10/25/2026  |  Abigail Beaney  |  Clinical Trials Arena

https://www.clinicaltrialsarena.com/news/esmo26-clinical-progress-shifts-a-historically-difficult-pancreatic-cancer-landscape/ 

Revolution Medicines’ impressive daraxonrasib data has spurred hope in the pancreatic cancer space.

Pancreatic cancer has historically presented a poor clinical outlook, offering patients few effective therapeutic options. Because the disease rarely causes early symptoms, diagnoses typically occur at advanced stages, where a dense, fibrous stroma surrounds tumours and shields them from systemic treatment.

Against this backdrop, data from Revolution Medicines Phase III RASolute 302 trial (NCT06625320) showed a near doubling of overall survival (OS) in patients treated with the daily oral RAS(ON) inhibitor Rasonque (daraxonrasib). The US Food and Drug Administration (FDA) approved the drug in August 2026.

The data showed a median overall survival (OS) of 13.2 months in the investigational arm, compared with 6.7 months in the standard-of-care (SOC) arm.

Although a substantial amount of data has already been released, Revolution presented further findings at the 2026 European Society for Medical Oncology (ESMO) Congress.

Trial investigator Dr Zev Wainberg, a professor of medicine and gastrointestinal medical oncology at UCLA, presented a subgroup analysis stratified by tumour mutational status. For the most common mutation, RAS G12D, which accounted for 43.2% of patients in the study, the overall response rate (ORR) was 32%, compared to 11% in the placebo cohort. In RAS G12V, ORR was 24% compared to 9% in the placebo cohort. OS throughout all of the mutation subgroups favoured Rasonque.

Tango Therapeutics combo improves PFS
Also making headlines at ESMO 2026 is Tango Therapeutics, which previewed its Phase I/II study of vopimetostat, an investigational PRMT5 inhibitor with first- and best-in-class potential, in combination with Revolution Medicines’ Rasonque in patients with MTAP-deleted and RAS-mutant metastatic pancreatic ductal adenocarcinoma.

As of the data cutoff date of 20 August 20, 2026, the study demonstrated an 82% ORR, with median PFS having not yet been reached. The cutoff saw a nine-month PFS rate of 88% in 22 patients with 2L/3L MTAP-deleted/RAS-mutant pancreatic ductal adenocarcinoma who were efficacy-evaluable.

Dr Malte Peters, CEO and president of Tango Therapeutics, said: “It is encouraging to see that the clinical activity and tolerability observed in our initial June 2026 dataset has been confirmed with longer follow-up and in a larger patient population, affirming our belief that the response rate and durability observed with vopimetostat plus Rasonque surpass any published PDAC datasets, even in front-line settings.”

These data prompted Tango to plan a registrational Phase III trial evaluating vopimetostat with Rasonque as a first-line treatment for MTAP-deleted pancreatic cancer, with initiation expected in the first half of 2027.