OnCo
drugsProductApproved2025

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.

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Avutometinib
PubChem
Mechanism, step by step
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1.Avutometinib binds MEK and locks RAF-MEK in an inactive complex

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.
Brand / code
Avmapki Fakzynja Co-Pack · VS-6766 + VS-6063
Dosing & schedule
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.

Not appraisedSearch NICE
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.

Regulatory

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  1. 8 May 2025ApprovalUS

    Accelerated approval on RAMP 201; RAMP 301 confirmatory source

Approvals

RegionYearIndication
US2025KRAS-mutated recurrent low-grade serous ovarian cancer after prior systemic therapy (accelerated)

Safety

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Toxicity profile
Adverse eventAny gradeGrade 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

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ClinicalTrials.gov · phase 2/3
refreshed 2026-09-09
22 studies12 recruiting21 Phase 21 Phase 3
Search “Avutometinib” on ClinicalTrials.gov →
Counts are from a name search and may include unrelated studies; up to 100 studies are summarised.

Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Avutometinib + defactinib
intervention: Avutometinib
Open on ClinicalTrials.gov →

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Latest papers

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Literature trend6 papers in the last 12 monthsHow this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

Query 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.

Connected

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