CurrentmhnPolicy CP.PHAR.731

Clinical Policy: Avutometinib; Defactinib (Avmapki Fakzynja Co-Pack)

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 Summary

Payermhn

PolicyClinical Policy: Avutometinib; Defactinib (Avmapki Fakzynja Co-Pack)

Policy CodePolicy CP.PHAR.731

Change TypeInitial policy creation

Effective DateSep 1, 2025

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results or other clinical information) supporting that member meets all approval criteria.

SourceLink

POLICY UPDATE CHANGES

Policy created May 15, 2025 with P&T approval date 08.25.25.

1Covered Indication (FDA-approved)

6/12Approval durations (initial/continued months)

3Required prior systemic therapy

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

Diagnoses / Indications Not Authorized

III. Diagnoses/Indications Not Authorized

Not covered unless exception applies:

Non-FDA approved indications that are not addressed in this policy are not authorized unless there is sufficient documentation of efficacy and safety per off-label use policies
References: CP.CPA.09, HIM.PA.154, CP.PMN.53

Provider Actions & Prior Authorization Requirements

Documentation Required

Submission of supporting documentation

Provider must submit office chart notes, laboratory results, or other clinical information supporting that the member meets all approval criteria.

Prior Authorization

Prescriber specialty requirement

The prescription must be by an oncologist or written in consultation with an oncologist.

Prior Authorization

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.

Billing Rule

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.

Definitions and Policy Metadata

LGSOC (term)low-grade serous ovarian cancer

FDA (term)Food and Drug Administration

Policy numberCP.PHAR.731

Effective date09.01.25

Last review date08.25

Payer metadata (line of business)Commercial, HIM, Medicaid