mhn amivantamab coverage update: Prior Auth

Coverage Criteria

Initial Therapy — Covered when ALL of the following are met for NSCLC

Covered when ALL of the following are met for NSCLC:

Initial NSCLC criteria: 1. Diagnosis of recurrent, advanced, or metastatic non-small cell lung cancer (NSCLC); 2. Prescribed by or in consultation with an oncologist; 3. Patient is ≥ 18 years of age; 4. One of the following mutation and treatment scenarios is met (see nested logic); 5. Requested dose does not exceed the maximum indicated regimen in section V OR dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Mutation/treatment scenarios

a. EGFR exon 20 insertion: Disease is positive for EGFR exon 20 insertion mutation AND Rybrevant or Rybrevant Faspro is prescribed for one of the following: (i) first‑line in combination with carboplatin and pemetrexed; OR (ii) as a single agent for disease that has progressed on or after platinum‑based therapy.
b. Subsequent therapy after EGFR TKI: Rybrevant or Rybrevant Faspro is prescribed as subsequent therapy after progression on an EGFR tyrosine kinase inhibitor (e.g., erlotinib, afatinib (Gilotrif), lazertinib (Lazcluze), osimertinib (Tagrisso)) AND both: (i) disease is positive for EGFR exon 19 deletions OR exon 21 L858R substitution mutation; AND (ii) prescribed in combination with carboplatin and pemetrexed.
c. Combination with lazertinib (Lazcluze): Rybrevant or Rybrevant Faspro is prescribed in combination with lazertinib for disease positive for EGFR exon 19 deletion(s) or exon 21 L858R substitution mutation(s) AND one of: (i) prescribed as first‑line therapy; (ii) continuation of therapy following progression on the combination of Rybrevant/Rybrevant Faspro + lazertinib for asymptomatic disease, symptomatic brain lesions, or symptomatic limited systemic progression; OR (iii) prescribed as subsequent therapy following progression after prior therapies such as (1) Tagrisso for symptomatic systemic disease with multiple lesions OR (2) Tagrisso with (carboplatin or cisplatin) + pemetrexed.
d. Brain metastases: Member has brain metastases AND disease is positive for EGFR exon 19 deletion(s) or exon 21 L858R substitution mutation(s) AND Rybrevant/Rybrevant Faspro is prescribed in combination with either: (1) carboplatin and pemetrexed; OR (2) lazertinib.

Continuation Therapy — Covered for continuation when ALL of the following are met

Covered for continuation when ALL of the following are met:

Continued therapy criteria: 1. Member is currently receiving Rybrevant or Rybrevant Faspro via the Centene benefit, or submitted documentation supports current use and that the member has received therapy for at least 30 days; 2. Member is responding positively to therapy (clinical benefit); 3. If request is for a dose increase, the new dose does not exceed the maximum indicated regimen in section V OR the new dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval duration: Medicaid/HIM = 12 months; Commercial = 6 months or to member's renewal date, whichever is longer.

Covered indications and dosing notes — monotherapy and combination regimens per labeling and NCCN

Policy covers amivantamab for NSCLC when criteria per labeling and the NCCN Compendium are met; includes monotherapy and combination regimens.

Dosing regimen and indications: Weight‑based dosing for subcutaneous amivantamab/hyaluronidase (Rybrevant Faspro): Weeks 1–4, Day 1 weekly dosing then every 2 weeks thereafter. Body weight < 80 kg: 1,600 mg amivantamab + 20,000 units hyaluronidase (one vial). Body weight ≥ 80 kg: 2,240 mg amivantamab + 28,000 units hyaluronidase (one vial). IV amivantamab dosing follows the labeled IV regimen. Prescribed regimen must be FDA‑approved or recommended by NCCN; vial strengths must be selected to match required mg per dose.weight < 80 kg vs ≥ 80 kg

Refer to section V for maximum dose and full regimen details; initial weekly SC dosing given for 4 weeks then every 2 weeks thereafter.

Non-FDA approved indications for amivantamab products that are not specifically addressed in this policy are not authorized unless the provider submits sufficient documentation demonstrating efficacy and safety in accordance with the applicable off‑label use policies. For Commercial members, reference CP.CPA.09; for Health Insurance Marketplace, reference HIM.PA.154; and for Medicaid, reference CP.PMN.53. Documentation should follow the requirements cited in those policies to support any off‑label request.

