{"entity":{"id":"rasolute-302","kind":"trial","name":"RASolute 302","aka":[],"tldr":"The trial that nearly doubled survival in previously treated pancreatic cancer, presented in the ASCO 2026 plenary. The biggest result in the disease's history.","summary":"500 patients, 59 sites. Topline 13 April 2026; presented by Brian Wolpin (Dana-Farber) at the ASCO 2026 plenary (31 May) with simultaneous NEJM publication. Median OS 13.2 vs 6.7 months (HR 0.40, p<0.0001); PFS also significantly improved. The NDA (220910) was received by the FDA on 17 July 2026 and approved on 26 August 2026 as Rasonque for metastatic pancreatic adenocarcinoma after at least one prior systemic therapy. First-line (RASolute 303) and adjuvant (RASolute 304) trials follow.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT06625320","url":"https://clinicaltrials.gov/study/NCT06625320"},{"label":"FDA approval notice (26 Aug 2026)","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daraxonrasib-metastatic-pancreatic-adenocarcinoma"},{"label":"Revolution Medicines announcement","url":"https://ir.revmed.com/news-releases/news-release-details/daraxonrasib-demonstrates-unprecedented-overall-survival-benefit"},{"label":"JCO abstract LBA5","url":"https://ascopubs.org/doi/10.1200/JCO.2026.44.17_suppl.LBA5"},{"label":"O'Reilly et al., RASolute 302 (NEJM 2026)","url":"https://doi.org/10.1056/NEJMoa2605555"},{"label":"Rasonque label (openFDA): RASolute 302 efficacy table and adverse reactions","url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22RASONQUE%22"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":["kras-inhibitors"],"targets":["kras"],"drugs":["daraxonrasib"],"companies":["revolution-medicines"],"institutions":["dana-farber"],"pathways":[],"terms":[],"trials":["nct07491445","nct07252232","codebreak-100","napoli-1","conko-003"],"people":[],"bottlenecks":[],"keyPapers":["paper-bournet-kras-g12d-prognosis-pancreatic-ctg-2016"],"journals":[],"dependsOn":[],"notes":["Primary paper (NEJM 2026) and label: 500 patients, 91.8 percent with RAS G12 mutations, randomised 1 to 1 to daraxonrasib 300 mg daily or investigator's choice chemotherapy after one prior line; dual primary endpoints in the RAS G12 population were overall survival 13.2 against 6.6 months and progression-free survival 7.3 against 3.5 months (hazard ratios 0.40 and 0.45); in the overall population 13.2 against 6.7 months (hazard ratio 0.40) and 7.2 against 3.6 months (hazard ratio 0.49; label 95 percent confidence interval 0.38 to 0.64), response 30 against 11 percent. Grade 3 or higher adverse events 61.8 against 69.6 percent; treatment-related discontinuation 1.2 against 11.2 percent. Registry: sites in the United States, France, Germany, Italy, Japan, Puerto Rico and Spain, none in the UK; primary completion June 2026. Label (effective 27 August 2026): indicated after at least one prior systemic therapy or for adults not candidates for multi-agent chemotherapy; dose interruptions in 69 percent (rash 27, stomatitis 20 percent)."],"nct":"NCT06625320","phase":"3","setting":"Metastatic PDAC after one prior line of chemotherapy: daraxonrasib vs investigator's choice chemotherapy","sponsor":"Revolution Medicines","result":"OS 13.2 vs 6.7 months, HR 0.40.","started":"2024-10-16","startedType":"actual","yearReported":2026,"enrolled":500,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Daraxonrasib","value":13.2},{"name":"Chemotherapy (gemcitabine/nab-paclitaxel or mFOLFOX6)","value":6.7}],"hr":0.4,"source":"https://clinicaltrials.gov/study/NCT06625320"},{"endpoint":"Progression-free survival by blinded independent central review (overall population)","unit":"months","arms":[{"name":"Daraxonrasib","n":248,"value":7.2,"note":"95% CI 5.7 to 7.5"},{"name":"Chemotherapy (mFOLFIRINOX, gemcitabine/nab-paclitaxel, FOLFOX or liposomal irinotecan with 5-FU/LV)","n":252,"value":3.6,"note":"95% CI 2.9 to 4.2"}],"hr":0.49,"ci":[0.38,0.64],"p":"<0.0001","source":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22RASONQUE%22"},{"endpoint":"Objective response rate by blinded independent central review (overall population)","unit":"%","arms":[{"name":"Daraxonrasib","n":248,"value":30,"note":"95% CI 25 to 36"},{"name":"Chemotherapy","n":252,"value":11,"note":"95% CI 7 to 15"}],"p":"<0.0001","source":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22RASONQUE%22"}],"replication":"Single pivotal trial reported 2026; consistent with the phase 1/2 signal (median OS ~14.5 months in second line). First-line RASolute 303 ongoing."