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.
Avutometinib is a dual RAF/MEK 'clamp' that prevents compensatory MEK phosphorylation; defactinib inhibits focal adhesion kinase, a feedback survival signal. Connects to KRAS and FAK (PTK2).
1.Avutometinib binds MEK and locks RAF-MEK in an inactive complex
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance: how tumours escape each drug class · Lines of therapy.
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.
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.
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.
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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Treatment of adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy
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
| 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.
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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" OR TITLE:"Avutometinib" OR ABSTRACT:"Avutometinib" OR TITLE:"Defactinib" OR ABSTRACT:"Defactinib" OR TITLE:"Avutometinib and defactinib" OR ABSTRACT:"Avutometinib and defactinib") 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.
Shares Verastem Oncology, Low-grade serous ovarian cancer, Ovarian cancer.
Shares Verastem Oncology, Low-grade serous ovarian cancer, Ovarian cancer.
Shares RAMP 201, Low-grade serous ovarian cancer.
Shares Invasion: proteases, adhesion & the invasive front, Fibroblast activation, desmoplasia & matrix stiffness, RAS / RAF / MEK / ERK (MAPK), KRAS.
Shares Invasion: proteases, adhesion & the invasive front, Fibroblast activation, desmoplasia & matrix stiffness.