CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Avmapki Fakzynja Co-pack (avutometinib and defactinib) — Coverage Criteria

Defines coverage and prior authorization criteria for Avmapki Fakzynja Co-pack in adult members with KRAS‑mutated recurrent low‑grade serous ovarian cancer; includes prior authorization, continuation rules, required supporting documentation, dosing limits, and exclusions.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyAvmapki Fakzynja Co-pack (avutometinib and defactinib) — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateJune 2025

Next Review DateN/A

Key ActionSubmit prior authorization and supporting documentation per FDA labeling, CMS‑recognized compendia, NCCN/ASCO guidelines, or acceptable peer‑reviewed literature.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

KRAS‑mutated LGSOCIndication

J8999Billing code

24 caps / 42 tabsMonthly dosing limit

June 2025Policy date

Coverage and Medical Necessity Criteria

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inv-01: Initial therapy — covered indication

Covered when ALL of the following are met

Covered Indication: Adult member with KRAS‑mutated recurrent low‑grade serous ovarian cancer (LGSOC)

must have received prior systemic therapy

inv-02: Continuation therapy

Continuation requests may be approved when ALL of the following are met

Continuation criteria: Member has not experienced disease progression on the requested medication; the requested medication was used within the last year without a lapse of more than 30 days of having an active authorization; no additional medications are being added to the continuation request.

Continuation exemption from full policy review

Requests will be excluded when any of the following apply: the member has KRAS wild‑type low‑grade serous ovarian cancer; the member experienced disease progression while taking the Avmapki Fakzynja Co‑pack (avutometinib and defactinib); the co‑pack is being used concurrently with other anticancer therapies; or dosing exceeds established single‑dose limits of Avmapki (avutometinib) 3.2 mg and Fakzynja (defactinib) 200 mg.

Coverage will also be denied if the requested treatment exceeds the monthly maximums of 24 Avmapki (0.8 mg) capsules/month and 42 Fakzynja (200 mg) tablets/month. These dosing limits must be respected on all authorization requests.

Off‑label uses for indications that lack sufficient evidence or are not generally accepted by the medical community are considered investigational and not covered. Evidence insufficiency is assessed using the policy’s criteria, including representativeness of the patient population, whether the exact regimen is represented in published evidence, whether outcomes are clinically meaningful (for example ASCO‑recommended thresholds such as hazard ratio < 0.80 or survival benefit of ≥ 3 months for OS/PFS), study design appropriateness, and the strength of evidence (with case reports and meeting abstracts generally considered inadequate).

Uses of the Avmapki Fakzynja Co‑pack that are outside the labeled or recognized indications and that do not have adequate supporting evidence are considered investigational and will be denied. The policy defines insufficient evidence by specific considerations: whether the published literature adequately represents the clinical characteristics of the patient and cancer, whether the exact regimen is represented, whether reported outcomes are clinically meaningful (per ASCO guidance), whether the experimental design is appropriate, and the overall level of evidence (noting that case reports and unpublished abstracts lack sufficient support).

Providers requesting off‑label use should supply high‑quality, peer‑reviewed evidence or CMS‑recognized compendia support that directly addresses the patient characteristics and regimen; otherwise the request is subject to denial as investigational.

Regimen	Indication	Billing code	Coverage status
Avmapki Fakzynja Co-pack (avutometinib and defactinib)	KRAS‑mutated recurrent low‑grade serous ovarian cancer (LGSOC) in adult members after prior systemic therapy	J8999	Covered with criteria

Prior Authorization, Documentation, and Denial Conditions

Prior Authorization

Prior Authorization Required

Prior authorization required for Avmapki Fakzynja Co-pack (avutometinib and defactinib). Continuation requests are eligible if the member has not experienced disease progression on the requested medication, the medication was used within the last year without a lapse of more than 30 days of an active authorization, and no additional medications are being added to the continuation request.

Prior authorization required
Continuation requests allowed when no progression, <30-day lapse, and no new drugs added

Documentation Required

Supporting Documentation Required

Provider must submit documentation supporting the requested use drawn from FDA labeling, CMS‑recognized compendia, NCCN or ASCO guidelines, or peer‑reviewed literature that meets CMS standards per the Medicare Benefit Policy Manual Chapter 15.

Acceptable sources: FDA approved product labeling; CMS‑recognized compendia; NCCN; ASCO clinical guidelines; peer‑reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15 requirements

Denial Risk

Denial Triggers / Exclusion Conditions

Requests should be denied or are excluded for members with KRAS wild‑type LGSOC, documented disease progression while taking the co‑pack, concurrent use with other anticancer therapies, dosing above single‑dose limits (Avmapki 3.2 mg; Fakzynja 200 mg), or monthly quantity limits (Avmapki >24 capsules (0.8 mg) per month; Fakzynja >42 tablets (200 mg) per month). Investigational or off‑label uses lacking sufficient evidence or not supported by CMS compendia/acceptable peer‑reviewed literature are also excluded.

Exclusions: KRAS wild‑type LGSOC
Disease progression on requested medication
Concurrent anticancer therapies
Single dose limits: Avmapki 3.2 mg; Fakzynja 200 mg
Monthly limits: Avmapki 24 (0.8 mg) capsules; Fakzynja 42 (200 mg) tablets
Investigational/off‑label indications without sufficient CMS‑recognized or acceptable peer‑reviewed evidence

Key Terms and Definitions

inv-13: Low-grade serous ovarian cancer (LGSOC)

Histologic subtypeLow-grade serous ovarian cancer (LGSOC)

Clinical contextCovered indication: adult members with KRAS-mutated recurrent LGSOC who have received prior systemic therapy

Line of therapyRecurrent disease after prior systemic therapy

inv-14: Insufficient/Investigational use

DefinitionInsufficient/Investigational use: off-label indications not supported by CMS-recognized compendia or acceptable peer-reviewed literature

Evidence considerationsIncludes assessment of representativeness of patient/cancer characteristics, regimen matching, and clinically meaningful outcomes

Study design weightNon-randomized trials may support evidence; case reports and abstracts without full articles generally lack adequate support

Background and Drug Description

Avmapki Fakzynja Co‑pack combines avutometinib and defactinib and, under this policy, is indicated for adult patients with KRAS‑mutated recurrent low‑grade serous ovarian cancer (LGSOC) who have received prior systemic therapy. Clinical use should align with FDA labeling, CMS‑recognized compendia, NCCN/ASCO guidance, or acceptable peer‑reviewed literature.

This policy also establishes key dosing and use safeguards: single‑dose limits of Avmapki 3.2 mg and Fakzynja 200 mg, and monthly maximums of 24 Avmapki (0.8 mg) capsules and 42 Fakzynja (200 mg) tablets. Use is not permitted concurrently with other anticancer therapies and will be excluded if disease progression occurred while on the co‑pack or if the tumor is KRAS wild‑type.

OpenPayer

Avmapki Fakzynja Co-pack (avutometinib and defactinib) — Coverage Criteria

Coverage and Medical Necessity Criteria

Billing and Quantity Limits

Prior Authorization, Documentation, and Denial Conditions

Therapy Line Requirements

Required Biomarker Testing

Key Terms and Definitions

Background and Drug Description