Medical Drug Criteria (MDC)

MDC Num:       P1.001.008
MDC Name:     RYBREVANT^® (amivantamab-vmjw) 
MDC ID:          [P1.001.008] [Ac /L / M+ / P+ ]

Last Review:       September 22, 2025
Next Review:      September 20, 2025
 

Related MDC: NONE

RYBREVANT^® (amivantamab-vmjw) 

Summary

Rybrevant (amivantamab-vmjw) is a bispecific EGF receptor-directed and MET receptor-directed antibody indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring:
 
EGFR exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy, OR
 
EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test, in combination with chemotherapy or lazertinib.

OBJECTIVE

To define the medically necessary use of Rybrevant in adult patients with locally advanced or metastatic NSCLC harboring EGFR mutations, consistent with FDA labeling and NCCN guidelines.

POLICY STATEMENT

Rybrevant may be considered medically necessary for adults (≥18 years) with advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations, or EGFR exon 19 deletions/L858R substitution mutations, meeting the criteria outlined in this document.

POLICY GUIDELINES

Coverage eligibility will be considered when:

NSCLC confirmed with EGFR exon 20 insertion mutation (progressed after platinum chemotherapy).

NSCLC confirmed with EGFR exon 19 deletion or exon 21 L858R mutation detected by FDA-approved test, used in combination with chemotherapy or lazertinib.

Authorization up to 12 months.

DOSAGE/ADMINISTRATION:

The recommended dosage of RYBREVANT is based on baseline body weight and administered as an intravenous infusion after dilution.

• Administer premedications as recommended.

• Administer via a peripheral line on Week 1 and Week 2.

• Administer RYBREVANT in combination with chemotherapy weekly for 4 weeks, with the initial dose as a split infusion in Week 1 on Day 1 and Day 2, then administer every 3 weeks starting at Week 7. 

• Administer RYBREVANT in combination with lazertinib or RYBREVANT as a single agent weekly for 5 weeks, with the initial dose as a split infusion in Week 1 on Day 1 and Day 2, then administer every 2 weeks starting at Week 7. 

• When administering RYBREVANT in combination with lazertinib, administer anticoagulant prophylaxis to prevent venous thromboembolic (VTE) events for the first four months of treatment.

• Administer diluted RYBREVANT intravenously according to the infusion rates in Table

REQUIRED MEDICAL INFORMATION

Initiation of amivantamab-vmjw (Rybrevant) meets the definition of medical necessity for any of the following indications when all associated criteria is met:

1. Non-Small Cell Lung Cancer (NSCLC)
   • Member is diagnosed with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations –laboratory documentation of mutation must be submitted
   • Amivantamab is used as subsequent therapy (not first-line).
   • Amivantamab is used as a single agent.
   • Amivantamab is administered weekly for 4 weeks, then every 2 weeks starting at week 5.
   • Dose does not exceed:
     • Weight less than 80 kg: 1050 mg (3 vials)
     • Weight greater than or equal to 80 kg: 1400 mg (4 vials)
2. Member has another FDA-approved or NCCN-supported diagnosis, and BOTH of the following criteria are met:
   • EITHER of the following:
     • Member is diagnosed with a condition that is consistent with an indication listed in the product’s FDA-approved prescribing information (or package insert) AND member meets any additional requirements listed in the “Indications and Usage” section of the FDA-approved prescribing information (or package insert).
     • Indication AND usage is recognized in NCCN Drugs and Biologics Compendium as a Category 1 or 2A recommendation.
   • Dosage does not exceed the maximum recommended in the FDA-approved prescribing information or the maximum recommended by the applicable NCCN guidelines for the diagnosis.

Continuation of amivantamab-vmjw (Rybrevant) meets the definition of medical necessity when ALL of the following criteria are met:

1. Authorization/reauthorization has been previously approved by Triple-S or another health plan in the past two years for treatment of NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, or other FDA-approved or NCCN supported diagnosis, OR the member has previously met all indication-specific criteria.
2. Member’s disease has not progressed on treatment with amivantamab.
3. Amivantamab is administered every 2 weeks.
4. Dose does not exceed:
   • Weight less than 80 kg: 1050 mg (3 vials)
   • Weight greater than or equal to 80 kg: 1400 mg (4 vials)

EXCLUSION CRITERIA

None specified.

BENEFIT APPLICATION

BlueCard/National Account Issues: 

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

BACKGROUND

Amivantamab is a fully human bispecific IgG1 antibody targeting EGFR and MET.
 
FDA accelerated approval: May 21, 2021, for EGFR exon 20 insertions post-platinum chemotherapy.
 
Expanded approval in 2024 for exon 19 deletions/L858R in combination with chemotherapy or lazertinib.
 
Clinical efficacy supported by CHRYSALIS and PAPILLON trials, showing durable responses and improved PFS compared to chemotherapy alone.

REGULATORY STATUS

FDA-approved indications: EGFR exon 20 insertions (post-platinum), EGFR exon 19 deletions/L858R (with chemo or lazertinib).
 
NCCN Guidelines (NSCLC v.3.2023): Category 1/2A recommendation for these populations.

OTHER CRITERIA

Validate that the treatment regimen is following the most up to date NCCN guidelines recommendations.

RATIONAL

Rybrevant provides a novel mechanism targeting both EGFR and MET, addressing resistance pathways. Clinical studies confirm its efficacy in a difficult-to-treat population with limited alternatives.

PRACTICE GUIDELINES AND POSITION STATEMENTS

NCCN NSCLC Guidelines (2023–2025): Recommends Rybrevant in combination with chemotherapy or lazertinib for exon 19 deletions/L858R; and as monotherapy for exon 20 insertions after platinum therapy.

MEDICARE NATIONAL COVERAGE

No National Coverage Determination (NCD). Coverage typically at the discretion of local contractors.

References

 
1. Florida Blue Medical Coverage Guidelines. mcgs.bcbsfl.com
 
 
2. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 3.2023. nccn.org
 
 
3. Rybrevant (amivantamab-vmjw) Prescribing Information. Janssen Biotech, Inc. Revised 08/2024.
 
 
4. Park K, et al. Amivantamab plus lazertinib in EGFR-mutant NSCLC (CHRYSALIS). J Clin Oncol. 2021.
 
 
5. Johnson M, et al. Amivantamab with chemotherapy in EGFR exon 19 deletions/L858R (PAPILLON). NEJM. 2023.

Codes

Applicable Modifiers

N/A

Policy History