Revolution goes adjuvant

Revolution Medicines is expanding the pivotal push with its pan-RAS inhibitor daraxonrasib, with details of an adjuvant pancreatic cancer study recently appearing on clinicaltrials.gov.

The Rasolute-304 trial, set to start in December, has been in the works for some time, but now there are details on its design. The study will enrol patients with resected pancreatic ductal adenocarcinoma (PDAC) who have completed neoadjuvant and/or adjuvant chemotherapy, who will then either receive daraxonrasib or undergo observation. The primary endpoint is disease-free survival, with overall survival a key secondary endpoint.

According to Revolution, resectable disease accounts for 15-25% of newly diagnosed US pancreatic cancer patients; surgery with perioperative chemotherapy offers the possibility of a cure, but around 80% advance to metastatic disease, the group added.

First-line plans 

Meanwhile, there’s no clinicaltrials.gov listing yet for a first-line PDAC trial of daraxonrasib, known as Rasolute-303. Revolution unveiled the design of this study earlier this year, adding that it would start in the second half of 2025. The group reiterated this plan during its third-quarter earnings call in November, but with December now under way time is running out.

Here, one question is whether daraxonrasib monotherapy or a chemo combo will ultimately prevail: efficacy has looked better with the combo, but with an increase in toxicity. Rasolute-303 is set to test both regimens.

The big upcoming event for daraxonrasib will be data from Rasolute-302 in second-line PDAC, due next year. Notably, this trial is evaluating patients with and without RAS mutations, something Revolution has said will also be the case for the front-line Rasolute-303.

The adjuvant Rasolute-304 trial, meanwhile, appears to be taking a similar approach, only asking that patients have documented RAS mutation status. Around 90% of PDAC patients carry a RAS driver mutation, Revolution has estimated.

In lung cancer, however, Revolution is aiming squarely at RAS mutations, which are implicated in around 30% of cases. Here, the second-line Rasolve-301 trial started this year, and the company also has pivotal plans in first-line disease.

So far Revolution hasn’t released many details, but it has said the front-line trial will start in 2026, and will test daraxonrasib plus Keytruda and chemo. Revolution cites an 86% ORR with daraxonrasib plus Keytruda in patients with PD-L1 expression of 50% or greater, and 60% with daraxonrasib plus Keytruda and chemo in <50% expressers, although patient numbers are small.

Phase 3 trials of daraxonrasib

Source: OncologyPipeline & clinicaltrials.gov.