KEY TAKEAWAYS
- The phase 1 and 2 trials aimed to assess safety and preliminary efficacy of R5668 + cemi combo dose-escalation for relapsed platinum-resistant OC.
- The primary endpoint was to evaluate safety and R5668 PK.
- The result demonstrated that the R5668 + cemi combo in heavily pretreated OC showed acceptable safety and low CRS.
- The ongoing dose escalation of R5668 in combination with either cemi or ubamatamab (MUC16xCD3 bsAb) is in progress.
REGN5668(R5668), a bispecific antibody targeting mucin16 (MUC16) and CD28 bispecific antibody (bsAb), activates T cells via CD28 costimulation when encountering MUC16 tumor antigen. Preclinical studies suggest its synergy with the anti-PD-1 antibody cemiplimab (cemi).
In the phase 1 trial, Ira S. Winer and his research group explored the safety and preliminary efficacy of combining R5668 and cemi in patients (pts) with recurrent platinum-resistant ovarian cancer (OC).
The enrolled pts were administered intravenous R5668 weekly at doses ranging from 0.3 to 300 mg, with cemi (350 mg IV every 3 weeks) added between Day 21-28. The primary endpoint was to assess safety and R5668 pharmacokinetics (PK). The secondary endpoints encompassed confirmed objective response rate(ORR) (RECIST 1.1), CA-125 response (Gynecologic Cancer InterGroup), and exploratory multiplex cytokine profiling.
Among the 28 enrolled pts, 22 (79%) received at least one dose of cemi. The median number of prior therapies was 3.5 (range 1-10). The median duration of exposure to R5668 and cemi was 7.5 weeks (range 1.9-39.0) and 6.1 weeks (range 2.4-36.0).
The most common treatment-related adverse events (TRAEs) included fatigue (32%), nausea (29%), and pain (18%). Infusion-related reactions/cytokine release syndrome (all Grade [G]1/2) occurred in 14% of pts. One patient experienced a G≥3 TRAE (fatigue). There were no adverse events leading to death or discontinuation of the study drug. No dose-limiting toxicities (DLTs) were observed, and the next cohort (1000 mg) is planned to open.
Across all treated pts, one confirmed partial response (-59% target lesion reduction from baseline) and one CA-125 response were observed, both in a single patient at 300 mg. Stable disease was noted in 6 (21%) pts. A dose-dependent increase in R5668 exposure was observed between 1 mg and 300 mg IV QW dosing.
The Cytokine analyses revealed no significant elevations after R5668 dosing, while the addition of cemi resulted in slight increases in IFNγ and IP10
The result concluded that in 28 extensively treated OC pts, the combination of R5668 and cemi demonstrated favorable safety, minimal cytokine release syndrome (CRS), and promising early efficacy. The ongoing dose escalation trials for R5668 with cemi or ubamatamab (MUC16xCD3 bispecific antibody) is underway. This trial is sponsored by Regeneron Pharmaceuticals.
Source: https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/34
Clinical Trial: https://www.clinicaltrials.gov/study/NCT04590326
Winer IS, et al. “ REGN5668 (MUC16xCD28 bispecific antibody) with cemiplimab (anti-PD-1 antibody) in recurrent ovarian cancer: Phase 1 dose-escalation study”. Presented at ESMO IO 2023. (Abstract: 127P)
