Clinical Policy: Avutometinib; Defactinib (Avmapki Fakzynja Co-Pack)
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Defines medical necessity criteria, initial and continued authorization requirements, dosing limits, contraindications, therapeutic alternatives, and prior authorization expectations for Avmapki Fakzynja Co-Pack across Commercial, HIM, and Medicaid lines of business.
Policy created May 15, 2025 with P&T approval date 08.25.25.
Coverage Summary & Indications
Avmapki Fakzynja Co-Pack received accelerated approval for the treatment of adults with KRAS‑mutated recurrent low‑grade serous ovarian cancer (LGSOC) who have received prior systemic therapy. Coverage stance: covered_with_criteria. Scope: applies to Commercial, HIM, and Medicaid lines of business.
Initial Therapy Criteria
I. Initial Approval Criteria - Ovarian Cancer
Covered when ALL of the following are met:
- Diagnosis of LGSOC
- Prescribed by or in consultation with an oncologist
- Age ≥ 18 years≥ 18 years
- Disease is recurrent
- Disease is positive for KRAS mutation
- Avmapki Fakzynja Co-Pack is not prescribed concurrently with any other agents for LGSOC
- Member has received prior systemic therapy (see Appendix B)
- Member must use avutometinib and defactinib, if available, unless contraindicated or clinically significant adverse effects are experienced
Dose requirement (a or b)
a. Dose does not exceed for the first 3 weeks of every 4-week cycle
- i: Avmapki: 6.4 mg (8 capsules) per week≤ 6.4 mg per week
- ii: Fakzynja: 400 mg (2 tablets) per day≤ 400 mg per day
- b: Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)
- Prescribed regimen must be FDA-approved or recommended by NCCN
I. Initial Approval Criteria - Other diagnoses/indications
If not listed above, meet ONE of the following:
- 1: If drug label recently changed within last 6 months and change not reflected in policy, follow applicable formulary/no-coverage or non-formulary policy
References: CP.CPA.190, HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16
- 2: If requested use is not listed under coverage-not-authorized section and above does not apply, refer to off-label use policy for relevant line of business
References: CP.CPA.09, HIM.PA.154, CP.PMN.53
Continuation Therapy Criteria
II. Continued Therapy - Ovarian Cancer
Continued coverage when ALL of the following are met:
- Currently receiving medication via Centene benefit, or documentation supports current receipt for a covered indication and ≥ 30 days of therapy≥ 30 days
- Member is responding positively to therapy
- Avmapki Fakzynja Co-Pack is not prescribed concurrently with any other agents for LGSOC
- Member must use avutometinib and defactinib, if available, unless contraindicated or clinically significant adverse effects are experienced
Dose increase requirement (a or b)
a. New dose does not exceed for the first 3 weeks of every 4-week cycle
- i: Avmapki: 6.4 mg (8 capsules) per week≤ 6.4 mg per week
- ii: Fakzynja: 400 mg (2 tablets) per day≤ 400 mg per day
- b: New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)
- Prescribed regimen must be FDA-approved or recommended by NCCN
II. Continued Therapy - Other diagnoses/indications
If not listed above, meet ONE of the following:
- 1: If drug label recently changed within last 6 months and change not reflected in policy, follow applicable formulary/no-coverage or non-formulary policy
References: CP.CPA.190, HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16
- 2: If requested use is not listed under coverage-not-authorized section and above does not apply, refer to off-label use policy for relevant line of business
References: CP.CPA.09, HIM.PA.154, CP.PMN.53
Applicable Codes
| avumetinib 0.8 mg capsule | co-packaged capsule |
| defactinib 200 mg tablet | co-packaged tablet |
Provider Actions & Prior Authorization Requirements
Submission of supporting documentation
Provider must submit office chart notes, laboratory results, or other clinical information supporting that the member meets all approval criteria.
Prescriber specialty requirement
The prescription must be by an oncologist or written in consultation with an oncologist.
Dose justification for off-guideline dosing
If the requested dose exceeds the specified limits, the prescriber must submit supporting evidence from practice guidelines or peer‑reviewed literature to justify the off‑guideline dosing.
Use of both agents when available
Requests must use both avutometinib and defactinib if both agents are available, unless there is a contraindication or the member experiences clinically significant adverse effects.
Clinical Evidence & Approval Basis
Approval basis: Accelerated approval based on tumor response rate and duration of response; continued approval may require verification of clinical benefit in a confirmatory trial. Primary references: Avmapki Fakzynja Co-Pack Prescribing Information (Verastem, May 2025) and the NCCN Drugs and Biologics Compendium and ovarian cancer guideline.
Background
Avmapki Fakzynja Co-Pack is a co‑packaged product containing avutometinib and defactinib; both agents are kinase inhibitors. The product is supplied as avumetinib 0.8 mg capsules and defactinib 200 mg tablets in a co‑packaged presentation.
The co‑pack is approved under an accelerated approval pathway for the indication: treatment of adult patients with KRAS‑mutated recurrent low‑grade serous ovarian cancer (LGSOC) who have received prior systemic therapy. Dosing recommended for LGSOC during the first 3 weeks of each 4‑week cycle is Avmapki 3.2 mg PO twice weekly (Day 1 and Day 4) and Fakzynja 200 mg PO BID, until disease progression or unacceptable toxicity.
Revision History
Policy created May 15, 2025 with P&T approval date 08.25.25. Initial policy creation and approval; no prior version indicated.
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