CurrentAnthemPolicy CC-0201

Rybrevant (amivantamab-vmjw) for NSCLC

Clinical criteria governing medical-benefit coverage and prior authorization for Rybrevant (amivantamab-vmjw) in adults with locally advanced or metastatic non-small cell lung cancer (NSCLC), including use combinations with lazertinib or carboplatin-pemetrexed and single-agent use for EGFR exon 20 insertion mutations.

Policy Summary

PayerAnthem

PolicyRybrevant (amivantamab-vmjw) for NSCLC

Policy CodePolicy CC-0201

Change TypeRevised (includes additions and removals)

Effective Date10/01/2025

Next Review Date

Key ActionObtain prior authorization with documentation of EGFR mutation status, line of therapy, and prior treatments to support Rybrevant use.

SourceLink

POLICY UPDATE CHANGES

Add use in NSCLC with brain metastases per NCCN and added ICD-10-CM C79.31.

Remove select exon 21 mutations from subsequent therapy indication per NCCN and label; updated HCPCS description for J9061.

Add new FDA indication for continuation of therapy following disease progression on Rybrevant and lazertinib.

J9061HCPCS code for Rybrevant (per document)

EGFR exon 20Key mutation

Brain metastasesUpdated inclusion

CC-0201Internal id

Coverage Criteria for Rybrevant (amivantamab-vmjw)

Policy Summary

PayerAnthem

PolicyRybrevant (amivantamab-vmjw) for NSCLC

Policy CodePolicy CC-0201

Change TypeRevised (includes additions and removals)

Effective Date10/01/2025

Next Review Date

Key ActionObtain prior authorization with documentation of EGFR mutation status, line of therapy, and prior treatments to support Rybrevant use.

SourceLink

On This Page

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Covered Indications / Criteria

Requests for Rybrevant (amivantamab-vmjw) may be approved if ONE of the following distinct criteria pathways is met:

Pathway A - Single-agent for EGFR exon 20 insertion: I. Diagnosis of recurrent, advanced or metastatic Non-small Cell Lung Cancer (NSCLC); II. Tumor harbors EGFR exon 20 insertion mutation; III. Disease progression on or after platinum-based chemotherapy; IV. Has not progressed on prior therapy with Rybrevant; V. Using Rybrevant as a single agent.

Supports single-agent approval for EGFR exon 20 insertion after platinum-based chemotherapy.

Pathway B - First-line combination for EGFR exon 20 insertion: I. Diagnosis of locally advanced or metastatic NSCLC; II. Tumor harbors EGFR exon 20 insertion mutation; III. Using Rybrevant as first-line therapy in combination with carboplatin and pemetrexed.

First-line combination option for EGFR exon 20 insertion.

Pathway C - Subsequent therapy for EGFR exon 19 deletion or exon 21 L858R: I. Diagnosis of recurrent, advanced, or metastatic NSCLC; II. Tumor harbors EGFR exon 19 deletion or exon 21 L858R mutation; III. Using Rybrevant in combination with carboplatin and pemetrexed as subsequent therapy; IV. Disease progression on an EGFR tyrosine kinase inhibitor (e.g., osimertinib).

Subsequent therapy after progression on an EGFR TKI.

Pathway D - Lazertinib combinations and continuation: I. Diagnosis of locally advanced or metastatic NSCLC; II. Tumor harbors EGFR exon 19 deletion or exon 21 L858R substitution mutation; AND (A) Using Rybrevant as first-line therapy in combination with lazertinib OR (B) Using Rybrevant as continuation of therapy following disease progression on Rybrevant and lazertinib.

Includes first-line combination with lazertinib and FDA-listed continuation after progression on Rybrevant + lazertinib.

Pathway E - NSCLC with brain metastases (NCCN 2A): I. Diagnosis of central nervous system cancer consistent with brain metastases from primary NSCLC (NCCN 2A); II. Primary NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutation; III. Using Rybrevant in combination with lazertinib OR using Rybrevant in combination with carboplatin and pemetrexed.

NCCN-supported use in NSCLC with brain metastases included in policy.

Requests for Rybrevant (amivantamab-vmjw) may not be approved if the above criteria are not met and for all indications not included above.

Any use outside the listed criteria pathways (including indications not described in the criteria) is not approved per this document.

