Avutometinib + defactinib
Avutometinib plus defactinib is the first treatment approved specifically for low-grade serous ovarian cancer, a slow-growing type driven by the RAS pathway.
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.
1.Avutometinib binds MEK and locks RAF-MEK in an inactive complex
- 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: www.onclive.com/view/accelerated-fda-approval-establishes-role-of-avutometinib-defactinib-in-kras-mutant-recurrent-low-grade-serous-ovarian-cancer. Doses are for orientation; the current label governs.
- Medicare
- Part D (self-administered)
Oral, self-administered, so it is a Part D drug: covered through a stand-alone Part D plan or Medicare Advantage drug benefit, usually on the specialty tier with 25 to 33% coinsurance until the annual cap ($2,000 in 2025, $2,100 in 2026). FDA accelerated approval May 2025 for KRAS-mutant low-grade serous ovarian cancer.
- Commercial insurance
- covered with prior authorisation
Covered for FDA-labelled and NCCN-listed uses, but almost always behind prior authorisation confirming diagnosis, biomarker and line of therapy; dispensed through a specialty pharmacy. KRAS mutation documented; a rare indication most plans review individually.
Part D out-of-pocket capped at $2,000 (2025) / $2,100 (2026). Medicare patients cannot use manufacturer co-pay cards; charity funds (PAN, HealthWell, CancerCare) and the Extra Help subsidy are the routes.
Sources: Medicare.gov: Drug coverage (Part D) · Medicare.gov: Costs for Medicare drug coverage (annual out-of-pocket cap). Not medical or financial advice; verify with your plan.
- Notes
- No UK marketing authorisation as of September 2026, so no NICE appraisal. Access only through a clinical trial or a company early access scheme.
- NHS England
- Not routinely funded
Sources: NICE search: avutometinib with defactinib. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
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- 8 May 2025ApprovalUS
Accelerated approval on RAMP 201; RAMP 301 confirmatory source
Approvals
| Region | Year | Indication |
|---|---|---|
| US | 2025 | KRAS-mutated recurrent low-grade serous ovarian cancer after prior systemic therapy (accelerated) |
| Adverse event | Any grade | Grade 3+ |
|---|---|---|
| Nausea | 67% | — |
| Diarrhoea | 58% | — |
| Rash / dermatitis acneiform | 50% | — |
| Creatine kinase increase | 61% | — |
RAMP 201 pooled, per FDA label summary. Events listed without rates were not read from a primary source; see the label. Blank cells mean the figure was not sourced, not that it is zero.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Landmark trials in OnCo
Latest papers
topQuery for this drug: (TITLE:"Avutometinib + defactinib" OR ABSTRACT:"Avutometinib + defactinib" OR TITLE:"Avmapki Fakzynja Co-Pack" OR ABSTRACT:"Avmapki Fakzynja Co-Pack" OR TITLE:"VS-6766 + VS-6063" OR ABSTRACT:"VS-6766 + VS-6063") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Avutometinib + defactinib, not a curated reading list.