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

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

NCT05029882.

Editorial acknowledgement

Medical writing support was provided by Sravya Kotaru, PhD from Aptitude Health, Atlanta, GA, and funded by AbbVie.

Legal entity responsible for the study

AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract.

Funding

This study was funded by AbbVie. No honoraria or payments were made for authorship.

Disclosure

J.H. Strickler: Financial Interests, Personal, Other, Consulting: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Daiichi Sankyo, Eli Lilly, GSK, Natera, Pfizer, Pionyr Immunotherapeutics, Roche/Genentech, Seagen, Silverback Therapeutics, Takeda, Viatris, Zentalis; Financial Interests, Personal, Research Funding: AbbVie, Amgen, Astar D3, Bayer, BeiGene, Curegenix, Daiichi Sankyo, Eli Lilly, Erasca, Gossamer Bio, Leap Therapeutics, Nektar, Roche/Genentech, Seagen, Silverback Therapeutics. D.R. Camidge: Financial Interests, Personal, Other, Honoraria: AbbVie, Amgen Astellas BioPharma, AnHeart Therapeutics, Apollomics, AstraZeneca, BeiGene, Bio-Thera, Blueprint Medicines, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Elevation Oncology, EMD Serono, GSK, Helsinn Therapeutics, Hengrui Pharmaceutical, Janssen, Kestrel Labs, Lilly, Mersana, Nuvalent Inc., OnKure, Pfizer, Puma Biotechnology, Qilu Pharmaceutical, Ribon Therapeutics, Roche, Sanofi, Seattle Genetics, Takeda, Turning Point Therapeutics; Financial Interests, Personal, Research Funding, Honoraria: Inivata (Inst). Y. Kuboki: Financial Interests, Personal, Research Funding: Taiho, Astellas, Lilly, Takeda, Daiichi Sankyo, AstraZeneca, Boehringer Ingelheim, Chugai, Genmab, GSK, Incyte, AbbVie, Amgen; Financial Interests, Personal, Advisory Role: Takeda, Amgen, Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Taiho, Lilly, Bristol Myers Squibb. N. Yamamoto: Financial Interests, Personal, Research Grant: Rakuten Medical, Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Kyowa Kirin, Takeda, Ono, Janssen Pharma, Merck Sharp & Dohme, Merck, GSK, Sumitomo Pharma, Chiome Bioscience, Otsuka, Carna Biosciences, Genmab, Shionogi, Toray, Kaken, AstraZeneca, Cimic; Financial Interests, Personal, Other, Personal fees: Ono Pharmaceutical, Chugai, Daiichi Sankyo, Eisai, Takeda, Otsuka, Boehringer Ingelheim, Cimic, Healios. D. Sommerhalder: Financial Interests, Personal, Other, Employee: Texas Oncology, US Oncology; Financial Interests, Personal, Other, Honoraria: Syneos; Financial Interests, Personal, Research Funding: AbbVie, ADC Therapeutics, Ascentage Pharma Group, Astellas, Biomea Fusion, Boehringer Ingelheim, BJ Bioscience, BioNTech, Fate Therapeutics, Gilead Sciences, Immuneering, Kura Oncology, Monopteros Therapeutics, Navire Pharma Inc., Nimbus Saturn Inc., NGM Biopharmaceuticals, Parthenon, Pfizer, Revolution Medicines, Mirati Therapeutics, Symphogen, Teon Therapeutics, Medilink Therapeutics, ZielBio Inc. A. Vasilopoulos, R.R. Li, K. Freise, G. Morrison-Thiele, M.R. Neagu Aristide: Financial Interests, Personal, Stocks/Shares, Employee and may own stock: AbbVie Inc. J. Bar: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, Bayer, BMS, Causalis, Eisai, MSD, Novartis, Roche, Takeda; Financial Interests, Personal, Research Funding: ImmuneAI, OncoHost, MSD, AstraZeneca.