Phase 1b study evaluating the efficacy and safety of ABBV-400, a c-Met–targeting antibody-drug conjugate, in select advanced solid tumor indications.
Authors: Ruth Perets, Manish Sharma, John H Strickler, Talia Golan, Antoine Hollebecque, William Henner, Athanasios Vasilopoulos, Gladys Morrison Thiele, Michael Charles Burns, James J. Harding
Journal: Journal of Clinical Oncology (2024)

TPS3162 Background: c-Met (MET protein) is commonly overexpressed in a number of tumors, including hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), biliary tract cancers (BTC), esophageal squamous cell carcinoma (ESCC), breast cancer (BC), and head and neck squamous cell carcinoma (HNSCC). Patients with c-Met–overexpressing tumors represent an underserved population, with the need for more effective c-Met–targeting therapies to become available. ABBV-400 is an antibody-drug conjugate, consisting of the c-Met–targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload. Initial results from the ongoing first-in-human study (NCT05029882) of ABBV-400 in patients with advanced solid tumors indicate a tolerable safety profile, with a maximum tolerated dose of 3 mg/kg once every 3 weeks (Q3W), and promising antitumor activity, with an overall response rate of 24.4% (1). Herein, we describe a signal-seeking study evaluating ABBV-400 treatment in patients with select solid tumors. Methods: Multicenter, open-label, phase 1 signal-seeking study(NCT06084481). Eligible patients (≥18 years) have confirmed locally advanced/metastatic disease measurable per RECIST v1.1 and Eastern Cooperative Oncology Group performance status ≤1. Approximately 220 patients are planned for enrollment across 7 cohorts (HCC, n=40; PDAC, n=40; BTC, n=20; ESCC, n=40; triple-negative BC, n=20; hormone receptor-positive/HER2-negative BC, n=20; HNSCC, n=40). The primary objectives are to assess efficacy and safety/tolerability of ABBV-400 in each tumor indication. Secondary objectives include the evaluation of pharmacokinetics (PK) and immunogenicity of ABBV-400. Pharmacodynamic (PD) and biomarker analyses are exploratory endpoints. Patients receive intravenous ABBV-400 at 3 mg/kg Q3W until disease progression, intolerable toxicity, or any other per-protocol discontinuation criteria. c-Met expression will be assessed retrospectively by immunohistochemistry. The maximum treatment duration is 2 years. Tumor assessments are performed at screening and every 6 weeks from the first dose of study drug, with objective response rate as primary efficacy endpoint and duration of response, clinical benefit rate, progression-free survival, and overall survival as secondary efficacy endpoints. Safety evaluations include adverse events monitoring (graded according to the NCI CTCAE, v5.0), physical examinations, vital sign measurements, ECG variables, and clinical laboratory testing. Blood samples for PK, PD, and biomarker analysis are collected at designated time points throughout the study. Enrollment started in November 2023. As of 19 January 2024, 24 patients have been enrolled. 1. Sharma et al. JCO 2023;41[16 suppl]:3015. Clinical trial information: NCT06084481 .