523MO - Ubamatamab (REGN4018, MUC16xCD3 bispecific antibody) monotherapy in patients with recurrent ovarian cancer (OC): Phase I dose-escalation analysis

Background

Ubamatamab is a mucin-16 x cluster of differentiation 3 (MUC16xCD3) bispecific antibody that promotes T cell–mediated cytotoxicity by binding MUC16-expressing OC cells and CD3+ T cells. We present safety, pharmacokinetics (PK) and efficacy from a first-in-human Phase 1 study of ubamatamab (NCT03564340).

Methods

Patients with advanced platinum-experienced OC and elevated serum cancer antigen 125 were administered ubamatamab monotherapy intravenously weekly at a dose range of 0.1–800 mg after initial step-up dosing. Dose escalation followed a modified 3+3 design. Primary endpoints were safety and PK. Secondary endpoints included preliminary estimate of objective response rate (ORR) per RECIST 1.1.

Results

78 patients received ubamatamab; median number of prior therapies was 4.5 (range 1–17). Median duration of exposure was 12 (range 0.4–117) weeks. The most common treatment-emergent adverse events (TEAE) were cytokine release syndrome (73.1%, all Grade 1/2) and pain (87.2%) that primarily occurred during Weeks 1–2 of initial step-up dosing. The most common Grade ≥3 TEAEs were anaemia (23.1%) and abdominal pain (19.2%). Objective responses were observed between 20–800 mg doses (n=50). ORR of those receiving ≥1 full dose (n=42) was 14.3% (95% CI 5.4–28.5) and disease control rate (DCR) was 57.1% (41.0–72.3). Median duration of response was 12.2 months. In a subset of these patients without baseline visceral metastases (n=29) ORR was 20.7% (8.0–39.7) and DCR was 72.4% (52.8–87.3). Exploratory analysis of patients with >75% of tumour cells with 2+ baseline MUC16 immunohistochemical staining and ≥1 dose of ≥20 mg (n=13) showed ORR of 30.8% (9.1–61.4), and DCR 61.5% (31.6–86.1). Serum ubamatamab concentrations increased dose-proportionally. No definitive dose-response relationship was observed in safety or efficacy between 20–800 mg.

Conclusions

Ubamatamab safety profile was acceptable with evidence of durable responses in this heavily pretreated population with OC across a wide dose range. Based on data from this study, a randomised Phase 2 expansion has been initiated.

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

D. O'Malley: Financial Interests, Personal, Advisory Role: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/Johnson & Johnson, AbbVie, Regeneron, Amgen, Novocure, Genentech/Roche, GOGFoundation, Iovance, Eisai, Agenus, SeaGen, Mersana, Clovis , SDP Oncology (BBI), Ambry, Myriad Genetics, Tarveda, Novartis, Rubis, Elevar, Takeda, Toray, InxMed, Arquer Diagnostics, Roche Diagnostics MSA, Sorrento, Corcept Therapeutics , Celsion Corp; Financial Interests, Personal, Research Grant: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/Johnson & Johnson, AbbVie, Regeneron, Amgen, Novocure , Genentech/Roche, GOGFoundation, Iovance, Eisai, Agenus, SeaGen, Mersana, Clovis , 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 Clinical PRA Intl, Merck , GenMab. R.E. O'Cearbhaill: Financial Interests, Personal, Advisory Role: Genmab Therapeutics , Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Research Grant: AbbVie, Atara Biotherapeutics, Celgene, Genentech, Genmab Therapeutics, GlaxoSmithKline, Juno, Kite Pharma, Ludwig Cancer Institute, Marker Therapeutics, Regeneron Pharmaceuticals, Inc., Sellas Therapeutics, Syndax Pharmaceuticals, TCR2 Therapeutics, Tesaro. 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, VBL Therapeutic; Financial Interests, Institutional, Research Grant: AstraZeneca, Regeneron, Novocure, Genentech/Roche, AbbVie, GSK/Tesaro, Immunogen, PTC Therapeutics, Merck, Lilly, Mereo, Artios, Daichii. E.P. 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 Therapeutics, Ellipses Pharma, EMD Serono, Fochon, FujiFilm, G1 Therapeutics, H3 Biomedicine, Harpoon, Hutchinson MediPharma, Immunogen, Immunomedics, Incyte, InvestisBio, Jacobio, Karyopharm, Leap Therapeutics, Lilly, Lycera, Mabspace Biosciences, Macrogenics, MedImmune, Merck, Mersana, Merus, Millenium, Molecular Templates, Myriad Genetic Labs, Novartis, Nucana, Olema, OncoMed, Onconova Therapeutics, ORIC Pharmaceuticals, Orinove, Pfizer, PharmaMar, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Plexxikon, Radius Health, Repertoire Immune Medicine, Rgenix, Roche/Genentech, SeaGen, Sermonix Pharmaceuticals, Shattuck Labs, Silverback, StemCentRx, Sutro, Syndax, Syros, Taiho, TapImmune, Tesaro, Treadwell Therapeutics, Verastem, Vincerx Pharma, Zenith Epigenetics , Zymeworks ; Financial Interests, Institutional, Other, Consulting: 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, Roche/Genentech, SeaGen , Silverback Therapeutics . O. Yeku: Financial Interests, Personal, Advisory Role: Celldex, GIMV NV, TigaTx , hC Bioscience. S. Bouberhan: Financial Interests, Personal, Advisory Role, consulting fees: ImmunoGen. S. Yoo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. J. Brouwer-Visser: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. H.K. Cheung: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: 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, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: 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, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: 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.S. 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.F. Liu: Financial Interests, Personal, Advisory Role, personal consulting fees: AstraZeneca, Clovis Oncology, Eisai, EpsilaBio, Genentech/Roche, GlaxoSmithKline, 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, Zentalis. All other authors have declared no conflicts of interest.