A first-in-human study evaluated Telisotuzumab Vedotin (Teliso-V), an antibody-drug conjugate targeting c-Met-positive tumors, particularly in non-small-cell lung cancer (NSCLC) patients. The study enrolled 48 patients, with a median age of 65 years, who had advanced solid tumors, including 35.4% with NSCLC. Patients received Teliso-V intravenously every three weeks. The study aimed to determine the safety, tolerability, pharmacokinetics, and maximum tolerated dose of Teliso-V.
Dose-limiting toxicities were observed in one patient each in the 3.0-mg/kg and 3.3-mg/kg cohorts. Although the maximum tolerated dose was not formally identified, the recommended phase II dose was set at 2.7 mg/kg based on overall safety and tolerability. Common treatment-emergent adverse events included fatigue, nausea, constipation, decreased appetite, vomiting, dyspnea, diarrhea, peripheral edema, and neuropathy. Grade ≥3 adverse events related to Teliso-V were fatigue, anemia, neutropenia, and hypoalbuminemia.
Pharmacokinetic analysis showed that Teliso-V and total antibody pharmacokinetics were approximately dose proportional, with a mean harmonic half-life of 2 to 4 days. Prospective screening identified 35 out of 58 patients with c-Met-positive NSCLC. Among 16 c-Met-positive NSCLC patients treated with Teliso-V doses of 2.4 to 3.0 mg/kg, three achieved a partial response, with a median response duration of 4.8 months and a median progression-free survival of 5.7 months. No other patients experienced a response, indicating Teliso-V's potential efficacy in a subset of c-Met-positive NSCLC patients.
