Telisotuzumab adizutecan for metastatic colorectal cancer: a c-MET-targeted antibody-drug conjugate with a topoisomerase inhibitor payload.

Abstract

Introduction: Metastatic colorectal cancer (mCRC) remains a disease of significant unmet need, particularly for patients with refractory disease and limited targeted treatment. However, c-MET protein overexpression, which has been associated with poor prognosis, represents an emerging therapeutic target. Telisotuzumab adizutecan (Temab-A) is a novel antibody-drug conjugate designed to deliver a potent topoisomerase 1 inhibitor payload to c-MET-expressing tumor cells.

Areas covered: This review summarizes the pharmacology, clinical efficacy, and safety of Temab-A in mCRC. In a phase 1 study, 122 heavily pretreated patients with mCRC showed an objective response rate (ORR) of 15.6%; in an exploratory post-hoc subgroup (n = 25) with high c-MET expression treated at doses ≥2.4 mg/kg, ORR was 36.0%. In a phase 1 dose-optimization cohort (n = 30 at the recommended phase 2 dose), Temab-A plus bevacizumab showed an ORR of 30% and median progression-free survival of 6.8 months in an unselected population.

Expert opinion: By exploiting c-MET surface expression rather than signaling dependency, Temab-A provided preliminary clinical activity across a broad population, including a clinically meaningful subgroup with c-MET overexpression. The ongoing phase 3 AndroMETa-CRC-560 trial will determine whether Temab-A plus bevacizumab can become a new therapeutic option for mCRC.