Dr Strickler on the Rationale for Evaluating Telisotuzumab Adizutecan in Gastric/GEJ Cancer

“[Gastroesophageal cancer] is a disease entity with a significant unmet need where patients still have fairly short survival times. Therefore, it’s important for us to bring in new classes of therapies to try to improve both quality of life and length of life.”

John H. Strickler, MD, professor, medicine, Division of Medical Oncology, co-leader, Precision Cancer Medicine and Investigational Therapeutics Program, associate director, Clinical Research, Gastrointestinal Oncology, leader, Molecular Tumor Board, Duke Cancer Institute, details the rationale of the phase 1 study (NCT05029882) evaluating telisotuzumab adizutecan (ABBV-400) in patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma.

Data from the phase 1 study presented at the 2024 ESMO Congress showed that in evaluable patients with advanced gastric/GEJ adenocarcinoma who received at least 1 prior line of therapy (n = 42), telisotuzumab adizutecan elicited an overall response rate of 28.6% (95% CI, 15.7%-44.6%) and a clinical benefit rate of 71.4% (95% CI, 55.4%-84.3%).

In many gastroesophageal cancers, c-MET overexpression is common, Strickler explains, making it a relevant target in drug development. Therefore, delivering a cytotoxic payload via an antibody-drug conjugate (ADC) as an entry point into the cell may be effective, he says. Telisotuzumab adizutecan is a novel ADC that previously displayed efficacy signals and was tolerable in patients with MET-amplified colorectal cancer.

He notes that unmet needs remain in gastric/GEJ cancer, specifically regarding shorter survival times in this patient population. The ability to provide new classes of therapies to address these unmet needs is crucial in improving quality of life and longer-term survival outcomes, Strickler emphasizes.

The phase 1 study is assessing adverse effects (AEs) and changes in disease activity following the treatment of telisotuzumab adizutecan in patients with advanced solid tumors. However, a dose expansion was evaluated among a cohort of patients specifically with advanced gastric/GEJ cancer (n = 42). Those who experienced progressive disease after no more than 2 prior cytotoxic chemotherapy regimens were treated with telisotuzumab adizutecan at 3.0 mg/kg every 3 weeks.

Most safety concerns following treatment were related to the cytotoxic chemotherapy component of the ADC. AEs commonly experienced with telisotuzumab adizutecan included anemia, neutropenia, thrombocytopenia, nausea, and fatigue.