Telisotuzumab Adizutecan (ABBV-400), a Novel c-Met–Targeting Antibody–Drug Conjugate: First-in-Human Results in Advanced Gastric/Gastroesophageal Junction Cancer

PURPOSE: Gastrointestinal tumors, including esophageal and gastric/gastroesophageal junction adenocarcinoma (GEA), have a high mortality rate and present significant treatment challenges. Telisotuzumab adizutecan (Temab-A, ABBV-400), a novel antibody-drug conjugate targeting the c-Met protein (also known as MET protein), has shown encouraging results in patients with advanced GEA. PATIENTS AND METHODS: This phase I, open-label, multicenter study assessed the safety, efficacy, and pharmacokinetics (PK) of Temab-A monotherapy (3 mg/kg every 3 weeks intravenously) in patients with advanced GEA. Patients ≥18 years of age with advanced/metastatic GEA who had received 1 to 2 prior systemic therapies were included. The primary objectives were the evaluation of safety, PK, and efficacy; efficacy endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). c-Met expression and MET amplification were retrospectively assessed. RESULTS: Forty-two patients with advanced GEA were enrolled; the median age was 60 years. The median follow-up duration was 12.6 months. All patients had one or more treatment-emergent adverse events (TEAE), with 88% experiencing grade ≥3 TEAEs. The most common hematologic TEAEs were anemia (67%), nausea (52%), and decreased appetite (36%). The ORR was 29%, the clinical benefit rate was 71%, and the median DOR was 4.2 months. The median PFS was 4 months, and the median OS was 5.8 months. Exploratory biomarker analyses showed ORR enrichment in patients with higher c-Met protein expression and MET focal amplification. CONCLUSIONS: Temab-A monotherapy demonstrated antitumor activity and a manageable safety profile in patients with advanced GEA. The findings support further clinical development of Temab-A, particularly in combination with other agents to improve outcomes for patients with 2L+ GEA.