ABBV-400, a c-Met protein–targeting antibody-drug conjugate (ADC), in patients (pts) with advanced gastric/gastroesophageal junction adenocarcinoma (GEA): Results from a phase I study

Backgroundc-Met protein (also known as MET protein) overexpression occurs in several cancers, including GEA. ABBV-400 is an ADC consisting of the c-Met–targeting mAb telisotuzumab conjugated to a novel topoisomerase 1 inhibitor payload. A phase 1 study (NCT05029882) of ABBV-400 in adults with advanced solid tumors is ongoing, and in dose escalation ABBV-400 had a tolerable safety profile and antitumor activity in a number of different tumors. The dose expansion results from the GEA cohort are presented here.MethodsPts with advanced GEA that progressed after ≤2 prior cytotoxic chemotherapeutic regimens received ABBV-400 3.0 mg/kg Q3W. The primary objectives were ABBV-400 safety, tolerability, PK, and efficacy. Tumor c-Met protein expression was evaluated centrally by IHC.ResultsA total of 42 pts were enrolled; median age was 60 years. Median prior lines of therapy was 2 (range 1–5). Median follow-up was 5.6 months and median time on treatment was 3.8 months (range 0.7–8.8);10 pts remain on treatment as of this data cut. TEAEs of any grade (G)/G≥3 occurred in all (100%)/37 (88.1%) pts, the majority being gastrointestinal (32; 76.2%) and hematologic (31; 73.8%). Of these, anemia (28; 66.7%), nausea (20; 47.6%), thrombocytopenia and constipation (11; 26.2% each) and neutropenia (10; 23.8%) were the most common (>20%). The unadjudicated ILD/pneumonitis rate was 9.5%. Median relative dose intensity was 92.9%. 7 (16.7%) pts discontinued due to TEAEs. ORR in all enrolled pts was 28.6%; additional responses are reported in the table. Exploratory biomarker analysis is ongoing to establish the association between c-Met expression and treatment response. Table: 1439P Preliminary efficacya Outcome GEA (n=42) Confirmed best overall response,b n (%) CR 1 (2.4) PR 11 (26.2) SD 18 (42.9) PD 10 (23.8) NE 2 (4.8) ORR,b n (%) 12 (28.6) CBR,b n (%) 30 (71.4) CBR duration: >12 wk 17 (40.5) >24 wk 12 (28.6) Median PFS, mo [95% CI] 4.0 [2.8, 5.0] PFS probability at 3/6 mo 0.59/0.15 CBR, clinical benefit rate; CI, confidence interval; CR, complete response; NE, not evaluable/estimated; NR, not reached; ORR, objective response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease.aOverall survival and duration of response data are immature.bConfirmed responses. ConclusionsABBV-400 demonstrated a tolerable safety profile and antitumor activity in pts with advanced GEA, warranting additional study in future clinical trials.Clinical trial identificationNCT05029882.Editorial acknowledgementMedical writing support was provided by Elaine M. Jennings, PhD, of Aptitude Health, The Hague, the Netherlands.Legal entity responsible for the studyAbbVie.FundingAbbVie.DisclosureJ.H. Strickler: Financial Interests, Personal, Advisory Board: Seagen, AstraZeneca, Amgen, Pfizer, Bayer, AbbVie, Natera, Viatris, BeiGene, Silverback Therapeutics, Daiichi Sankyo, Eli Lilly, Roche Genentech, Takeda, Zentalis, Taiho; Financial Interests, Personal, Other, Consulting: GSK, Pionyr Immunotherapeutics; Financial Interests, Institutional, Coordinating PI: Seagen, Amgen; Financial Interests, Institutional, Local PI: Roche Genentech, AbbVie, AstraZeneca, Astar D3, Bayer, Curegenix, Nektar, Leap Therapeutics, Daiichi Sankyo, Erasca, BeiGene, Silverback Therapeutics. J. Raimbourg: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Pierre Fabre, Amgen, Sanofi; Financial Interests, Institutional, Advisory Board: Takeda, BMS, Merck. F. Ghiringhelli: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Amgen, Merck Serono, MSD. J.E. Cohen: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Medison; Financial Interests, Personal, Other, Travel, accommodation and expenses: Medison. C. Kitagawa: Financial Interests, Personal, Invited Speaker: Oono Yakuhin, Chugai Pharma, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Daiichi Sankyo/AstraZeneca, Sanofi, MSD, AbbVie, ALX oncology, Ono Takuhin. M.R. Sharma: Financial Interests, Personal, Stocks or ownership: Abbott Laboratories, AbbVie, Amgen, Biogen, Bristol Myers Squibb, Gilead Sciences, Johnson & Johnson/Janssen, Lilly, Merck, Moderna Therapeutics, Pfizer, Regeneron, Vertex, West Pharmaceutical; Financial Interests, Personal, Advisory Role: Pliant; Financial Interests, Institutional, Research Funding: AbbVie, Agenus, Alexo Therapeutics, Alkermes, Alpine Immune Sciences, Arrys Therapeutics, Ascentage Pharma, Astellas Pharma, AstraZeneca, Bolt Biotherapeutics, Bristol Myers Squibb, Celgene, Compugen, Constellation Pharmaceuticals, Cullinan Oncology, CytomX Therapeutics, Debiopharm Group, Epizyme, Exelixis, Genmab, Gilead Sciences, GSK/Tesaro, Helsinn Therapeutics, Ikena Oncology, Inhibrx, Johnson & Johnson/Janssen, Jounce Therapeutics, Kinnate Biopharma, KLUS Pharma, KSQ Therapeutics, Loxo, MacroGenics, Merck, Mersana, NGM Biopharmaceuticals, Odonate Therapeutics, Onconova Therapeutics, Palleon Pharmaceuticals, Pfizer, PureTech, Regeneron, Repare Therapeutics, Samumed, Sapience Therapeutics, Seagen, Seven and Eight Biopharmaceuticals, Shattuck Labs, SK Life Science, Symphogen, Syros Pharmaceuticals, Tempest Therapeutics, Theratechnologies, Tizona Therapeutics, Inc., Treadwell Therapeutics; Financial Interests, Institutional, Research Grant: eFFECTOR Therapeutics. K.H. Lee: Financial Interests, Personal, Advisory Board: BMS, MSD, Eli Lilly, Yuhan, Pfizer, AstraZeneca; Financial Interests, Funding: Merck. M. De Miguel: Financial Interests, Institutional, Invited Speaker: Janssen, MSD; Non-Financial Interests, Principal Investigator: Janssen, MSD, Roche, PharmaMar, Replimune, Novartis, AbbVie, Achilles, Amunix, Arcus, Furmo, BioNTech, Catalym, Dizal, Genentech, Loxo, Numab, Seagen. Z.N. Hunter, M. Burns, R.R. Li, N. Rudraganguly, C. Biesdorf de Almeida, K.J. Freise, M.E. Blaney, G. Morrison-Thiele, M.R. Neagu Aristide: Financial Interests, Personal, Full or part-time Employment, AbbVie employees and may own stock: AbbVie. Y. Kuboki: Financial Interests, Personal, Advisory Board: Takeda, Amgen, Abbie, Incyte, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Taiho, Lilly; Financial Interests, Institutional, Local PI: Taiho, Astellas, Lilly, Takeda, AstraZeneca, Boehringer Ingelheim, Chugai, Genmab, Incyte, Abbie, Merck, Novartis, Hengrui; Financial Interests, Institutional, Coordinating PI: Amgen; Non-Financial Interests, Member: JSMO, ASCO, JSCO, JCA.