Revolution's first-line bet starts recruiting

Having long promised to take its pan-RAS inhibitor daraxonrasib into first-line pancreatic cancer, Revolution has finally posted a pivotal study in this setting, Rasolute-303, on clinicaltrials.gov. This was expected to begin in 2025, and appears to have started enrolment this month. It will assess both daraxonrasib monotherapy and its combination with chemotherapy. The company chose to pair daraxonrasib with gemcitabine plus Abraxane rather than with folfirinox; the latter combination yielded higher response rates, but was accompanied by greater toxicity. Revolution also highlighted the need for relatively fit patients as a potential limitation for that regimen, but Rasolute-303 will enrol such patients (ECOG status 0 or 1) anyway, so this might not have been a significant factor. Additional daraxonrasib data in pancreatic cancer are to be presented in a late-breaking session at AACR. Earlier results indicated a 55% response rate in 31 evaluable patients treated with the combo. However, toxicity remains a problem, as these earlier results also revealed 58% rate of grade 3 or higher adverse events. Meanwhile, by the mid-year the company expects data from the pivotal second-line Rasolute-302 trial, following promising signals seen in early uncontrolled studies. Revolution has also initiated a trial in the adjuvant pancreatic setting. Phase 3 trials of daraxonrasibTrialSettingRegimenPrimary endpointNotRasolute-3022nd-line PDAC (RASm & RASwt)Daraxonrasib (300mg), vs investigator’s choice chemoPFS & OS in G12Xm ptsData due H1 2026Rasolute-3031st-line PDAC (RASm & RASwt)Daraxonrasib monotx (300mg) or daraxonrasib (200mg) + GnP chemo, vs GnP chemoPFS & OSStarted Mar 2026Rasolute-304Adjuvant PDACDaraxonrasib (300mg), vs observationDFSStarted Dec 2025Rasolve-3012nd-line NSCLC (RASm)Daraxonrasib (200mg), vs docetaxelPFS & OSStarted May 2025Unnamed1st-line NSCLC (RASm)Daraxonrasib + Keytruda + chemoNot disclosedTo start 2026Source: OncologyPipeline & clinicaltrials.gov.