S19 Ep20: ESMO 2026 Data Continue to Shine a Spotlight on Daraxonrasib’s Activity in Pretreated Metastatic Pancreatic Cancer

In today's episode, we spoke with Zev A. Wainberg, MD, MSc, about subgroup data from the phase 3 RASolute 302 trial (NCT06625320) of daraxonrasib (Rasonque) in patients with previously treated metastatic pancreatic cancer, which were presented at the 2026 ESMO Congress. Dr Wainberg is a professor of medicine at the David Geffen School of Medicine at UCLA and co-director of the UCLA GI Oncology Program in Los Angeles, California.

In our exclusive interview, Dr Wainberg discussed how daraxonrasib improved overall survival (OS) vs investigator’s choice of standard-of-care chemotherapy across RAS genotype subgroups, preselected chemotherapy regimens, and prior treatment settings. Additionally, Dr Wainberg shared practical advice for managing rash and stomatitis, including treatment holds and dose reductions. Finally, Dr Wainberg explained how RAS(ON) inhibition is moving into earlier lines of therapy and why he supports genomic testing at diagnosis.

Dr Wainberg presented the analyses at the 2026 ESMO Congress on behalf of the RASolute 302 investigators. The trial randomly assigned 500 patients with metastatic pancreatic adenocarcinoma who had received 1 prior fluoropyrimidine- or gemcitabine-based regimen in the metastatic setting to daraxonrasib at 300 mg once daily (n = 248) or investigator’s choice of chemotherapy (n = 252). In the primary analysis, daraxonrasib generated a median OS of 13.2 months (95% CI, 10.0-not estimable) vs 6.7 months (95% CI, 5.8-8.0) with chemotherapy (HR, 0.40; 95% CI, 0.30-0.53; P = 4.6 × 10–11).

Dr Wainberg first addressed the subgroup findings by RAS genotype. RAS G12D and G12V mutations predominated, accounting for 43.2% and 35.6% of the study population, respectively, and Dr Wainberg noted that nearly every genotype subgroup favored daraxonrasib for OS. The OS HRs were 0.49 (95% CI, 0.33-0.74) in the G12D subgroup (n = 95 vs 121), 0.32 (95% CI, 0.19-0.54) in the G12V subgroup (n = 102 vs 76), 0.61 (95% CI, 0.29-1.30) in the G12R subgroup (n = 30 vs 31), and 0.43 (95% CI, 0.09-1.98) in patients with no RAS mutation identified (n = 9 vs 7). 

Turning to sequencing, Dr Wainberg explained that neither the first-line regimen nor the chemotherapy selected for the control arm appeared to change the benefit of daraxonrasib. The OS HR was 0.45 (95% CI, 0.32-0.65) when gemcitabine plus nab-paclitaxel (Abraxane) was the preselected comparator (n = 140 vs 141), 0.46 (95% CI, 0.23-0.95) for pooled modified FOLFIRINOX or FOLFOX (n = 30 vs 30), and 0.32 (95% CI, 0.18-0.58) for nanoliposomal irinotecan (Onivyde) plus 5-fluorouracil and leucovorin (n = 78 vs 81).

Looking ahead, Dr Wainberg noted that trials of RAS(ON) inhibition are already enrolling in the adjuvant and first-line settings, and that many KRAS inhibitors presented at the meeting are moving quickly to phase 3 studies.