#ASCO26# This one is special. This is the hottest paper of 2026 and potentially in the history of pancreatic cancer. Let’s dive in. RASolute 302: Daraxonrasib vs investigator’s choice chemotherapy in previously treated metastatic pancreatic cancer Abstract LBA5 (soon!) Presentation: May 31, 2026, 3:21-3:33 PM CDT For decades, pancreatic cancer has been where good ideas go to die. We have optimized chemotherapy. We have sequenced chemotherapy. We have celebrated modest gains. But the central driver of PDAC has always been sitting there in plain sight: RAS. More than 90% of pancreatic cancers have oncogenic RAS mutations, and until recently, we had essentially nothing direct to do about it. Daraxonrasib is an oral RAS(ON) multiselective inhibitor targeting the active GTP-bound state of mutant and wild-type RAS. And in RASolute 302, it delivered. Quick hits: 📌 Phase 3 international randomized trial 500 patients with previously treated mPDAC Daraxonrasib vs investigator’s choice chemotherapy 🧬 RAS G12 population 91.8% of patients had RAS G12 mutations 📈 OS in RAS G12 population 13.2 vs 6.6 months HR 0.40 P<0.001 📈 OS in overall population 13.2 vs 6.7 months HR 0.40 P<0.001 📊 PFS in RAS G12 population 7.3 vs 3.5 months HR 0.45 P<0.001 📊 PFS in overall population 7.2 vs 3.6 months HR 0.49 P<0.001 🔥 12-month OS Overall population: 53.2% vs 17.3% ⚠️ Toxicity matters, but this was not just more efficacy for more toxicity Grade ≥3 AEs: 61.8% vs 69.6% TRAEs leading to discontinuation: 1.2% vs 11.2% This is the kind of survival curve we almost never get to see in pancreatic cancer. This validates RAS(ON) inhibition in the most RAS-addicted major cancer. It takes a target we have talked about for decades and turns it into a clinically meaningful survival benefit in a randomized phase 3 trial. The next questions come fast: 1L combinations, maintenance, perioperative disease, sequencing, resistance, toxicity management, and whether this becomes a new backbone. RAS is here, and it couldn’t have come sooner. @TheGutonclab @UGrewalMD @TimothyJBrownMD @OncoAlert @Onco_Nexus @ASCO @NazliDizman @LauraAlderMD @DVAraujoMD @DrBarbiOnc @LauraEsfeller @FunchainMD @YGaritaonaindia @DrSAHaddad @jgong15 @iandresmeraz @SakditadMD @RamilaShilpakar @RohitBanwar @lungoncdoc