FDA Accelerates Approval for Telisotuzumab Vedotin-tllv in NSCLC with High c-Met Overexpression

On May 14, 2025, the Food and Drug Administration (FDA) granted accelerated approval for the new therapeutic agent, telisotuzumab vedotin-tllv, marketed as Emrelis by AbbVie Inc. This innovative treatment is designed for adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that exhibits high levels of c-Met protein overexpression. Approval is contingent on patients having already undergone a prior systemic therapy, and the presence of c-Met protein overexpression must be confirmed by an FDA-approved diagnostic test.

In conjunction with Emrelis, the FDA also approved the VENTANA MET (SP44) RxDx Assay developed by Roche Diagnostics. This companion diagnostic tool is essential for identifying the c-Met protein overexpression in patients with non-squamous NSCLC, thereby determining their eligibility for Emrelis treatment.

The efficacy of Emrelis was primarily assessed through the LUMINOSITY study, a multicenter, open-label, multi-cohort clinical trial registered under NCT03539536. The trial focused on 84 patients who had previously received systemic therapy and were characterized by high c-Met protein overexpression in non-squamous NSCLC with wild-type epidermal growth factor receptor (EGFR). The study's key efficacy outcomes included the confirmed overall response rate (ORR) and the duration of response (DOR), both evaluated by a blinded independent central review in accordance with RECIST 1.1 criteria. Results indicated an ORR of 35%, with a confidence interval of 95% ranging from 24% to 46%, and a median DOR of 7.2 months, with a confidence interval of 95% stretching from 4.2 to 12 months.

Regarding safety, the most frequently reported adverse reactions in a pooled safety population included peripheral neuropathy, fatigue, decreased appetite, and peripheral edema, affecting 20% or more of the patients. Additionally, common Grade 3 or 4 laboratory abnormalities observed in at least 2% of the patients comprised decreased lymphocytes, increased glucose levels, elevated alanine aminotransferase, increased gamma-glutamyl transferase, decreased phosphorus, decreased sodium, reduced hemoglobin, and low calcium levels.

The recommended dosage for telisotuzumab vedotin-tllv is set at 1.9 mg/kg, with a maximum dose of 190 mg for patients weighing 100 kg or more. The treatment is administered as an intravenous infusion every two weeks and continues until there is either disease progression or the onset of unacceptable toxicity.

The approval process for this medication benefitted from the FDA’s Real-Time Oncology Review (RTOR) pilot program, which effectively streamlined data submissions before the comprehensive clinical application was filed. Additionally, the review was facilitated by the Assessment Aid, a voluntary submission aimed at easing the FDA’s evaluation process. Emrelis's application was granted both priority review and breakthrough designation, underscoring the significance of expedited programs for drugs and biologics targeting serious health conditions.

In summary, the FDA's decision to approve Emrelis marks a significant milestone in the treatment of non-squamous NSCLC, providing new hope for patients with limited options. The accompanying approval of the VENTANA MET (SP44) RxDx Assay further supports the personalized medicine approach, ensuring that the right patients receive this targeted therapy.