six months, with this data continuing to mature. The progression-free survival (PFS) rate at the same six-month time point was 68%, and the confirmed objective response rate (ORR) was 52%.
The majority (83%) of patients experienced tumour shrinkage. Nine patients remain on treatment at the recommended Phase II dose. Adverse events (AEs) remained generally consistent with the previously reported safety and tolerability profile, with no new safety signals observed.
Dr John Hayslip, CMO of Verastem Oncology, said: “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 Avmapki Fakzynja is 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 signalling and mechanisms of treatment resistance.”
The RAMP 205 trial was designed to evaluate whether simultaneous inhibition of KRAS-driven signalling and FAK-mediated resistance pathways, in combination with standard-of-care chemotherapy, could improve outcomes for patients living with metastatic pancreatic cancer. KRAS is mutated in more than 90% of pancreatic cancers, making it a key driver of tumour growth.
Pancreatic cancer is the third leading cause of cancer-related death in the US and the seventh leading cause of cancer-associated mortality worldwide. Metastatic pancreatic cancer, or stage IV disease, occurs when the cancer spreads beyond the pancreas to distant organs.
Pharma’s giant step in pancreatic cancer drug development
Pancreatic cancer has historically been difficult to treat. This, however, could be nearing an end. Data presented at the American Society of Clinical Oncology (ASCO) meeting 2026 showed that Revolution Medicine’s oral RAS(ON) inhibitor, daraxonrasib, achieved a median OS rate of 13.2 months, almost double that of chemotherapy (6.7 months).
In Revolution’s Phase III RASolute 302, which was presented at the ASCO plenary session, investigators also touted that the survival benefit was matched by a meaningful improvement in progression-free survival (PFS) of 7.2 months vs 3.6 months. Response rates nearly tripled with an objective response rate (ORR) of 31.6% compared to 11.2% in the chemotherapy arm. The field is ecstatic about the prospect of a targeted therapy meaningfully extending OS at a rate that is higher than many frontline chemotherapy regimens achieve.
In conversation with Clinical Trials Arena, Jess Paulus, real-world data (RWD) and pharmacoepidemiologist leader at Ontada, who attended ASCO 2026, said: “The readout from the Phase III pancreatic trial is a once-in-a-lifetime kind of experience. It has been nearly 30 years of research from first discovery to where that trial is right now. That kind of readout doesn’t happen every ASCO.”
While Dr Deborah Patt, executive VP of policy and strategy for Texas Oncology, added: “I have been an oncologist for 20 years, and we’ve really not had such groundbreaking changes in pancreatic cancer. We need to continue to improve, but it is the first real breakthrough in 20 years. I’m incredibly excited about it.”
GlobalData anticipates sales for daraxonrasib to surpass $1bn by 2029, reaching $4.3bn by 2032.
GlobalData is the parent company of Clinical Trials Arena.
