Abstract 691P
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.
Resources from the same session
689P - DB-1305 (a Trop-2 targeted antibody-drug-conjugate [ADC]) in patients (pts) with advanced solid tumors: Preliminary clinical results from the phase (Ph) I/IIa study
Presenter: Omkar Marathe
Session: Poster session 17
690P - Ifinatamab deruxtecan (I-DXd; DS-7300) in patients with advanced solid tumors: Updated clinical and biomarker results from a phase I/II study
Presenter: Manish R Patel
Session: Poster session 17
692P - First-in-human study of ELU001, a targeted nanoparticle drug conjugate, in subjects with folate receptor α (FRα) overexpressing solid tumors
Presenter: Wen wee Ma
Session: Poster session 17
693P - Preclinical activity of HLX43, a PD-L1-targeting ADC, in multiple PD-1/PD-L1 refractory/resistant models
Presenter: Yongqiang Shan
Session: Poster session 17
694P - Full efficacy analysis of phase I/II trial investigating bexmarilimab, a novel macrophage-guided immunotherapy in refractory solid tumors
Presenter: Petri Bono
Session: Poster session 17
695P - A phase I/Ib study evaluating the safety and tolerability of NIZ985 alone and in combination with spartalizumab (anti–PD-1) in patients (pts) with solid tumors or lymphoma
Presenter: Elena Garralda
Session: Poster session 17
696P - SIM1811-03 (SIM0235), an anti-tumor necrosis factor receptor-2 (TNFR2) monoclonal antibody, in patients with advanced solid tumor and/or cutaneous T cell lymphomas (CTCL): Preliminary results from an on-going first-in-human phase I trial in China
Presenter: Furong Liu
Session: Poster session 17
699P - Immunogenicity and reactogenicity of BNT162b2 COVID-19 mRNA vaccine in long-survivor (LS) patients with metastatic lung cancer (mLC) after primary immunization (PV) and booster (BD): COVALENCE study
Presenter: Emanuele Vita
Session: Poster session 17