127P - REGN5668 (MUC16xCD28 bispecific antibody) with cemiplimab (anti-PD-1 antibody) in recurrent ovarian cancer: Phase 1 dose-escalation study

Background

REGN5668 (R5668) is a mucin16 (MUC16) x CD28 bispecific antibody (bsAb). R5668 provides “signal 2” T-cell costimulation through CD28 in the presence of MUC16 tumor antigen. CD28 bispecifics augment anti-tumor activity of the anti-PD-1 monoclonal Ab cemiplimab (cemi) in preclinical studies. We present the phase 1 dose-escalation results of intravenous (IV) R5668 combined with cemi in patients (pts) with recurrent platinum-experienced ovarian cancer (OC).

Methods

Pts received weekly R5668 IV at a dose range of 0.3-300 mg. Cemi 350 mg IV every 3 weeks was added beginning Day 21-28. Primary endpoints were safety and R5668 PK. Secondary endpoints included confirmed objective response rate (RECIST 1.1) and CA-125 response (Gynecologic Cancer InterGroup). Multiplex cytokine profiling was exploratory.

Results

28 pts were enrolled; 22 (79%) received ≥1 dose of cemi. Median number of prior therapies was 3.5 (range 1−10). Median duration of R5668 and cemi exposure was 7.5 (range 1.9-39.0) and 6.1 (2.4−36.0) weeks, respectively. Fatigue (32%), nausea (29%), and pain (18%) were the most common treatment-related adverse events (TRAEs). Infusion-related reactions/cytokine release syndrome (all Grade [G]1/2) occurred in 14% of pts. One pt had a G≥3 TRAE (fatigue). There were no adverse events resulting in death or study drug discontinuation. No DLTs were observed and opening of the next cohort (1000 mg) is planned. Across all pts treated to date, 1 confirmed partial response (-59% target lesion reduction from baseline) and 1 CA-125 response were observed, both in a single pt at 300 mg. 6 (21%) pts had stable disease. There was a dose-dependent increase in R5668 exposure between 1 mg and 300 mg IV QW dosing. Cytokine analyses revealed no apparent elevations after R5668 dosing, while upon cemi addition, slight increases in IFNγ and IP10 were observed.

Conclusions

In 28 heavily pretreated OC pts, an acceptable safety profile, low rates of CRS, and early activity were observed with R5668 + cemi. R5668 dose escalation with cemi or ubamatamab (MUC16xCD3 bsAb) is ongoing.

Clinical trial identification

NCT04590326.

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

I.S. Winer: Financial Interests, Personal, Research Funding: Oncoceutics. R.E. O'Cearbhaill: Financial Interests, Personal, Other, Personal Fees: Bayer, Curio, Fresenius Kabi, Immunogen, MJH, Seattle Genetics and Tesaro/GSK, Miltenyi, 2seventybio; Financial Interests, Institutional, Other, Personal Fees: Regeneron; Financial Interests, Personal, Advisory Board: AbbVie/StemCentrx, Atara , Biotherapeutics, Bayer/Celgene/Juno, Genentech, Genmab/Seagen Therapeutics, Gynecologic OncologyFoundation, Kite Pharma, Ludwig Cancer Institute, Merck, Regeneron, Sellas Therapeutics, Syndax Pharmaceuticals, TCR2 Therapeutics, Lyell Therapeutics, Arsenal-Bio, Tesaro/GSK, GSK; Financial Interests, Personal, Steering Committee Member, Non-Compensated: PRIMA, Moonstone (Tesaro/GSK), and DUO-O (AstraZeneca) studies; Financial Interests, Personal, Advisory Board, Non-Compensated: Carina Biotech; Financial Interests, Personal, Other, Travel for meeting: Hitech Health. S. Bouberhan: Financial Interests, Personal, Other, Consulting Fees: ImmunoGen. J.L. Hays: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck, Tesaro, Clovis Oncology, Deciphera, and Ipsen; Financial Interests, Personal, Other, Travel, accommodations, and expenses: Tesaro, Merck, and AstraZeneca. D.R. Roque: Financial Interests, Personal, Other, Honoraria: Intuitive Surgical; Financial Interests, Personal, Advisory Role: Myriad Genetics; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Other, Travel, accommodations, and expenses: Surgical. O.O. Yeku: Financial Interests, Personal, Advisory Board: TigaTx, Celldex, GIMV NV, hC Bioscience. J.F. Liu: Financial Interests, Institutional, Research Funding: Zentalis, Vigeo Therapeutics, Tesaro, Surface Oncology, Regeneron, Impact Therapeutics, GSK, CytomX Therapeutics, Clovis Oncology, Bristol Myers Squibb, AstraZeneca, Arch Oncology, Aravive, 2X Oncology; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Daiichi, Eisai, EpsilaBio, Genentech/Roche, GSK, Regeneron Pharmaceuticals Inc., Zentalis. B. Wang, S. Yoo, S. Govindraj, M. Zhu, J. Brouwer-Visser, M.J. Peterman, B. Barnes, I. Lowy, D. Knorr, 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. All other authors have declared no conflicts of interest.