754P - Ubamatamab (MUC16xCD3 bispecific antibody) with cemiplimab (anti-PD-1 antibody) in recurrent ovarian cancer: Phase I dose-escalation study

Background

Ubamatamab (REGN4018) is a mucin16 (MUC16) x CD3 bispecific antibody. Cemiplimab, an anti-PD-1 antibody, enhanced its activity in preclinical studies. In phase 1 (NCT03564340), ubamatamab monotherapy resulted in an acceptable safety profile and durable responses. We now present ubamatamab combined with cemiplimab dose escalation results.

Methods

Patients (pts) with recurrent platinum-experienced ovarian cancer (OC) received weekly intravenous (IV) ubamatamab at a dose range of 1–450 mg after initial step-up dosing. Cemiplimab 350 mg IV every 3 weeks was added beginning Day 29–36. Dose escalation initially followed a modified 3+3 design, then Bayesian optimal interval design. Primary endpoints were safety and PK. Secondary endpoints included confirmed objective response rate (ORR), Kaplan-Meier estimated duration of response (DoR) and progression-free survival (PFS) (RECIST 1.1), and CA125 response (GCIG).

Results

35 pts were enrolled, 29 (82.9%) received ≥1 dose of cemiplimab. Median number of prior therapies was 5 (range 1−10). Median duration of ubamatamab and cemiplimab exposure was 11 (range 2−75) and 12 (3−69) weeks, respectively. The most common treatment-emergent adverse events (TEAE) were pain (82.9%) and cytokine release syndrome (68.6%, all Grade [G] 1/2). The most common G≥3 TEAE were anaemia (25.7%), pain (20.0%) and neutropaenia (11.4%, 1 dose-limiting toxicity [DLT], 60 mg). Ubamatamab 1–250 mg weekly with cemiplimab was tolerable. In the highest dose cohort (450 mg), haemophagocytic lymphohistiocytosis (G4, DLT) was observed. Objective responses were observed at ubamatamab doses 10–250 mg (n=25). In 22 of these pts receiving ≥1 dose of cemiplimab, ORR was 18.2% (95% CI: 5.2–40.3), median DoR 8.3 months (4.2–not estimable), CA125 response rate 22.7% (7.8–45.4) and 6-month PFS 47.6% (25.7–66.7). Two pts with target lesion growth (+17%, +31%) before adding cemiplimab to ubamatamab had subsequent partial responses. Ubamatamab PK was not impacted by cemiplimab.

Conclusions

In pts with heavily pretreated OC, an acceptable safety profile and durable responses were observed with ubamatamab + cemiplimab. A randomised phase 2 expansion of ubamatamab +/- cemiplimab is ongoing.

Clinical trial identification

NCT03564340.

Editorial acknowledgement

Writing assistance was provided by Brian Head, PhD, of Regeneron Pharmaceuticals, Inc.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc.

Funding

Regeneron Pharmaceuticals, Inc.

Disclosure

R.E. O'Cearbhaill: Financial Interests, Personal, Other, Personal Fees: Bayer, Curio, Fresenius Kabi, Immunogen, MJH, Regeneron, Seattle Genetics, and Tesaro/GSK; Financial Interests, Personal, Other, Travel: Hitech Health ; Financial Interests, Personal, Advisory Board: GSK; Non-Financial Interests, Personal, Steering Committee Member: PRIMA, Moonstone (Tesaro/GSK) and DUO-O (AstraZeneca) studies; Non-Financial Interests, Personal, Advisory Role: Carina Biotech; Financial Interests, Institutional, Research Funding: AbbVie/StemCentrx, Atara Biotherapeutics, Bayer/Celgene/Juno, Genentech, Genmab/Seagen Therapeutics, Gynecologic Oncology Foundation , Kite Pharma, Ludwig Cancer Institute, Marker Therapeutics, Merck, Regeneron, Sellas Therapeutics, Syndax Pharmaceuticals, ; Financial Interests, Personal, Other, NRG representative: ComboMATCH study. K.N. Moore: Financial Interests, Personal, Advisory Board, Personal fees (consulting and/or advisory boards): Alkemeres, Aravive, AstraZeneca, Blueprint Pharma, Caris, Eisai, Elevar, Genentech/Roche, GSK/Tesaro, Hengrui, IMab, Immunogen, Inxmed, Iovance, Lilly, Mereo, Mersana, Myriad, Novartis, Novocure, Tarveda, VBL Therapeutics and Verastem; Financial Interests, Institutional, Research Funding: AbbVie, Artios, AstraZeneca, Daiichi Sankyo, Genentech/Roche, GSK/Tesaro, Immunogen, Lilly, Merck, Mereo, Novocure, PTC Therapeutics and Regeneron. O. Yeku: Financial Interests, Personal, Advisory Board: Celldex, GIMV NV, hC Bioscience and TigaTx. J.F. Liu: Financial Interests, Personal, Advisory Board, Personal fees (consulting and/or advisory boards): AstraZeneca, Clovis Oncology, Eisai, EpsilaBio, Genentech/Roche, GSK and Regeneron Pharmaceuticals, Inc.; Financial Interests, Institutional, Research Funding: 2X Oncology, Aravive, Arch Oncology, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, CytomX Therapeutics, GSK, Regeneron, Surface Oncology, Tesaro, Vigeo Therapeutics and Zentalis. S. Bouberhan: Financial Interests, Personal, Speaker, Consultant, Advisor: ImmunoGen. 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, eFFE; Financial Interests, Institutional, Speaker, Consultant, Advisor: 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. S. Yoo, S. Govindraj, J. Brouwer-Visser, M. Peterman, T. Schmidt, B. Barnes, P. Madia, M. Zhu, T.S. Uldrick, E.A. Miller: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. D. O'Malley: Financial Interests, Personal, Research Funding: AbbVie, Agenus, Amgen, AstraZeneca, Celsion Corp, Clovis, Corcept Therapeutics, Eisai, GOG Foundation , Immunogen, Iovance, Janssen/Johnson & Johnson, Mersana, Novocure and Genentech/Roche, Regeneron, SDP Oncology (BBI), Seagen and Tesaro/GSK, Ajinomoto Inc., Array Biopharma, Bristol Myers Squibb Co., Cerulean Pharma, EMD Serono, Ergomed, Inc. Research, Inc., inVentiv Health Clinical PRA Intl, Ludwig Cancer Research, Merck and GenMab, New Mexico Cancer Care Alliance, Serono Inc., Stemcentrx, Inc; Financial Interests, Personal, Advisory Board, Personal fees (consulting and/or advisory boards): Ambry, Arquer Diagnostics, Elevar, INXMED, Myriad Genetics, Novartis, Rubis, Roche Diagnostics MSA, Sorrento, Takeda, Tarveda and Toray, AbbVie, Agenus, Amgen, AstraZeneca, Celsion Corp, Clovis, Corcept Therapeutics, Eisai, GOG Foundation, Immunogen, Iovance, Janssen/Johnson & Johnson, Mersana, Novocure and Genentech/Roche, Regeneron, SDP Oncology (BBI), Seagen and Tesaro/GSK. All other authors have declared no conflicts of interest.