{"entity":{"id":"zoldonrasib","kind":"drug","name":"Zoldonrasib","aka":[],"tldr":"The first drug aimed specifically at KRAS G12D, the single most common mutation in pancreatic cancer. Early combination data in 2026 showed half of previously treated patients responding.","summary":"Revolution Medicines' covalent tri-complex inhibitor of KRAS G12D(ON). Breakthrough Therapy designation in G12D NSCLC (2025). At ESMO GI 2026, zoldonrasib plus daraxonrasib in previously treated RAS G12D metastatic PDAC (n=60, cutoff 9 Feb 2026): ORR 50% and DCR 97% in second line, median PFS 9.6 months; grade ≥3 treatment-related events 35% (rash, anaemia, stomatitis). First-line combination with gemcitabine/nab-paclitaxel showed high response rates and ctDNA clearance. Phase 3 planning underway.","status":"phase-2","asOf":"2026-09-06","links":[{"label":"Revolution Medicines, ESMO GI 2026","url":"https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-presents-phase-12-clinical-data-zoldonrasib"},{"label":"OncLive report","url":"https://www.onclive.com/view/zoldonrasib-combinations-show-compelling-antitumor-activity-in-ras-g12d-mutant-metastatic-pdac"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac","nsclc","colorectal"],"sections":[],"technologies":["kras-inhibitors"],"targets":["kras"],"drugs":["daraxonrasib"],"companies":["revolution-medicines"],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":["nct07805954","nct07621718","nct07777822","nct06445062","nct07397338","nct06922591"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"RMC-9805","modality":"Small-molecule RAS(ON) G12D-selective inhibitor","mechanism":"Cyclophilin-A-mediated tri-complex that covalently engages the G12D mutant aspartate and blocks effector binding in the active state.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/zoldonrasib/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"kras-g12c-colorectal","kind":"cancer","name":"KRAS G12C-mutant colorectal cancer","route":"/cancers/kras-g12c-colorectal/"},{"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":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"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/"}],"company":[{"id":"revolution-medicines","kind":"company","name":"Revolution Medicines","route":"/companies/revolution-medicines/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"trial":[{"id":"nct07777822","kind":"trial","name":"Study of Pembrolizumab + Pemetrexed + Platinum Chemotherapy With or Without Zoldonrasib as First Line Treatment in Metastatic Non-squamous RAS G12D-Mu","route":"/trials/nct07777822/"},{"id":"nct07397338","kind":"trial","name":"Study of RAS(ON) Inhibitors in Combination With Ivonescimab in Patients With Solid Tumors","route":"/trials/nct07397338/"},{"id":"nct06445062","kind":"trial","name":"Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors","route":"/trials/nct06445062/"},{"id":"nct06040541","kind":"trial","name":"Study of RMC-9805 in Participants With KRAS G12D-Mutant Solid Tumors","route":"/trials/nct06040541/"},{"id":"nct07805954","kind":"trial","name":"Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mut","route":"/trials/nct07805954/"},{"id":"nct07621718","kind":"trial","name":"Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-muta","route":"/trials/nct07621718/"},{"id":"nct06922591","kind":"trial","name":"Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients","route":"/trials/nct06922591/"}],"idea":[{"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/"}],"pairing":[{"id":"g12d-plus-pan-ras","kind":"pairing","name":"G12D-selective + pan-RAS(ON) inhibitor (zoldonrasib + daraxonrasib)","route":"/pairings/g12d-plus-pan-ras/"}],"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/"}]}}