Regimens and Permitted Combinations

Regimen	Indication / Key Criteria	Coverage
Rybrevant in combination with lazertinib
First‑line treatment of locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations (FDA‑approved); NCCN includes use for NSCLC with brain metastases.
Covered
Rybrevant in combination with carboplatin + pemetrexed
Two settings: 1) First‑line treatment of locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations (FDA‑approved); 2) Treatment of locally advanced or metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations whose disease has progressed on or after an EGFR tyrosine kinase inhibitor (e.g., osimertinib).
Covered

Regimen	Indication / Key Criteria	Coverage
Rybrevant (single agent)
Treatment of recurrent, advanced, or metastatic NSCLC with EGFR exon 20 insertion mutations after disease progression on or after platinum‑based chemotherapy; patient has not progressed on prior Rybrevant therapy.
Covered

Regimen	Indication / Key Criteria	Coverage
Rybrevant + carboplatin + pemetrexed
Use for locally advanced or metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations in combination with carboplatin and pemetrexed after disease progression on an EGFR tyrosine kinase inhibitor (e.g., osimertinib).
Covered with criteria

Coding and Diagnosis

HCPCSHCPCS

J9061

Injection, amivantamab-vmjw, 2 mg [Rybrevant]

ICD-10 DiagnosisICD-10

C33	Malignant neoplasm of trachea
C34.00-C34.92	Malignant neoplasm of bronchus and lung
C79.31	Secondary malignant neoplasm of brain

Prior progression on platinum-based chemotherapy — requirement for single-agent use

RequirementDisease progression on or after platinum-based chemotherapy is required for single-agent Rybrevant when treating NSCLC with EGFR exon 20 insertion mutations.

Applicable indicationSingle-agent use for locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations (Pathway A).

Documentation to provideClinical record showing prior platinum-based chemotherapy and subsequent radiographic or clinical evidence of disease progression after that therapy.

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization required with documentation that the member meets the policy clinical criteria (mutation status, line of therapy, prior therapies) before therapy is initiated.

Prior authorization is required for Rybrevant (amivantamab-vmjw).
Requests must include documentation of EGFR mutation testing confirming the specific exon mutation (e.g., exon 20 insertion, exon 19 deletion, or exon 21 L858R) as applicable to the requested indication.

Step Therapy

Prior Therapy Expectations

Policy expects prior exposure to specified therapies in certain indications. Provide documentation of prior lines of therapy and disease progression where required.

For NSCLC with EGFR exon 20 insertion mutations: documentation that disease progressed on or after platinum-based chemotherapy is required.
For requests that require prior EGFR TKI exposure (e.g., osimertinib): documentation of disease progression on that EGFR TKI must be provided.
For indications where Rybrevant is used in combination as first-line therapy (e.g., with carboplatin and pemetrexed or with lazertinib), document intent for first-line combination use per criteria.

Documentation Required

Include relevant diagnosis and treatment history supporting the requested use of Rybrevant (amivantamab-vmjw).

Relevant diagnosis (NSCLC histology, stage/extent, presence of brain metastases if applicable).
EGFR mutation testing results specifying exon and mutation type.
Prior systemic therapy details (agents, dates, reason for discontinuation/progression), including platinum-based chemotherapy and prior EGFR TKIs where applicable.
Planned regimen details if requesting combination therapy (e.g., carboplatin + pemetrexed, lazertinib).

Denial Risk

Denial Conditions

Requests may not be approved if the specified clinical criteria are not met and for all indications not included in the listed criteria.

Requests lacking confirmation of the required EGFR mutation type for the indication will be denied.
Requests without documentation of required prior therapies or progression where specified will not be approved.
Use of Rybrevant for indications outside those explicitly listed in the policy is not approved.

Line of Therapy Criteria

First-line

First-line: Use Rybrevant as first-line therapy in combination with carboplatin and pemetrexed for locally advanced or metastatic NSCLC with EGFR exon 20 insertion OR use Rybrevant as first-line therapy in combination with lazertinib for locally advanced or metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution.

First-line combination regimens per FDA/NCCN.

Second-line

Second-line / Subsequent therapy: Use Rybrevant in combination with carboplatin and pemetrexed for recurrent, advanced, or metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R mutation after disease progression on an EGFR tyrosine kinase inhibitor (e.g., osimertinib); OR use Rybrevant as single agent for NSCLC with EGFR exon 20 insertion after disease progression on or after platinum-based chemotherapy (provided the member has not progressed on prior Rybrevant).

