Pancreatic cancer trial nearly doubles median survival with daraxonrasib

Oncologists do not usually interrupt a scientific lecture with a standing ovation. That is what happened at a conference in Chicago in late May, when the results of a phase 3 trial of a drug called daraxonrasib were presented: in patients with previously treated metastatic pancreatic cancer, median survival almost doubled, from 6.7 months on standard chemotherapy to 13.2 months on the new drug.

What the trial found

The study, called RASolute 302, enrolled about 500 patients whose metastatic pancreatic ductal adenocarcinoma had progressed after first-line treatment. They were randomly assigned either to oral daraxonrasib or to the physician's choice of standard second-line chemotherapy. Alongside the gain in median survival, the risk of death fell by roughly 60%, and patients on the drug lived about twice as long before their disease progressed.

Daraxonrasib is an oral, multi-selective inhibitor that targets RAS proteins in their active, or "ON", state. Instead of blocking a single mutant variant, it is designed to suppress several active forms of RAS at the same time.

Why RAS matters

RAS is among the most frequently mutated gene families in human cancer, and more than 90% of pancreatic tumours carry an activating RAS mutation, most often at codon G12. For decades these proteins were treated as practically undruggable: they are small and smooth, with no obvious pocket where a conventional molecule could bind. Pancreatic cancer has been especially resistant to new treatments, and second-line options have historically offered a median survival of only a few months.

A master switch

Because RAS sits near the top of several growth-signalling pathways, a drug that can switch it off may prove useful well beyond a single tumour type — the reason some researchers describe RAS as cancer's master switch. The Chicago results remain early: longer follow-up will show how durable the benefit is, and the data have not yet been reviewed by regulators. But for a disease that has seen so little progress for so long, the survival curve shown to that audience was a rare sight.