FDA Approves New Antibody–Drug Conjugate for Non-Squamous Non–Small Cell Lung Cancer with c-Met Overexpression

On May 14, 2025, the U.S. Food and Drug Administration (FDA) granted accelerated approval to telisotuzumab vedotin, an antibody–drug conjugate (ADC), for the treatment of adult patients with locally advanced or metastatic non-squamous non–small cell lung cancer (NSCLC) with c-Met overexpression—defined as ≥50% of tumor cells showing strong (3+) staining by immunohistochemistry—who have received at least one prior line of systemic therapy.

The approval was based on results from the LUMINOSITY trial, a multicenter, open-label, multi-cohort study that enrolled 84 previously treated patients with non-squamous, EGFR wild-type NSCLC and high c-Met expression. The objective response rate (ORR) was 35% (95% CI: 24–46), with a median duration of response (DOR) of 7.2 months (95% CI: 4.2–12).

In the pooled safety population, the most commonly reported adverse events (occurring in ≥20% of patients) included peripheral neuropathy, fatigue, decreased appetite, and peripheral edema. The most frequent grade ≥3 laboratory abnormalities (occurring in at least 2% of patients) were lymphopenia, hyperglycemia, elevations in alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), as well as low levels of phosphorus (hypophosphatemia), sodium (hyponatremia), calcium (hypocalcemia), and anemia.

The recommended dosage is 1.9 mg/kg (maximum dose of 190 mg for patients ≥100 kg), administered via intravenous infusion every two weeks, until disease progression or unacceptable toxicity.

The accelerated approval of telisotuzumab vedotin marks an important advancement in the treatment of non-squamous NSCLC with c-Met overexpression, offering a targeted therapeutic option. The FDA's decision further underscores the growing role of precision oncology in the management of lung cancer.

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