Requires prior progression on specified prior therapies per regimen.

Salvage

Salvage / Continuation following progression: Continuation of therapy following disease progression on Rybrevant and lazertinib is an FDA-listed indication and is included in this policy as a salvage/continuation pathway.

Document history: FDA indication added 11/15/2024; policy updated to reflect continuation following progression.

Biomarker and Mutation Requirements

EGFR exon 20 insertion — biomarker requirement details

Required biomarkerEGFR exon 20 insertion mutation is required for approvals involving Rybrevant single-agent use and for some first-line combination regimens.

Indications listedSingle-agent treatment for adults with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations; first-line combination with carboplatin and pemetrexed for EGFR exon 20 insertion.

Source guidanceNCCN recommendations align with FDA indications and include use in NSCLC with brain metastases.

EGFR exon 19 deletion or exon 21 L858R substitution — biomarker requirement details

Required biomarkerEGFR exon 19 deletion or exon 21 L858R substitution mutation is required for Rybrevant use in combination with lazertinib and for certain carboplatin+pemetrexed combinations.

Indications listedFirst-line combination with lazertinib for locally advanced or metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R; combination with carboplatin and pemetrexed for disease progressed on an EGFR TKI.

Brain metastasesNCCN-supported use in NSCLC metastasized to the brain with these mutations when using Rybrevant plus lazertinib or plus carboplatin+pemetrexed.

Background

Rybrevant is a bispecific antibody directed at the epidermal growth factor receptor (EGFR) and MET receptors indicated for subsets of adults with locally advanced or metastatic non‑small cell lung cancer (NSCLC). FDA- and guideline-supported uses covered by this policy include single‑agent therapy for EGFR exon 20 insertion mutations and combination regimens with lazertinib or carboplatin plus pemetrexed for EGFR exon 19 deletions or exon 21 L858R substitutions; NCCN guidance also supports use for NSCLC with brain metastases. Prior authorization is required and approval is contingent on meeting the specific clinical criteria (mutation status, line of therapy, prior treatments) described in this policy.

Definitions

First-line therapy — definition

DefinitionFirst-line therapy: the first or primary treatment for the diagnosis, which may include surgery, chemotherapy, radiation therapy, or combinations of these.

Policy contextUsed in document to denote initial therapy settings such as Rybrevant plus lazertinib or plus carboplatin+pemetrexed when indicated as first-line for specified EGFR mutations.

ExamplesFirst-line combination: Rybrevant with lazertinib for EGFR exon 19/21; Rybrevant with carboplatin and pemetrexed for EGFR exon 20 insertion (first-line option).

Progressive Disease (PD) — definition

DefinitionProgressive Disease (PD): cancer that is growing, spreading, or getting worse.

Policy usePD is used as a threshold for coverage decisions, e.g., ‘disease progression on or after platinum-based chemotherapy’ for single-agent Rybrevant in EGFR exon 20 insertion.

Implication for prior therapyDocumentation of progression (radiographic or clinical) following prior therapy is required where specified in the criteria pathways.

Document Revision History

2025-08-15select_reviewLatest

Added use in NSCLC with brain metastases per NCCN and added ICD-10-CM C79.31 to coding.

2025-05-16annual_review

Removed select exon 21 mutations from subsequent therapy indication per NCCN and label; updated HCPCS J9061 description.

2024-11-15select_review

Added FDA indication for continuation of therapy following disease progression on Rybrevant and lazertinib.

2024-09-09select_review

Added new indication as first-line therapy in combination with lazertinib and updated ICD-10 coding for C33 and C34 ranges.

2024-05-17annual_review

Added use as subsequent therapy after progression on osimertinib for NSCLC with exon 19 deletion or certain exon 21 mutations; added recurrent disease to first-line use.

2024-03-11select_review

Added new FDA approved indication for first-line therapy of NSCLC.

2023-05-19annual_review

Minor wording and formatting updates.

2022-05-20annual_review

Updated criteria to include recurrent disease and no prior progression on Rybrevant per NCCN; ICD-10 coding additions and revisions applied.

2021-06-14annual_review

Initial clinical criteria document for Rybrevant created and HCPCS/ICD-10 coding established (later revised to J9061 and C34 codes).