{"entity":{"id":"avutometinib-defactinib","kind":"drug","name":"Avutometinib + defactinib","aka":["Avutometinib","Defactinib","Avutometinib and defactinib"],"tldr":"Avutometinib plus defactinib is the first treatment approved specifically for low-grade serous ovarian cancer, a slow-growing type driven by the RAS pathway.","summary":"Accelerated approval 8 May 2025 for adults with KRAS-mutated recurrent low-grade serous ovarian cancer after prior systemic therapy, based on RAMP 201 (ORR 44%, median DOR 31.1 months in KRAS-mutant disease). Avutometinib inhibits MEK and blocks RAF-driven MEK reactivation; defactinib blocks FAK, a resistance node. RAMP 301 (phase 3) is confirmatory; combinations in KRAS-mutant lung and pancreatic cancer are being explored.","status":"approved","asOf":"2026-09-07","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Avutometinib"}],"tags":[],"related":[],"cancers":["ovarian","low-grade-serous-ovarian-cancer"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["kras","fak"],"drugs":[],"companies":["verastem"],"institutions":[],"pathways":["ras-mapk"],"terms":["lgsoc"],"trials":["ramp-201"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Avmapki Fakzynja Co-Pack","code":"VS-6766 + VS-6063","modality":"Small-molecule RAF/MEK clamp + FAK inhibitor","mechanism":"Avutometinib is a dual RAF/MEK 'clamp' that prevents compensatory MEK phosphorylation; defactinib inhibits focal adhesion kinase, a feedback survival signal.","approvals":[{"region":"US","year":2025,"indication":"KRAS-mutated recurrent low-grade serous ovarian cancer after prior systemic therapy (accelerated)"}],"mechanismSteps":["Avutometinib binds MEK and locks RAF-MEK in an inactive complex","ERK signalling from mutant KRAS drops without feedback rebound","Defactinib blocks FAK, removing an adhesion-driven escape route","LGSOC cells arrest and regress over months"],"dosing":{"route":"Oral","schedule":"Avutometinib 3.2 mg twice weekly + defactinib 200 mg twice daily, 3 weeks on / 1 week off","monitoring":"Creatine kinase, liver enzymes, eye exams, skin","source":"https://www.onclive.com/view/accelerated-fda-approval-establishes-role-of-avutometinib-defactinib-in-kras-mutant-recurrent-low-grade-serous-ovarian-cancer"},"toxicity":[{"event":"Nausea","anyGradePct":67},{"event":"Diarrhoea","anyGradePct":58},{"event":"Rash / dermatitis acneiform","anyGradePct":50},{"event":"Creatine kinase increase","anyGradePct":61,"note":"RAMP 201 pooled, per FDA label summary"}],"access":[],"regulatoryEvents":[{"date":"2025-05-08","type":"accelerated-approval","region":"US","note":"Accelerated approval on RAMP 201; RAMP 301 confirmatory The confirmatory requirement was still open 1.4 years later, when the FDA's table was read.","source":"https://www.targetedonc.com/view/avutometinib-plus-defactinib-gains-fda-approval-in-kras-ovarian-cancer","indication":"Treatment of adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy"}]},"route":"/drugs/avutometinib-defactinib/","neighbours":{"cancer":[{"id":"low-grade-serous-ovarian-cancer","kind":"cancer","name":"Low-grade serous ovarian cancer","route":"/cancers/low-grade-serous-ovarian-cancer/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"fak","kind":"target","name":"FAK (PTK2)","route":"/targets/fak/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"}],"company":[{"id":"verastem","kind":"company","name":"Verastem Oncology","route":"/companies/verastem/"}],"pathway":[{"id":"caf-activation-desmoplasia","kind":"pathway","name":"Fibroblast activation, desmoplasia & matrix stiffness","route":"/pathways/caf-activation-desmoplasia/"},{"id":"invasion-ecm-degradation","kind":"pathway","name":"Invasion: proteases, adhesion & the invasive front","route":"/pathways/invasion-ecm-degradation/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"lgsoc","kind":"term","name":"Low-grade serous ovarian cancer (LGSOC)","route":"/terms/lgsoc/"}],"trial":[{"id":"nct07824960","kind":"trial","name":"Neoadjuvant Avutometinib/Defactinib and mFOLFIRINOX Combination Therapy in Pancreatic Adenocarcinoma","route":"/trials/nct07824960/"},{"id":"nct06369259","kind":"trial","name":"Open-label Phase 2 Study of Avutometinib (RAF/MEK Clamp) in Combination With Defactinib (FAK Inhibitor) and Cetuximab in Patients With Unresectable, Anti-EGFR-R","route":"/trials/nct06369259/"},{"id":"ramp-201","kind":"trial","name":"RAMP 201","route":"/trials/ramp-201/"},{"id":"nct07126158","kind":"trial","name":"Stereotactic Body Radiotherapy Plus FAK and RAF/MEK Inhibition in Advanced Pancreatic Adenocarcinoma","route":"/trials/nct07126158/"}]}}