Dr Strickler on the Development of Telisotuzumab Adizutecan in MET-Amplified Gastric Cancer

“We know that c-Met overexpression is common in many gastroesophageal cancers. Because this appears to be a relevant target, it would be natural to consider an antibody-drug conjugate that can use that c-Met expression as an entry point into the cell, thereby delivering that toxic payload.”

John H. Strickler, MD, associate professor, medicine, Division of Medical Oncology, associate director, Clinical Research, Gastrointestinal Oncology, Duke Cancer Institute Molecular Tumor Board, Duke University, discusses the rationale for developing telisotuzumab adizutecan (ABBV-400) for the treatment of patients with MET gene–amplified advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Telisotuzumab adizutecan is an antibody-drug conjugate (ADC) comprising an antibody targeting c-Met with a topoisomerase I inhibitor payload, Strickler begins. The agent is optimized for efficient cellular uptake and delivery of cytotoxic chemotherapy to c-Met–expressing cells, he reports. This ADC is designed to leverage c-Met overexpression, which is common in many gastroesophageal cancers, as an entry point to deliver its potent payload, Strickler explains. Given the significant unmet need for patients with this disease entity, which is marked by short survival times despite available treatments, novel therapeutic approaches such as telisotuzumab adizutecan could improve outcomes, Strickler says.

In a phase 1, first-in-human study (NCT05029882), telisotuzumab adizutecan was evaluated in patients with advanced solid tumors, including those with advanced gastric or GEJ adenocarcinoma (n = 42). These patients were heavily pretreated, having received at least 1 or 2 prior lines of therapy. Findings presented at the 2024 ESMO Congress demonstrated an objective response rate of 28.6% (95% CI, 15.7%-44.6%), including 1 complete response and 11 partial responses. Furthermore, the median progression-free survival was 4.0 months (95% CI, 2.76-4.86). These results compare favorably with data observed with the current standard of care, highlighting the potential of telisotuzumab adizutecan as a valuable treatment option in this patient population, Strickler concluded.