# Avutometinib + defactinib

Source: https://onco.cc/drugs/avutometinib-defactinib/  
OnCo record `avutometinib-defactinib` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-07
- Also known as: Avutometinib; Defactinib; Avutometinib and defactinib
- 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: US 2025: KRAS-mutated recurrent low-grade serous ovarian cancer after prior systemic therapy (accelerated)
- Dosing: Oral; Avutometinib 3.2 mg twice weekly + defactinib 200 mg twice daily, 3 weeks on / 1 week off

## Sources

- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Avutometinib

## Connected records

- cancers: [Low-grade serous ovarian cancer](https://onco.cc/cancers/low-grade-serous-ovarian-cancer/), [Ovarian cancer](https://onco.cc/cancers/ovarian/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [FAK (PTK2)](https://onco.cc/targets/fak/), [KRAS](https://onco.cc/targets/kras/)
- companies: [Verastem Oncology](https://onco.cc/companies/verastem/)
- pathways: [Fibroblast activation, desmoplasia & matrix stiffness](https://onco.cc/pathways/caf-activation-desmoplasia/), [Invasion: proteases, adhesion & the invasive front](https://onco.cc/pathways/invasion-ecm-degradation/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- terms: [Low-grade serous ovarian cancer (LGSOC)](https://onco.cc/terms/lgsoc/)
- trials: [Neoadjuvant Avutometinib/Defactinib and mFOLFIRINOX Combination Therapy in Pancreatic Adenocarcinoma](https://onco.cc/trials/nct07824960/), [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](https://onco.cc/trials/nct06369259/), [RAMP 201](https://onco.cc/trials/ramp-201/), [Stereotactic Body Radiotherapy Plus FAK and RAF/MEK Inhibition in Advanced Pancreatic Adenocarcinoma](https://onco.cc/trials/nct07126158/)

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