Telisotuzumab Vedotin plus Erlotinib Shows Promise in EGFR-Mutant c-MET⁺ NSCLC

Many patients diagnosed with non–small cell lung cancer (NSCLC) demonstrate overexpression of the transmembrane tyrosine kinase c-Met. The first-in-class antibody–drug conjugate targeting c-Met, telisotuzumab vedotin (Teliso-V), showed both safety and potential antitumor activity in a first-in-human study of patients with c-MET–overexpressing (c-MET⁺) NSCLC. c-MET amplification can promote resistance to EGFR inhibitors such as erlotinib, which suggests that dual targeting of c-Met and EGFR could prove to be clinically beneficial. Thus, Camidge and colleagues conducted a phase Ib clinical trial of Teliso-V in combination with erlotinib in 42 patients (36 of whom were efficacy evaluable) with advanced c-Met⁺ NSCLC. Endpoints of the study included safety, pharmacokinetics, objective response rate (ORR), and progression-free survival (PFS). Teliso-V treatment-related adverse events (AE) of any grade were observed in 37 patients (88%), with peripheral sensory neuropathy being the most frequent. Grade 3 or higher treatment-related AEs occurred in 13 patients (31%) and generally involved hypophosphatemia or peripheral sensory neuropathy. Among evaluable patients, the ORR was 30.6%, with a disease control rate (DCR) of 86.1% and a median PFS of 5.9 months. Among the 28 patients with EGFR mutations, the ORR was 32.1%, with one complete response and eight partial responses observed, the DCR was 85.7%, and the median PFS was 5.9 months. Exploratory analyses indicated that patients without EGFR^T790M mutations had an improved ORR and DCR as well as longer PFS (6.8 months) versus those with EGFR^T790M mutations (3.7 months). Additionally, an improved ORR and DCR were seen in those who had not previously received EGFR tyrosine kinase inhibitors as compared with those who did, while EGFR mutation–positive patients who had higher c-MET expression had a better ORR as compared to those who had lower c-MET expression. Overall, this trial shows that the combination of Teliso-V and erlotinib is safe and has promising antitumor activity, suggesting that additional investigation into this combination is warranted.

Camidge DR, Barlesi F, Goldman JW, Morgensztern D, Heist R, Vokes E, et al. Phase Ib study of telisotuzumab vedotin in combination with erlotinib in patients with c-Met protein–expressing non–small-cell lung cancer. J Clin Oncol 2022 Oct 26 [Epub ahead of print].

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