Telisotuzumab Vedotin-tllv (Emrelis)

Number: 1085

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses telisotuzumab vedotin-tllv (Emrelis) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of telisotuzumab vedotin-tllv (Emrelis) is required of all Aetna participating providers and members in applicable plan designs. For precertification of telisotuzumab vedotin-tllv (Emrelis), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

1. Criteria for Initial Approval

   Non-Small Cell Lung Cancer (NSCLC)

   Aetna considers telisotuzumab vedotin-tllv (Emrelis) medically necessary for subsequent treatment of locally advanced, recurrent, or metastatic non-squamous NSCLC with high c-Met protein overexpression [greater than or equal to 50% of tumor cells with strong (3+) staining], and EGFR wild-type, as a single agent.

   Aetna considers all other indications as experimental, investigational, or unproven.

2. Continuation of Therapy

   Aetna considers continuation of telisotuzumab vedotin-tllv (Emrelis) therapy medically necessary in members requesting reauthorization for an indication listed in the Criteria for Initial Approval section when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Telisotuzumab vedotin-tllv is supplied as Emrelis 20 mg or 100 mg lyophilized powder in a single-dose vial injection for intravenous infusion only.

• The recommended dosage of Emrelis is 1.9 mg/kg administered intravenously over 30 minutes every 2 weeks until disease progression or unaccpetable toxicity.
• Reconstitute and further dilute Emrelis prior to intravenous infusion.

Source: AbbVie, 2025

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
HCPCS codes covered if selection criteria are met:
J9326	Injection, telisotuzumab vedotin-tllv, 1 mg
Other CPT codes related to the CPB:
81235	EGFR (epidermal growth factor receptor) (eg, non-small cell lung cancer) gene analysis, common variants (eg, exon 19 LREA deletion, L858R, T790M, G719A, G719S, L861Q)
96401 - 96548	Chemotherapy and other highly complex drug or highly complex biologic agent administration
ICD-10 codes covered if selection criteria are met:
C34.00 - C34.92	Malignant neoplasm of bronchus and lung

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Emrelis is indicated for the treatment of adult patients with locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression [greater than or equal to 50% of tumor cells with strong (3+) staining], as determined by an FDA-approved test, who have received a prior systemic therapy.

Compendial Uses

• Non-Small Cell Lung Cancer - recurrent

Telisotuzumab vedotin-tllv is available as Emrelis (AbbVie Inc.), a c-Met-directed antibody drug conjugate (ADC) made up of a humanized immunoglobulin G1 kappa (IgGk) monoclonal antibody conjugated to the small molecule microtubule-disrupting agent, monomethyl auristatin E (MMAE), via a protease-cleavable valine-citrulline (vc) linker. The is manufactured in a mammalian cell line (Chinese hamster ovary) and the drug-linker is manufactured by chemical synthesis (AbbVie, 2025).

The antibody is a humanized IgG kappa (IgGk) directed against c-Met, the cell surface receptor for hepatocyte growth factor. After binding to c-Met-expressing cells, Emrelis undergoes internalization and intracellular cleavage of MMAE. MMAE interferes with the microtubule network of actively dividing cells, subsequently inducing cell cycle arrest and apoptotic cell death. Emrelis showed antitumor activity in xenograft models of non-small cell lung cancer (NSCLC) (AbbVie, 2025).

According to the prescribing information, Emrelis carries the following warnings and precautions and adverse reactions:

Warnings and precautions

• Peripheral neuropathy: Monitor patients for new or worsening peripheral neuropathy. Withhold, reduce the dose, or permanently discontinue Emrelis based on the severity.
• Interstitial lung disease (ILD)/pneumonitis: Severe, life-threatening or fatal ILD/pneumonitis may occur. Withhold or permanently discontinue Emrelis based on the severity.
• Ocular surface disorders: Monitor patients for signs or symptoms of ocular surface disorders, including vision changes. Withhold or permanently discontinue Emrelis based on the severity.
• Infusion-related reactions (IRR): Monitor patients for IRR. Withhold, reduce the rate of infusion, or permanently discontinue Emrelis based on the severity. For patients who experience IRR, administer premedications prior to subsequent infusions.
• Embryo-fetal toxicity: Can cause fetal harm. Advise patients about the potential risk to a fetus and to use effective contraception.

On May 14, 2025, the U.S. Food and Drug Administration granted accelerated approval to telisotuzumab vedotin-tllv (Emrelis) a c-Met-directed antibody and microtubule inhibitor conjugate, for adults with locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression [≥50% of tumor cells with strong (3+) staining], as determined by an FDA-approved test, who have received a prior systemic therapy. The FDA approval was based on supporting data from the LUMINOSITY study (FDA, 2025).

In the LUMINOSITY study, multicenter, open-label, single-arm, multi-cohort clinical trial, investigators evaluated the efficacy of telisotuzumab vedotin-tllv (Emrelis). Patients were eligible for the study if the had locally advanced or metastatic NSCLC with c-Met protein overexpression and treatment with prior systemic therapy (including no more than one line of prior chemotherapy) in the locally advanced or metastatic setting. Patients were excluded if they had received and/or had a history of interstitial lung disease (ILD) pneumonitis treatment with steroids or ILD/pneumonitis within 3 months of the first dose (AbbVie, 2025; FDA, 2025).

Patients received Emrelis 1.9 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity. The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by a blinded independent central review (BICR) (AbbVie, 2025; FDA, 2025).

The efficacy population included 84 patients with non-squamous, EGFR wild-type NSCLC with high c-Met protein overexpression who had received prior systemic therapy. High c-Met protein overexpression was established as ≥ 50% of tumor cells with strong (3+) membrane staining (AbbVie, 2025; FDA 2025).

The ORR was 35% (95% Confidence Interval [CI]: 24, 46) and median DOR was 7.2 months (95% CI: 4.2, 12) (AbbVie, 2025; FDA, 2025).

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References