Activity of Antibody-Drug Conjugate Telisotuzumab Vedotin in c-Met–Positive Advanced NSCLC
In a phase I study reported in the Journal of Clinical Oncology, Strickler et al found evidence of activity of the antibody-drug conjugate telisotuzumab vedotin in non–small cell lung cancer (NSCLC) overexpressing c-Met. The agent combines the anti–c-Met monoclonal antibody telisotuzumab with the cytotoxic antimicrotubule agent monomethyl auristatin E.
Study Details
A total of 48 patients were enrolled, including 39 with advanced solid tumors in the dose-escalation phase and 9 with c-Met–positive NSCLC in the dose-expansion phase (median = 4 prior treatments). Overall, the study population included 16 patients with c-Met–positive NSCLC (median = 3 prior treatments for metastatic disease). Patients received doses ranging from 0.15 to 3.3 mg/kg intravenously every 3 weeks.
Toxicity
One patient each in the 3.0-mg/kg (n = 9) and 3.3-mg/kg (n = 3) groups experienced dose-limiting toxicities. The maximum tolerated dose was not identified, with a dose of 2.7 mg/kg being selected as the phase II dose on the basis of overall safety and tolerability. The most common adverse events of any grade were fatigue (42%), nausea (27%), constipation (27%), decreased appetite (23%), vomiting (21%), dyspnea (21%), diarrhea (19%), peripheral edema (19%), and neuropathy (17%). The most common treatment-related grade ≥ 3 adverse events were fatigue, anemia, neutropenia, and hypoalbuminemia (4% each).
Responses in NSCLC
Among the 16 patients with c-Met–positive NSCLC, partial response was observed in 3 (18.8%). In the 3 responders, durations of response were 3.1, 4.8, and 11.1 months, and progression-free survival was 5.7, 6.0, and 15.4 months. An additional 6 patients (38%) had stable disease. Median progression-free survival among all 16 patients was 5.7 months (95% confidence interval [CI] = 1.2–15.4 months). No other patients had a response to treatment.
The investigators concluded, “[Telisotuzumab vedotin] monotherapy demonstrated favorable safety and tolerability profiles, with encouraging evidence of antitumor activity in patients with c-Met–positive NSCLC.”
The study was supported by AbbVie Inc.
John H. Strickler, MD, of Duke Cancer Institute, Duke University Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
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