ModifiedHealth NetPolicy CP PHAR.544

Amivantamab-vmjw (Rybrevant) for NSCLC

Medical necessity and coverage criteria for amivantamab-vmjw (Rybrevant) for treatment of non-small cell lung cancer (NSCLC) across Commercial, HIM, and Medicaid lines of business for Health Net/Centene-affiliated plans.

Policy Summary

PayerHealth Net

PolicyAmivantamab-vmjw (Rybrevant) for NSCLC

Policy CodePolicy CP PHAR.544

Change TypeAdded new combination indicationsdosing and criteria revisions

Effective Date09.01.21

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, oncologist involvement, mutation test results, and evidence of prior progression when required.

SourceLink

POLICY UPDATE CHANGES

Added criteria for new indication of first-line treatment of adults with NSCLC in combination with lazertinib and for combination with carboplatin and pemetrexed in certain EGFR mutation contexts.

Corrected initial dosing schedule for monotherapy to weekly for 5 weeks (with split initial infusion) then every 2 weeks thereafter.

Added criteria for new indication in combination with carboplatin and pemetrexed for NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations after progression on EGFR tyrosine kinase inhibitor.

Removed requirement for presence of symptomatic systemic disease with multiple lesions for tumors positive for EGFR exon 18 (G719X), exon 20 (S768I), or exon 21 (L861Q) based on NCCN compendium update.

Revised approval duration for Commercial line of business to 6 months or to the member's renewal date, whichever is longer.

Per NCCN Compendium, added combination Rybrevant + Lazcluze as continuation option therapy.

6 monthsInitial approval duration commercial

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Coverage Criteria

inv-01: Initial Therapy Criteria

Covered when ALL of the following are met

Initial Approval Criteria

Mutation/Indication options: a) Disease positive for EGFR exon 20 insertion mutations, and Rybrevant is prescribed for either (i) as a single agent for disease that has progressed on or after platinum-based therapy OR (ii) first-line therapy in combination with carboplatin and pemetrexed; b) Rybrevant is prescribed as subsequent therapy after progression on an EGFR tyrosine kinase inhibitor AND disease is positive for a sensitizing EGFR mutation (e.g., exon 18 G719X) AND prescribed in combination with carboplatin and pemetrexed; c) Rybrevant is prescribed in combination with lazertinib for disease positive for EGFR exon 19 deletions or exon 21 L858R substitution mutations (first-line) with continuation options as specified in policy;
Dosing limits and regimen must follow Section V dosing and FDA/NCCN recommendations.
Dose and weight-based vial limits: For single-agent or combination with lazertinib: weekly dosing for 5 weeks (split initial infusion) then every 2 weeks; weight-based vial counts and mg limits apply (see dosing table). For combination with carboplatin and pemetrexed: weekly dosing x4 (split initial infusion) then every 3 weeks; weight-based vial counts and mg limits apply.80 kg
Specific mg and vial counts by weight are in dosing section.

inv-02: Continuation Therapy

Covered when ALL of the following are met for continuation

Continued Therapy: 1) Member currently receiving medication via Centene benefit or documentation supports member has received Rybrevant for at least 30 days; 2) Diagnosis of non-small cell lung cancer (must meet all); 3) Member is responding positively to therapy; 4) New dose does not exceed the appropriate weight-based dose per the dosing regimen for the prescribed regimen (every 2 weeks for single agent or with lazertinib; every 3 weeks for combination with carboplatin and pemetrexed); 5) If request is for a dose increase, the increase is supported by practice guidelines or peer-reviewed literature and appropriate documentation is provided.

Prescribed regimen must be FDA-approved or recommended by NCCN.

inv-03: Coverage criteria for amivantamab-vmjw

Covered when ALL of the following are met for the new combination indication

Labeled combination indication for NSCLC: NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test, AND disease progression on an EGFR tyrosine kinase inhibitor; Rybrevant prescribed in combination with carboplatin and pemetrexed for this indication.

Added to align with labeled indication and requires documentation of mutation and prior progression on an EGFR TKI.

Off-label EGFR mutations (historical): For disease positive for EGFR exon 18 (G719X), exon 20 (S768I), or exon 21 (L861Q): the prior requirement for presence of symptomatic systemic disease with multiple lesions has been removed per NCCN Compendium updates.