Per the most recent compendium and guideline review, the policy has removed EGFR mutations G719X, S768I, and L861Q from the initial coverage criteria. This change reflects the NCCN compendium update that these specific mutation‑based indications are not supported and therefore are no longer included as approval pathways in initial therapy criteria.

Use of amivantamab (any formulation) for indications that are not FDA‑approved and not supported by the off‑label use policies is considered not authorized. Requests for off‑label coverage must comply with the referenced off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), and CP.PMN.53 (Medicaid).

Coding lists in this policy are provided for informational purposes only. Inclusion or exclusion of a code does not guarantee coverage, and claims may be denied if coding does not follow current professional coding guidance. Providers should verify and apply the most up‑to‑date coding guidance when submitting claims to reduce the risk of denial.

Coding and Billing

Referenced HCPCS / drug codesHCPCS

J9061	Injection, amivantamab-vmjw, 2 mg.
C9399	Unclassified drugs or biologicals.
J9999	Not otherwise classified, antineoplastic drugs

inv-09: Body weight cutoff for dosing

Weight-based cutoffMost dosing decisions for Rybrevant Faspro use a body weight cutoff of < 80 kg versus ≥ 80 kg

Dose for patients < 80 kg (SC)1,600 mg amivantamab + 20,000 units hyaluronidase per dose (1 vial)

Dose for patients ≥ 80 kg (SC)2,240 mg amivantamab + 28,000 units hyaluronidase per dose (1 vial)

Dosing schedule (SC)Weeks 1–4: Day 1 weekly; Week 5 and thereafter: every 2 weeks using the same weight-based dose

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for initial and continued therapy with Rybrevant (amivantamab) or Rybrevant Faspro (amivantamab/hyaluronidase). Requests must meet the policy clinical criteria for the requested indication (see Initial Approval Criteria and Continued Therapy sections).

Prior authorization required for both initial and continuation requests.
Approval durations: Medicaid/HIM — 12 months; Commercial — 6 months or to member renewal date, whichever is longer.

Documentation Required

Documentation Required to Support Request

Provider must submit supporting clinical documentation (e.g., office chart notes, diagnostic test results, pathology or molecular testing confirming EGFR exon 20 insertion or other specified mutation, imaging, and treatment history) demonstrating that the member meets all approval criteria. Failure to provide the requested documentation may result in denial of the request.

Initial Therapy Criteria

Initial Therapy — Initial approval criteria for NSCLC including diagnosis, prescriber specialty, age, mutation and prior therapy conditions

Initial approval criteria for NSCLC (detailed) — includes required diagnosis, prescriber specialty, age, mutation and prior therapy conditions.

Initial therapy nodes (detailed): 1. Diagnosis: recurrent, advanced, or metastatic NSCLC; 2. Prescriber: oncologist or in consultation with oncologist; 3. Age ≥ 18 years; 4. Must meet one of the mutation/treatment scenarios (a–d) specified in the policy: (a) EGFR exon 20 insertion with either first‑line combination with carboplatin + pemetrexed OR single‑agent after progression on platinum therapy; (b) subsequent therapy after progression on an EGFR TKI for EGFR exon 19 deletion or exon 21 L858R when prescribed with carboplatin + pemetrexed; (c) combination with lazertinib for EGFR exon 19 deletion or exon 21 L858R in specified settings (first‑line, continuation after progression for select situations, or subsequent therapy after prior specified regimens); (d) brain metastases with EGFR exon 19 deletion or exon 21 L858R when prescribed with carboplatin + pemetrexed or lazertinib; 5. Dose must not exceed maximum indicated regimen in section V or be supported by guidelines/literature (prescriber must submit evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Previously included mutations G719X, S768I, and L861Q have been removed per NCCN (see policy history).

Initial therapy dosing (SC) — initial dosing and indication details per PI and NCCN

Initial dosing for the subcutaneous formulation (Rybrevant Faspro) per prescribing information and NCCN:

Continuation / Maintenance Criteria

Continuation Therapy — requires current use and clinical benefit

Continuation approval requires current use and clinical benefit:

Continuation requirements: 1. Member is currently receiving Rybrevant or Rybrevant Faspro via the Centene benefit or documentation supports current use for ≥ 30 days; 2. Member demonstrates clinical benefit or positive response to therapy; 3. Dose increases must not exceed the maximum indicated regimen in section V OR must be supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or NCCN‑recommended.

Approval durations: Medicaid/HIM = 12 months; Commercial = 6 months or to member's renewal date.

