Abstract 41P
Background
Ubamatamab (REGN4018) is a mucin 16 x cluster of differentiation 3 (MUC16xCD3) bispecific antibody that promotes T cell–mediated cytotoxicity by binding MUC16-expressing ovarian cancer (OC) cells and CD3+ T cells. We present safety, efficacy and pharmacokinetic (PK) modelling from a first-in-human study of ubamatamab (NCT03564340).
Methods
Patients (pts) with recurrent platinum-experienced OC received ubamatamab 0.3–800 mg intravenously weekly (QW) after initial step-up dosing. Primary endpoints were safety and PK. Secondary and exploratory endpoints included objective response rate per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, disease control rate (a response or stable disease) and cancer antigen 125 (CA-125) response per Gynecological Cancer InterGroup criteria.
Results
78 pts received ubamatamab 0.3–800 mg without reaching maximal tolerated dose. Median number of prior therapies was 4.5 (range 1–17). Median ubamatamab exposure was 12 (range 1–117) weeks. Commonest treatment-emergent adverse events (TEAEs) were cytokine release syndrome (73.1%, all Grade 1/2) and pain (87.2%), primarily occurring in Weeks 1–2 of step-up dosing. Commonest Grade ≥3 TEAEs were anemia (24.4%) and abdominal pain (20.5%). Objective responses were observed between 20–800 mg. In 42 pts receiving ≥1 full dose of ≥20 mg, ORR was 14.3% (95% CI, 5.4–28.5), disease control rate was 57.1% (41–72.3), and median duration of response was 12.2 months. 23.8% of pts (12.1–39.5%) had a CA-125 response. Serum ubamatamab concentrations increased dose proportionally. No apparent dose-response relationship was observed from 20–800 mg for safety or efficacy. PK modelling supported the selection of 250 and 800 mg every-3-weeks (Q3W) regimens for Phase 2, as both regimens had a maximum concentration (Cmax) below the Cmax of 800 mg QW, and trough concentration (Cmin) above that of the minimal effective dose (20 mg QW).
Conclusions
Ubamatamab resulted in an acceptable safety profile and durable responses in a heavily pretreated OC population across a wide dose range. A randomised Phase 2 expansion trial with initial step-up dosing followed by Q3W dosing has been initiated.
Clinical trial identification
NCT03564340.
Editorial acknowledgement
Editorial support was provided by Rachel McGrandle of Prime Medica, 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 Daiichi. D. O'Malley: 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; 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. 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, eFFECTOR Therap; 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. R.E. O'Cearbhaill: Financial Interests, Personal, Invited Speaker, Personal fees: Tesaro/GSK, Regeneron, Seattle Genetics, Fresenius Kabi, Bayer, Immunogen, R-Pharm, Onclive, Curio and MJH; Financial Interests, Personal, Other, Travel support for meeting: Hitech Health; Non-Financial Interests, Personal, Advisory Role, Steering committee: PRIMA, Moonstone (Tesaro/GSK) and DUO-O (AstraZeneca) studies; 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; Financial Interests, Personal, Other, NRG representative: ComboMATCH study. O. Yeku: Financial Interests, Personal, Advisory Role: Celldex, GIMV NV, TigaTx and hC Bioscience. S. Bouberhan: Financial Interests, Personal, Advisory Role: ImmunoGen. 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, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. S. Yoo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M. Zhu: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: 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. Rowlands: 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, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. 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. All other authors have declared no conflicts of interest.