Emrelis for c-Met Positive NSCLC: A Breakthrough in Antibody-Drug Conjugate-based Treatment Approved by the FDA

Abstract: Telisotuzumab Vedotin (Teliso-V), previously known as ABBV-399, is a novel, first-in-class antibodydrug conjugate developed by AbbVie. It combines an anti-c-Met monoclonal antibody (ABT-700) with monomethyl auristatin E (MMAE), a potent microtubule-disrupting agent, via a cleavable linker. This design allows selective delivery of the cytotoxic payload to c-Met-overexpressing tumour cells, thereby bypassing reliance on MET signalling for efficacy. Preclinical studies demonstrated that ABBV-399 effectively inhibited the growth of xenograft tumors refractory to other MET-targeted inhibitors. In early Phase I trials, the agent showed a favourable safety profile and elicited objective tumour responses in c-Met-expressing non-small cell lung cancer (NSCLC) patients. In the Phase II LUMINOSITY study, which served as the basis for accelerated FDA approval, Teliso-V demonstrated an overall response rate (ORR) of 35% and a median duration of response (DOR) of 9 months in patients with high c-Met protein overexpression. Continued approval may depend on confirmatory Phase III data.