Strickler JH, et al. - Researchers undertook this first-in-human study to evaluate telisotuzumab vedotin (Teliso-V), formerly called ABBV-399, an antibody–drug conjugate of the anti–c-Met monoclonal antibody ABT-700 and monomethyl auristatin E. In patients with c-Met–positive non–small-cell lung cancer (NSCLC), outcomes yielded satisfactory safety and tolerability profiles of Teliso-V monotherapy, in addition to promising evidence of its antitumor activity.

Methods

• Researchers enrolled three to six patients with advanced solid tumors in eight cohorts (0.15 to 3.3 mg/kg) for dose escalation.
• For the dose-expansion phase, they enrolled patients with NSCLC with c-Met–overexpressing tumors (c-Met positive; immunohistochemistry membrane H-score ≥ 150).
• Teliso-V monotherapy was administered intravenously to patients on day 1 once every 3 weeks.
• Determination of safety, tolerability, pharmacokinetics, and maximum tolerated dose was performed.

Results

• Enrollment of 48 patients was done (median age, 65 years; 35.4% NSCLC; median four prior therapies).
• Dose-limiting toxicities were noted in one patient each in the 3.0-mg/kg (n = 9) and 3.3-mg/kg (n = 3) cohorts.
• On the basis of overall safety and tolerability, they defined the recommended phase II dose of 2.7 mg/kg, however, the maximum tolerated dose was not formally identified.
• Fatigue (42%), nausea (27%), constipation (27%), decreased appetite (23%), vomiting (21%), dyspnea (21%), diarrhea (19%), peripheral edema (19%), and neuropathy (17%) were identified as the most frequent treatment-emergent adverse events (any grade).
• Fatigue, anemia, neutropenia, and hypoalbuminemia (4% each) were the most frequent Teliso-V–related grade ≥ 3 adverse events.
• Approximate dose proportionality was noted for Teliso-V and total antibody pharmacokinetics, with a mean harmonic half-life of 2 to 4 days each.
• As per prospective screening, 35 (60%) of 58 patients had c-Met–positive NSCLC.
• Among the 16 patients with c-Met–positive NSCLC who were treated with Teliso-V 2.4 to 3.0 mg/kg, a partial response was noted in three (18.8%; 95% CI, 4.1% to 45.7%) (median response duration, 4.8 months; median progression-free survival, 5.7 months; 95% CI, 1.2 months to 15.4 months).
• A response was not noted in any of the other patient.