Early Trial Results With Telisotuzumab Vedotin Plus Erlotinib in c-MET–Positive Lung Cancer

By: Amy MacDonald, MS
Posted: Tuesday, February 21, 2023

c-MET is a transmembrane tyrosine kinase receptor that is overexpressed or abnormally expressed in about half of non–small cell lung cancers (NSCLCs). In normal cells, binding of hepatocyte growth factor to c-MET initiates a series of intracellular signals mediating embryogenesis and wound healing; however, tumor progression occurs in cancer cells. Telisotuzumab vedotin (also known as ABBV-399) is a first-in-class anti–c-MET antibody-drug conjugate designed to disrupt this signaling pathway. The tyrosine kinase inhibitor erlotinib inhibits transmembrane signaling via the EGFR, which is also overexpressed in NSCLC. The investigational combination therapy appears to be active in this type of lung cancer, as discussed here.

Ross Camidge MD, PhD, of the University of Colorado Cancer Center, Aurora, and colleagues presented data in the Journal of Clinical Oncology from a phase Ib study (ClinicalTrials.gov identifier NCT02099058) evaluating the combination of telisotuzumab vedotin and erlotinib in patients with NSCLC. The study enrolled 42 patients with c-MET–positive NSCLC, focusing primarily on the EGFR mutation–positive population after EGFR tyrosine kinase inhibitor treatment.

Median progression-free survival was 5.9 months (95% confidence interval = 2.8 months to not reached). Objective response rate for EGFR mutation–positive patients (n = 28) was 32.1%. Of EGFR mutation–positive patients, those who had c-MET–high disease (n = 15) had an overall response rate of 52.6%. For patients who did not have T790M-positive disease, median progression-free survival was 6.8 months, compared with 3.7 months for those who had T790M-positive disease.

As for toxicity, the most common any-grade adverse events reported were neuropathies; 24 of 42 patients (57%) experienced at least one of these events. In addition, the study authors noted, the pharmacokinetic profile of telisotuzumab vedotin plus erlotinib was similar to the antibody-drug conjugate alone.

Disclosure: For full disclosures of study authors, visit ascopubs.org.

Journal of Clinical Oncology

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