Accelerated approval is granted by the USFDA to telisotuzumab vedotin-tllv for NSCLC with high c-Met protein overexpression

On May 14, 2025, the Food and Drug Administration granted accelerated approval for telisotuzumab vedotin-tllv (Emrelis, AbbVie Inc.), a c-Met-targeted antibody and microtubule inhibitor conjugate, for adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) exhibiting high c-Met protein overexpression [≥50% of tumor cells with strong (3+) staining], as identified by an FDA-approved assay, who have undergone prior systemic therapy.

The FDA has approved the VENTANA MET (SP44) RxDx Assay (Roche Diagnostics) as a companion diagnostic test to assist in identifying c-Met protein overexpression in individuals with non-squamous NSCLC who may qualify for therapy with Emrelis.

The efficacy was assessed in the LUMINOSITY research (NCT03539536), a multicenter, open-label, multi-cohort investigation. The trial comprised 84 patients with epidermal growth factor receptor (EGFR) wild-type, non-squamous non-small cell lung cancer (NSCLC) exhibiting significant c-Met protein overexpression, all of whom had undergone prior systemic therapy.

The primary efficacy outcome measures were the overall response rate (ORR) and duration of response (DOR), assessed by blinded independent central review (BICR) in accordance with RECIST 1.1. The overall response rate (ORR) was 35% (95% confidence interval: 24, 46), and the median duration of response (DOR) was 7.2 months (95% confidence interval: 4.2, 12).

In a consolidated safety cohort, the predominant adverse events (≥20%) included peripheral neuropathy, tiredness, diminished appetite, and peripheral edema. The prevalent Grade 3 or 4 laboratory abnormalities (≥2%) included reduced lymphocytes, elevated glucose, increased alanine aminotransferase, heightened gamma glutamyl transferase, diminished phosphorus, decreased sodium, lowered hemoglobin, and decreased calcium.

The advised dosage of telisotuzumab vedotin-tllv is 1.9 mg/kg (capped at 190 mg for patients weighing ≥100 kg), administered as an intravenous infusion biweekly, unless disease progression or intolerable toxicity occurs.