On May 14, the U.S. Food and Drug Administration (FDA) granted accelerated approval to telisotuzumab vedotin-tllv (Emrelis), a c-Met–directed antibody and microtubule inhibitor conjugate, for adults with locally advanced or metastatic, nonsquamous, 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 also approved the VENTANA MET (SP44) RxDx Assay (Roche Diagnostics) as a companion diagnostic test to aid in detecting c-Met protein overexpression in patients with nonsquamous NSCLC who may be eligible for treatment with telisotuzumab vedotin.
LUMINOSITY
Telisotuzumab vedotin’s efficacy was evaluated in the LUMINOSITY study (ClinicalTrials.gov identifier NCT03539536), a multicenter, open-label, multicohort trial. The trial included 84 patients with EGFR wild-type, nonsquamous NSCLC with high c-Met protein overexpression who had received prior systemic therapy.
The major efficacy outcome measures were confirmed overall response rate and duration of response determined by blinded independent central review according to Response Evaluation Criteria in Solid Tumors version 1.1. The overall response rate was 35% (95% confidence interval [CI] = 24%–46%) and median duration of response was 7.2 months (95% CI = 4.2–12 months).
In a pooled safety population, the most common adverse reactions (occurring in ≥ 20% of patients) were peripheral neuropathy, fatigue, decreased appetite, and peripheral edema. The most common grade 3 or 4 laboratory abnormalities (occurring in ≥ 2%) were decreased lymphocytes, increased glucose, increased alanine aminotransferase, increased gamma glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin, and decreased calcium.
The recommended telisotuzumab vedotin dose is 1.9 mg/kg (up to a maximum of 190 mg for patients weighing ≥100 kg) as an intravenous infusion every 2 weeks until disease progression or unacceptable toxicity.
This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review and Breakthrough Therapy designation.