},"route":"/trials/rasolute-302/","neighbours":{"cancer":[{"id":"kras-g12c-pdac","kind":"cancer","name":"KRAS G12C-mutant pancreatic ductal adenocarcinoma","route":"/cancers/kras-g12c-pdac/"},{"id":"locally-advanced-pdac","kind":"cancer","name":"Locally advanced unresectable pancreatic ductal adenocarcinoma","route":"/cancers/locally-advanced-pdac/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"kras-inhibitors","kind":"technology","name":"KRAS & RAS inhibitors","route":"/technologies/kras-inhibitors/"}],"target":[{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"}],"drug":[{"id":"daraxonrasib","kind":"drug","name":"Daraxonrasib","route":"/drugs/daraxonrasib/"},{"id":"liposomal-irinotecan","kind":"drug","name":"Liposomal irinotecan","route":"/drugs/liposomal-irinotecan/"},{"id":"nalirifox","kind":"drug","name":"NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)","route":"/drugs/nalirifox/"}],"company":[{"id":"revolution-medicines","kind":"company","name":"Revolution Medicines","route":"/companies/revolution-medicines/"}],"institution":[{"id":"dana-farber","kind":"institution","name":"Dana-Farber Brigham Cancer Center","route":"/institutions/dana-farber/"}],"trial":[{"id":"codebreak-100","kind":"trial","name":"CodeBreaK 100 (pancreatic cancer cohort)","route":"/trials/codebreak-100/"},{"id":"conko-003","kind":"trial","name":"CONKO-003 (OFF)","route":"/trials/conko-003/"},{"id":"napoli-1","kind":"trial","name":"NAPOLI-1","route":"/trials/napoli-1/"},{"id":"nct07252232","kind":"trial","name":"Study of Daraxonrasib (RMC-6236) in Patients With Resected Pancreatic Ductal Adenocarcinoma (PDAC)","route":"/trials/nct07252232/"},{"id":"nct07491445","kind":"trial","name":"Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma","route":"/trials/nct07491445/"}],"paper":[{"id":"paper-holderfield-ras-on-multi-selective-inhibitor-nature-2024","kind":"paper","name":"Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy","route":"/key-papers/paper-holderfield-ras-on-multi-selective-inhibitor-nature-2024/"},{"id":"paper-daraxonrasib-pancreatic-n-engl-j-med-2026","kind":"paper","name":"Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer","route":"/key-papers/paper-daraxonrasib-pancreatic-n-engl-j-med-2026/"},{"id":"paper-bournet-kras-g12d-prognosis-pancreatic-ctg-2016","kind":"paper","name":"KRAS G12D mutation subtype is a prognostic factor for advanced pancreatic adenocarcinoma","route":"/key-papers/paper-bournet-kras-g12d-prognosis-pancreatic-ctg-2016/"}],"idea":[{"id":"idea-bio1-pan-ras-covalent-g12d","kind":"idea","name":"Covalent chemistry for the RAS mutations that still have no drug","route":"/ideas/idea-bio1-pan-ras-covalent-g12d/"},{"id":"idea-shared-kras-vaccine-adjuvant","kind":"idea","name":"Off-the-shelf KRAS vaccines after pancreatic cancer surgery","route":"/ideas/idea-shared-kras-vaccine-adjuvant/"},{"id":"idea-pdac-ras-inhibitor-combinations-and-sequencing","kind":"idea","name":"RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression","route":"/ideas/idea-pdac-ras-inhibitor-combinations-and-sequencing/"},{"id":"idea-ras-inhibitor-neoadjuvant-pdac","kind":"idea","name":"RAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable","route":"/ideas/idea-ras-inhibitor-neoadjuvant-pdac/"}],"roadmap":[{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"},{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}],"bottleneck":[{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}]}}