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

• DOI: 10.1016/j.iotech.2023.100599
• Publication Date: 2023-12-08T11:09:03Z
• Authors: I.S. Winer; R.E. O'Cearbhaill; S. Bouberhan; J.L. Hays; R.M. Wenham; D.R. Roque; O.O. Yeku; J.F. Liu; B. Wang; S-Y. Yoo; S. Govindraj; M. Zhu; J. Brouwer-Visser; M.J. Peterman; B. Barnes; I. Lowy; D. Knorr; T.S. Uldrick; E.A. Miller
• Keywords: Interquartile range; Tolerability

REGN5668 (R5668) is a mucin16 (MUC16) x CD28 bispecific antibody (bsAb). R5668 provides "signal 2" T-cell costimulation through in the presence of MUC16 tumor antigen. bispecifics augment anti-tumor activity anti-PD-1 monoclonal Ab cemiplimab (cemi) preclinical studies. We present phase 1 dose-escalation results intravenous (IV) combined with cemi patients (pts) recurrent platinum-experienced ovarian cancer (OC). Pts received weekly IV at dose range 0.3-300 mg. Cemi 350 mg every 3 weeks was added beginning Day 21-28. Primary endpoints were safety and PK. Secondary included confirmed objective response rate (RECIST 1.1) CA-125 (Gynecologic Cancer InterGroup). Multiplex cytokine profiling exploratory. 28 pts enrolled; 22 (79%) ≥1 cemi. Median number prior therapies 3.5 (range 1−10). duration exposure 7.5 1.9-39.0) 6.1 (2.4−36.0) weeks, respectively. Fatigue (32%), nausea (29%), pain (18%) most common treatment-related adverse events (TRAEs). Infusion-related reactions/cytokine release syndrome (all Grade [G]1/2) occurred 14% pts. One pt had G≥3 TRAE (fatigue). There no resulting death or study drug discontinuation. No DLTs observed opening next cohort (1000 mg) planned. Across all treated to date, partial (-59% target lesion reduction from baseline) observed, both single 300 6 (21%) stable disease. dose-dependent increase between QW dosing. Cytokine analyses revealed apparent elevations after dosing, while upon addition, slight increases IFNγ IP10 observed. In heavily pretreated OC pts, an acceptable profile, low rates CRS, early + escalation ubamatamab (MUC16xCD3 bsAb) ongoing.