Verastem Oncology's Avmapki Fakzynja (avutometinib + defactinib) combined with gemcitabine/nab‑paclitaxel produced an 86% six‑month overall survival rate in the Phase Ib/IIa RAMP 205 trial (29 patients; median follow‑up 9.8 months). The regimen also showed a six‑month PFS of 68% and a confirmed ORR of 52%, with tumour shrinkage in 83% of participants and no new safety signals. Results are preliminary and will need confirmation in larger trials as data continue to mature.
Verastem’s Avmapki Fakzynja Combo Shows 86% Six‑Month OS in Early Pancreatic Cancer Trial
Pancreatic cancer has seen very few significant advances for some time
Verastem Oncology reported encouraging early results from the Phase Ib/IIa RAMP 205 trial (NCT05669482), where the investigational combination Avmapki Fakzynja (avutometinib plus defactinib) administered with gemcitabine and nab‑paclitaxel produced an 86% overall survival (OS) rate at six months in patients with first‑line metastatic pancreatic ductal adenocarcinoma (PDAC).
In the recommended Phase II dose cohort, 29 patients were treated with avutometinib 2.4 mg twice weekly and defactinib 200 mg twice daily on a three‑weeks‑on, one‑week‑off schedule. Standard chemotherapy was given as gemcitabine 800 mg/m2 plus nab‑paclitaxel 125 mg/m2 on days 1, 8 and 15 of each 28‑day cycle. At diagnosis, 90% of participants presented with metastatic disease.
With a data cutoff of 5 June 2026 and a median follow‑up of 9.8 months, the regimen demonstrated notable activity: a six‑month OS rate of 86%, a six‑month PFS rate of 68%, and a confirmed objective response rate (ORR) of 52%. Tumour shrinkage was observed in 83% of patients, and nine individuals remain on treatment at the recommended Phase II dose.
Adverse events (AEs) were reported as consistent with the known safety and tolerability profile for the agents used; no new safety signals emerged in this analysis.
Trial Rationale and Expert Commentary
The RAMP 205 study tests whether simultaneous inhibition of KRAS‑driven signalling and focal adhesion kinase (FAK)‑mediated resistance pathways, combined with standard‑of‑care chemotherapy, can improve outcomes in metastatic PDAC. KRAS mutations are present in over 90% of pancreatic cancers and are a key oncogenic driver.
Dr John Hayslip, Chief Medical Officer at Verastem Oncology, said the updated data provide important clinical insight into the potential of combined RAF/MEK and FAK inhibition. He noted the combination appears combinable with standard chemotherapy and may help overcome resistance mechanisms inherent to pancreatic cancer, supporting further clinical evaluation.
Context: Targeted RAS Agents and the Changing Landscape
These results arrive as the pancreatic cancer field sees renewed optimism following results presented at ASCO 2026 for Revolution Medicine’s oral RAS(ON) inhibitor, daraxonrasib. In the randomized Phase III RASolute 302 trial, daraxonrasib extended median OS to 13.2 months versus 6.7 months with chemotherapy, improved median PFS (7.2 vs 3.6 months), and raised ORR to 31.6% versus 11.2% for chemotherapy.
Physicians quoted at ASCO described the daraxonrasib readout as a major milestone after decades of research. Market analysts at GlobalData project daraxonrasib sales could exceed $1 billion by 2029 and reach $4.3 billion by 2032.
Limitations and Next Steps
These RAMP 205 data are early and based on a small cohort (29 patients) with a median follow‑up under 10 months. Results are maturing and require confirmation in larger, controlled trials. Verastem plans further evaluation in subsequent studies to validate durability, safety and whether the combination meaningfully improves long‑term outcomes compared with current standards of care.
Note: This article is based on data reported by Verastem Oncology and contextual information presented at ASCO 2026. The original piece was published by Clinical Trials Arena, a GlobalData brand.
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