A phase 1/2 study of REGN5668, a MUC16×CD28 costimulatory bispecific antibody, in combination with other targeted therapies, in patients with recurrent ovarian or endometrial cancer: Trial in progress update.

TPS5639 Background: REGN5668 and ubamatamab are immunoglobulin G4-based bispecific antibodies that bridge mucin 16 (MUC16)+ tumor cells to T-cell–expressed cluster of differentiation (CD)28 and CD3, respectively, to stimulate T-cell cytotoxicity. Cemiplimab (anti–programmed cell death-1 PD-1) and fianlimab (anti-lymphocyte activation gene 3 LAG-3) are monoclonal antibodies that target inhibitory T-cell immune checkpoints. This first-in-human, multicenter, Phase 1/2 trial (NCT04590326) will assess safety, tolerability, pharmacokinetics (PK), and antitumor activity of REGN5668 + cemiplimab ± fianlimab (Module 1) or ubamatamab (Module 2) in patients with platinum-resistant recurrent ovarian cancer (OC) or endometrial cancer (EC). In Module 1, REGN5668 dose escalation is complete (n=58), demonstrating early clinical activity and only 1 dose-limiting toxicity, a treatment delay of >7 days due to Grade 1 dry eye. Here we present details of additional dose escalation and expansion modules currently enrolling patients. Methods: Module 1 dose expansion will evaluate REGN5668 + cemiplimab ± fianlimab in OC and EC cohorts. In the OC cohort, patients will receive REGN5668 + cemiplimab + fianlimab, with an initial 12-patient safety lead-in. In the EC cohort, patients will receive REGN5668 + cemiplimab; an additional EC cohort may be added to evaluate REGN5668 + cemiplimab + fianlimab. Each cohort will follow a Simon two-stage design. In stage 1, 20 patients will be enrolled; if there are ≥3 objective responses, stage 2 will proceed with enrollment of ≤50 patients. In Module 2, dose escalation will evaluate patients with OC receiving escalating doses of REGN5668 + ubamatamab using a Bayesian optimal interval design. Patients may also receive sarilumab to mitigate the risk of cytokine release syndrome. Key OC cohort eligibility criteria include histologically confirmed diagnosis of advanced epithelial OC (except carcinosarcoma), ≥1 prior line of platinum-based systemic therapy, and disease relapse or progression during most recent therapy. Key EC cohort eligibility criteria include histologically confirmed diagnosis of EC with disease recurrence or progression after anti–PD-1 therapy and platinum-based chemotherapy, ≤4 prior lines of systemic therapy, ≥30 days since anti–PD-1 therapy administration, and ≥25% of tumor cells that are MUC16+. Primary endpoints are safety and PK in dose escalation, and objective response rate (ORR) in dose expansion. Secondary endpoints include ORR (Module 2 dose escalation), safety and PK (Module 1 dose expansion), further efficacy outcomes, and immunogenicity (all cohorts). Module 1 dose expansion has opened, with the first two patients enrolled. In Module 2, dose escalation of REGN5668 has progressed through multiple dose levels; enrollment is ongoing. Clinical trial information: NCT04590326 .