Abstract
The MET-targeting antibody–drug conjugate telisotuzumab vedotin (Teliso-V) is well tolerated in patients.
Major finding: The MET-targeting antibody–drug conjugate telisotuzumab vedotin (Teliso-V) is well tolerated in patients.
Concept: Teliso-V achieved partial responses in 18.8% of patients with MET-positive NSCLC in a phase I trial.
Impact: Teliso-V may be effective in MET-positive tumors, potentially including those lacking MET amplification.
The receptor tyrosine kinase MET is often aberrantly activated in solid tumors including non–small cell lung cancer (NSCLC). MET activation is associated with oncogenic transformation, therapeutic resistance, and poor prognosis. Thus, MET has emerged as a therapeutic target. An anti-MET humanized monoclonal antibody (ABT-700) has activity in patients with MET-amplified solid tumors, but not MET-overexpressing tumors without amplification. In preclinical studies, the antibody–drug conjugate telisotuzumab vedotin (Teliso-V), which links ABT-700 to the cytotoxic drug monomethyl auristatin E, has activity against MET-overexpressing tumors lacking gene amplification. These findings prompted Strickler and colleagues to assess the safety and efficacy of Teliso-V in a first-in-human phase I dose escalation and expansion study in 48 patients with solid tumors. A total of 39 patients were treated in the dose-escalation cohort, and 9 patients with MET-positive NSCLC were treated with the determined recommended phase II dose (2.7 mg/kg) in the dose-expansion phase. The primary objectives were evaluation of the safety and tolerability of Teliso-V, determination of the pharmacokinetic profile, and identification of the recommended phase II dose. Teliso-V exhibited dose-proportional antibody pharmacokinetics with a mean half-life of 2 to 4 days. Teliso-V was well tolerated, with 8 patients (17%) experiencing treatment-related grade 3–4 adverse events. In the 16 patients with MET-positive NSCLC treated with 2.4 to 3.0 mg/kg Teliso-V, 3 (18.8%) achieved a partial response, and the median progression-free survival was 5.7 months. Taken together, these results demonstrate that Teliso-V monotherapy is safe and exhibits preliminary antitumor activity in patients with MET-positive NSCLC.
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