Change implemented in 3Q 2025 annual review.

Requests for uses that are not FDA‑approved and not specifically addressed in this policy are not authorized unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), or CP PMN.53 (Medicaid).

This document segment does not list any explicit absolute exclusions. Updates recorded during the RT4 and 3Q 2025 reviews revised and clarified indication-specific requirements (for example, additions for combination regimens and removal of certain symptomatic‑disease requirements per NCCN) but did not add standalone absolute exclusions.

Uses that are non‑FDA approved and lack adequate supporting evidence per the referenced off‑label use policies may be determined to be not medically necessary and therefore not covered.

Per the policy updates reflected in RT4 and the 3Q 2025 annual review, prior conditional requirements were modified: the policy added labeled combination indications (for example, with carboplatin/pemetrexed for NSCLC with EGFR exon 19 deletions or exon 21 L858R after progression on an EGFR TKI) and removed the previous requirement that tumors positive for certain off‑label EGFR mutations (exon 18 G719X, exon 20 S768I, exon 21 L861Q) have symptomatic systemic disease with multiple lesions, consistent with NCCN compendium changes.

Coding and Billing

HCPCS CodesHCPCS

J9061

Injection, amivantamab-vmjw, 2 mg

No explicit codes listed in this document segmentmixed

No codes listed

Body weight dosing threshold

Body weight dosing threshold80 kg

Vial count determinationWeight-based vial counts and mg dosing reference dosing table (see Section V)

Dosing regimens affectedApplies to both monotherapy and combination regimens for Rybrevant

(no entry)

NotesNo data provided for this placeholder item in the brief or source document.

ActionRemove or populate with specific threshold/code if available in source materials.

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation (e.g., office chart notes, pathology or molecular testing reports, radiology reports, and lab results) showing the member meets all approval criteria, including diagnosis, oncologist prescribing or consultation, and any prior therapies attempted.

Prescriber: oncologist or in consultation with an oncologist
Required documentation: office chart notes, lab results, pathology/molecular testing, radiology reports

Documentation Required

Progression Documentation Required

Requests must include clear documentation that the patient has progressed on prior therapy when progression is required by the criteria. Progression documentation should include dates, imaging or clinical notes demonstrating disease progression, and details of the prior EGFR tyrosine kinase inhibitor used.

Document prior progression on an EGFR TKI when criteria specify prior progression

Background

Amivantamab‑vmjw (Rybrevant) is a bispecific antibody directed against EGFR and MET. It is indicated for treatment of adults with certain EGFR‑mutated non‑small cell lung cancer (NSCLC), including monotherapy use for tumors with EGFR exon 20 insertion mutations and combination regimens (for example with lazertinib or with carboplatin plus pemetrexed) for specified EGFR mutation contexts per the product labeling and NCCN recommendations.

Definitions and Abbreviations

EGFR exon 20 insertion mutations — definition

TermEGFR exon 20 insertion mutations

Definition (brief)Insertions in exon 20 of the epidermal growth factor receptor (EGFR) gene associated with NSCLC

RelevanceIndication for single-agent Rybrevant when disease has progressed on or after platinum-based chemotherapy

NCCN — National Comprehensive Cancer Network

AcronymNCCN = National Comprehensive Cancer Network

RoleUsed as compendium/guideline source to revise mutation-related criteria and continuation options

Policy impact

Line of Therapy

inv-24: first-line | second-line

Line options: First-line: Rybrevant in combination with lazertinib for EGFR exon 19 or exon 21 L858R mutations, or Rybrevant in combination with carboplatin and pemetrexed for EGFR exon 20 insertion mutations; Subsequent therapy (second-line): monotherapy for EGFR exon 20 insertions after progression on platinum-based chemotherapy or combination with carboplatin and pemetrexed after progression on an EGFR tyrosine kinase inhibitor for sensitizing EGFR mutations.

See specific criteria sets for mutation and regimen details.

inv-25: second-line

Post-EGFR TKI progression: Use of Rybrevant in combination with carboplatin and pemetrexed for NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations following progression on an EGFR tyrosine kinase inhibitor.

This represents the labeled second-line combination indication and requires documentation of prior progression on an EGFR TKI.

