691P Efficacy of ABBV-400 monotherapy in patients with MET gene amplified advanced solid tumors

Anti–c-Met (MET protein) antibody-drug conjugate ABBV-400 comprises monoclonal antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor via a stable, cleavable linker. MET gene amplification (amp) occurs at low frequency in primary tumors (<5%) but has increased frequency in recurrent/refractory disease. ABBV-400 showed deep, durable responses in preclinical patient (pt)-derived xenograft models of MET amp, c-MET–overexpressing advanced solid tumors. A first-in-human phase I study (NCT05029882) is evaluating safety, pharmacokinetics, and preliminary efficacy of ABBV-400 in pts with advanced solid tumors; we present results of an ad hoc analysis of efficacy in pts with MET amp. Analyzed pts had measurable disease per RECIST v1.1 and history of advanced solid tumors that progressed/were not amenable to any available therapies/surgery. Pts had MET amp per local NGS reports of tissue/blood samples from various approved labs. ABBV-400 administered intravenously once every 3 weeks. As of 3 Apr 2023, 11 pts with MET amp advanced solid tumors were treated with ABBV-400 at 2.4 (N=4), 3 (N=6), or 4 (N=1) mg/kg; median follow-up 6.7 months. Enrolled tumor types included NSCLC, intrahepatic cholangiocarcinoma, gastroesophageal, ovarian, urachal, colorectal, and breast cancers. Median age 65 (range 41–73) years, 64% male, 64% Asian, 27% White, 9% Black, 6 (55%)/5(45%) had ECOG PS 0/1; median prior lines of therapy 3 (range 1–6). Pts had MET IHC H-score range of 73–270 and 5–75% cells with 3+ staining (data available for 6/11 pts). Treatment-emergent AEs reported in 11 pts (100%; 55% grade ≥3); most commonly, neutropenia (55%), anemia (46%), nausea (46%), and leukopenia (46%). Confirmed partial response observed in 8 pts (ORR = 73%, 95% CI: 39, 94) per investigator review and RECIST v1.1; 6 pts had ongoing response. Median progression-free survival was 10.8 months (95% CI: 1.2, not reached [NR]), duration of response and overall survival NR; longest ongoing response was >9 months. ABBV-400 monotherapy showed promising tolerability and efficacy in pts with various MET amp advanced solid tumors. Based on these results, MET amp cohort will be expanded to 60 more pts.