Abstract 197TiP
Background
Mucin-16 is a cell surface glycoprotein that is overexpressed in epithelial OC. Ubamatamab (REGN4018) is a mucin-16 x cluster of differentiation 3 (MUC16xCD3) bispecific antibody that promotes T cell–mediated cytotoxicity by facilitating contact between cancer cells and T cells. Cemiplimab is an anti–programmed cell death-1 monoclonal antibody. The phase 1 study in patients with recurrent OC found ubamatamab monotherapy had an acceptable safety profile, durable clinical activity across a range of doses (as measured by RECIST and cancer antigen 125 [CA-125] response rates), and linear pharmacokinetics up to 800 mg weekly intravenous (IV)1. These clinical data support further evaluation of a once every 3-week (Q3W) regimen of ubamatamab alone and in combination with cemiplimab.
Trial Design
In phase 2, up to 150 patients with advanced platinum-resistant OC and elevated serum CA-125 will be randomised to three IV arms (1:1:1) to receive ubamatamab 250 mg IV Q3W or 800 mg IV Q3W as monotherapy, or ubamatamab 250 mg IV Q3W in combination with cemiplimab 350 mg Q3W. All arms will include weekly step-up dosing of ubamatamab (1 mg week 1, 20 mg week 2, and full dose weeks 3 and 4) to limit risk of cytokine release syndrome prior to proceeding to Q3W dosing. Expansion cohorts will use a Simon 2-stage study design, with an interim analysis after the first 20 patients. Any arm with ≥3 objective responses will be expanded to 50 patients. In this dose expansion phase the primary endpoint will be the objective response rate for each arm as defined by RECIST 1.1 criteria. Secondary endpoints include evaluation of duration of response and progression-free survival as well as further evaluation of safety and pharmacokinetics. Exploratory endpoints include evaluation of baseline tumour MUC16 immunohistochemistry expression and other biomarkers as predictors of response. The impact of ubamatamab on quality of life and physical functioning will also be assessed. Final data are pending for this TiP. Reference 1: Annals of Oncology (2022) 33 (suppl_7): S235-S282. 10.1016/iotech/iotech1054.
Clinical trial identification
NCT03564340.
Editorial acknowledgement
Medical writing support was provided by Rachel McGrandle, BSc, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc.
Legal entity responsible for the study
Regeneron Pharmaceuticals, Inc.
Funding
Regeneron Pharmaceuticals, Inc.
Disclosure
K.N. Moore: Financial Interests, Personal, Advisory Role: AstraZeneca, Aravive, Alkemeres, Blueprint Pharma, Caris, Elevar, Eisai, Genentech/Roche, GSK/Tesaro, Hengrui, Immunogen, Inxmed, IMab, Iovance, Lilly, Mereo, Myriad, Mersana, Novocure, Novartis, Tarveda, Verastem and VBL Therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca, Regeneron, Novocure, Genentech/Roche, AbbVie, GSK/Tesaro, Immunogen, PTC Therapeutics, Merck, Lilly, Mereo, Artios and Daichii. S. Bouberhan: Financial Interests, Personal, Advisory Role: ImmunoGen. E. Hamilton: Financial Interests, Institutional, Research Grant: Regeneron, AbbVie, Acerta Pharma, ADC Therapeutics, Akesobio Australia, Amgen, Aravive, ArQule, Arvinas, AstraZeneca, AtlasMedX, Black Diamond, Boehringer Ingelheim, Clovis, Compugen, Curis, CytomX, Dana Farber Cancer Inst, Daiichi Sankyo, Deciphera, eFFE; Financial Interests, Institutional, Advisory Role: Arcus, Arvinas, AstraZeneca, Black Diamond, Boehringer Ingelheim, CytomX, Daiichi Sankyo, Dantari, Deciphera Pharmaceuticals, Eisai, H3 Biomedicine, iTeos, Janssen, Lilly, Loxo, Merck, Mersana, Novartis, Pfizer, Puma Biotechnology, Relay Therapeutics, Roc. J. Liu: Financial Interests, Personal, Advisory Role: AstraZeneca, Clovis Oncology, Eisai, EpsilaBio, Genentech/Roche, GlaxoSmithKline and Regeneron Pharmaceuticals, Inc.; Financial Interests, Institutional, Research Grant: 2X Oncology, Aravive, Arch Oncology, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, CytomX Therapeutics, GlaxoSmithKline, Regeneron, Surface Oncology, Tesaro, Vigeo Therapeutics and Zentalis. R.E. O'Cearbhaill: Financial Interests, Personal, Other, Personal fees: Tesaro/GSK, Regeneron, Seattle Genetics, Fresenius Kabi, Bayer, Immunogen, Curio and MJH; Financial Interests, Personal, Other, Travel support for meeting: Hitech Health; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Role: PRIMA, Moonstone (Tesaro/GSK) and DUO-O (AstraZeneca); Non-Financial Interests, Personal, Advisory Role: Carina Biotech; Financial Interests, Institutional, Research Grant: Bayer/Celgene/Juno, Tesaro/GSK, Merck, Ludwig Cancer Institute, AbbVie/StemCentrx, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, MarkerTherapeutics, Syndax Pharmaceuticals, Genmab/Seagen Therapeutics, Sellas Therapeutics, Genentech, Kite Pharma and. D. O'Malley: Financial Interests, Personal, Advisory Role: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/Johnson & Johnson, AbbVie, Regeneron, Amgen, Novocure, Genentech/Roche, GOG Foundation, Iovance, Eisai, Agenus, SeaGen, Mersana, Clovis and SDP Oncology (BBI), Ambry, Myriad Genetics, Tarveda, Novartis, Rubis, Elevar, Takeda, Toray, INXMED, Arquer Diagnostics, Roche Diagnostics MSA, Sorrento, Corcept Therapeutics and Celsion Corp; Financial Interests, Personal, Research Grant: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/Johnson & Johnson, AbbVie, Regeneron, Amgen, Novocure, Genentech/Roche, GOG Foundation, Iovance, Eisai, Agenus, SeaGen, Mersana, Clovis and SDP Oncology (BBI), VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research, Stemcentrx, Inc., Cerulean Pharma, Bristol Myers Squibb Co., Serono Inc., TRACON Pharmaceuticals, New Mexico Cancer Care Alliance, INC Research, Inc., inVentiv Health C. S. Yoo: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. M. Peterman: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. P. Goncalves: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. T. Schmidt: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. M. Zhu: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. I. Lowy: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. T. Uldrick: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. E.A. Miller: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.