Avutometinib/Defactinib — Drug Monograph

Brand names: Avmapki Fakzynja Co-Pack, Avmapki, Fakzynja

Drug class: Other

Mechanism of Action

Avmapki Fakzynja Co-Pack is an FDA-approved dual-pathway co-pack pairing avutometinib, a RAF/MEK clamp that inhibits MEK kinase activity and prevents its reactivating phosphorylation by RAF, with defactinib, a focal adhesion kinase (FAK) inhibitor. In KRAS-mutated low-grade serous ovarian cancer, MEK inhibition alone triggers adaptive FAK-mediated resistance; co-inhibiting FAK blunts that escape, producing deeper and more durable MAPK-pathway suppression than either agent alone.

FDA Indications

• KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) in adults who have received prior systemic therapy (accelerated approval)

Common Side Effects

• Increased creatine phosphokinase (CPK)
• Nausea
• Fatigue
• Increased AST
• Rash
• Diarrhea
• Musculoskeletal pain
• Edema
• Decreased hemoglobin (anemia)
• Increased ALT
• Vomiting
• Increased blood bilirubin
• Increased triglycerides
• Dermatitis acneiform
• Vitreoretinal disorders
• Stomatitis
• Pruritus
• Visual impairment

Clinical Pearl

The Avmapki Fakzynja Co-Pack is a rare regulatory entity — the FDA approved avutometinib (RAF/MEK clamp) and defactinib (FAK inhibitor) together as a single co-packaged targeted regimen for KRAS-mutated recurrent low-grade serous ovarian cancer. Each component has a different cadence on a shared 4-week cycle (avutometinib twice weekly on Days 1 and 4; defactinib twice daily), both dosed 3 weeks on / 1 week off. Its overlapping-toxicity profile breaks single-agent paradigms and demands three…

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