Biomarker Requirements

EGFR exon 20 insertion — as detected by an FDA-approved test

Detection standardEGFR exon 20 insertion as detected by an FDA-approved test

Indication linkRequired for single-agent Rybrevant indication after progression on platinum-based chemotherapy

Label referenceFDA-approved test requirement referenced in FDA Approved Indication(s)

EGFR exon 19 deletion or exon 21 L858R — as detected by an FDA-approved test

Detection standardEGFR exon 19 deletion or exon 21 L858R as detected by an FDA-approved test

Indication linkRequired for first-line combination with lazertinib per FDA labeling

Covered Regimens and Dosing

Regimen	Body weight < 80 kg — Week 1 split infusion (Day 1 / Day 2)	Body weight ≥ 80 kg — Week 1 split infusion (Day 1 / Day 2)	Week 2–4 (weekly) or Week 2 and thereafter (monotherapy) — dose (vials)	Maintenance (q2w monotherapy or q3w combination) — dose (vials)
Monotherapy (single agent)
Day 1: 350 mg (1 vial); Day 2: 700 mg (2 vials)
Day 1: 350 mg (1 vial); Day 2: 1,050 mg (3 vials)
Week 2 and thereafter (weekly during initial 5-week induction then q2w maintenance): 1,050 mg (3 vials)
q2 weeks maintenance: 1,050 mg (3 vials) — maximum per labeling for body weight <80 kg

Regimen	Week 1 split infusion (Day 1 / Day 2)	Weeks 2–4 (weekly) — dose (vials)	Maintenance (q3w) — dose (vials)	Covered indication / clinical note
Amivantamab-vmjw in combination with carboplatin and pemetrexed (weight-based)
Day 1: 350 mg (1 vial); Day 2: Body weight <80 kg: 1,050 mg (3 vials); Body weight ≥80 kg: 1,400 mg (4 vials)
Week 2–4 weekly: Body weight <80 kg: 1,400 mg (4 vials); Body weight ≥80 kg: 1,750 mg (5 vials)
Every 3 weeks thereafter: Body weight <80 kg: 1,750 mg (5 vials); Body weight ≥80 kg: 2,100 mg (6 vials)
NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution after progression on an EGFR tyrosine kinase inhibitor (new labeled combination indication)

Regimen / Combination	Dose schedule (initial / continuation)	Clinical context / coverage note	Coverage stance
Rybrevant (amivantamab-vmjw) + Lazcluze (lazertinib)
First-line: per labeled combination with weekly x5 (split initial infusion) then q2w maintenance; continuation allowed per NCCN for progression scenarios (asymptomatic disease, symptomatic brain lesions, or symptomatic systemic limited progression)
Added per NCCN Compendium as a continuation option; applicable for disease positive for EGFR exon 19 deletions or exon 21 L858R when used per guideline-recommended sequencing
covered

Policy Summary

PayerHealth Net

PolicyAmivantamab-vmjw (Rybrevant) for NSCLC

Policy CodePolicy CP PHAR.544

Change TypeAdded new combination indicationsdosing and criteria revisions

Effective Date09.01.21

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, oncologist involvement, mutation test results, and evidence of prior progression when required.

SourceLink

On This Page

Documentation Required

Mutation and Progression Documentation

When approval is contingent on the presence of specific EGFR mutations (e.g., EGFR exon 20 insertion, exon 19 deletions, exon 21 L858R substitutions, or other specified exons), providers must submit molecular testing results that identify the exon and specific mutation. If continuation or combination-therapy indications require prior progression on an EGFR TKI, include both the molecular test report and documentation of progression on the specified TKI.

Include molecular/genetic test reports specifying exon and mutation
If combination therapy requires prior progression on an EGFR TKI, include both mutation report and progression documentation

Denial Risk

Non‑FDA Indications and Required Evidence

For off-label or non‑FDA approved indications, include sufficient supporting evidence per the plan's off‑label use policies (CP.CPA.09 for commercial, HIM.PA.154 for HIX, CP PMN.53 for Medicaid) such as peer‑reviewed literature, clinical guidelines (e.g., NCCN), and rationale for use. Incomplete documentation may result in denial.

Follow applicable off‑label use policy and submit supporting literature/guideline references
Absence of adequate evidence or missing documentation may lead to denial