Continuation therapy — continuation/maintenance options per NCCN compendium

Continuation and maintenance options per NCCN compendium and policy updates:

Continuation/maintenance options: Policy includes option for continuation of Rybrevant in combination with lazertinib (Lazcluze) per the NCCN Compendium and as subsequent therapy per labeling; continuation after progression on the combination may be allowed for asymptomatic disease, symptomatic brain lesions, or limited symptomatic systemic progression as specified in the policy.

Step Therapy / Therapeutic Alternatives

Therapeutic alternative	Example agents / notes
Platinum-based chemotherapy
Examples: cisplatin, carboplatin; dosing regimens vary and may require prior authorization per formulary
EGFR tyrosine kinase inhibitors (class)
Examples: erlotinib (Tarceva), gefitinib (Iressa), afatinib (Gilotrif), osimertinib (Tagrisso), dacomitinib (Vizimpro); dosing varies
Prescriber documentation
Provider may need to document clinical rationale if selecting amivantamab instead of listed alternatives; alternatives may be required per formulary

Step	Requirement / sequencing	Notes
1
Prior progression on an EGFR tyrosine kinase inhibitor is required for certain subsequent-therapy indications
Sequencing language updated from a specific agent requirement ('Tagrisso') to the EGFR TKI class; aligns with new labeled indication for combination regimens
1
Initial therapy options may include combination with carboplatin + pemetrexed or with lazertinib depending on mutation status and line of therapy
Refer to mutation-specific criteria in policy; continuation options added for combination with lazertinib per NCCN

Quantity Limits & Product Availability

inv-27: amivantamab/hyaluronidase (Rybrevant Faspro) — multiple vial strengths; vial strengths must be selected to match required mg per dose

Vial selection requirementVial strengths must be selected to match the required mg of amivantamab and hyaluronidase units per dose

Available Rybrevant Faspro vial strengths1,600 mg / 20,000 units; 2,240 mg / 28,000 units; 2,400 mg / 30,000 units; 3,520 mg / 44,000 units

Concentration consistencyEach Faspro vial contains amivantamab at 160 mg/mL and hyaluronidase at 2,000 units/mL

Matching to dose examplesFor weight-based SC dosing, use one vial corresponding to the prescribed mg/units (e.g., <80 kg -> 1,600 mg vial; ≥80 kg -> 2,240 mg vial)

Site of Care Considerations

Note

Administration settings — IV and SC formulations

Both IV (Rybrevant) and SC (Rybrevant Faspro) formulations are covered with weight‑based dosing regimens; administration may occur in infusion center, office, or hospital outpatient settings as appropriate for the formulation.

IV formulation: weight‑based IV dosing per labeled regimens (split infusion in Week 1 for some regimens)
SC formulation: weight‑based subcutaneous dosing with hyaluronidase (Rybrevant Faspro) per labeled regimens

Note

Site of care — SC (Faspro) suitable for office/infusion

The subcutaneous Rybrevant Faspro formulation allows SC administration in office or infusion center settings; the IV formulation (Rybrevant) is supplied as a solution for injection in single‑dose vials.

Rybrevant Faspro: SC administration, multiple single‑dose vial strengths available
Rybrevant (IV): solution for injection in single‑dose vial (350 mg/7 mL)

Background

Amivantamab is a bispecific monoclonal antibody that targets both EGFR and MET receptors. A new subcutaneous formulation, amivantamab/hyaluronidase (Rybrevant Faspro), combines amivantamab with hyaluronidase to enable subcutaneous administration. The policy update adds Faspro vial strengths and reflects that the Faspro formulation is intended to permit SC delivery while the original Rybrevant product remains an intravenous formulation.

Definitions

inv-19: EGFR exon 20 insertion — definition and relevance to approvals

DefinitionEGFR exon 20 insertion is a specific mutation type in the EGFR gene associated with certain NSCLC cases and is a labeled indication context in this policy

Relevance to therapyPresence of EGFR exon 20 insertion mutations informs eligibility for amivantamab regimens, including first‑line combination with carboplatin + pemetrexed or single‑agent use after platinum progression

Testing requirementMutation detection must be by an FDA‑approved test per policy expectations (refer to labeling and NCCN guidance)

inv-20: Rybrevant Faspro — key definition and available vial strengths

Agent definitionRybrevant Faspro is the subcutaneous formulation combining amivantamab with hyaluronidase to enable SC administration

Commercial vial strengths

OpenPayer

Amivantamab (Rybrevant) and Amivantamab/Hyaluronidase (Rybrevant Faspro) coverage