First-in-human phase 1/2 study of ubamatamab, a MUC16xCD3 bispecific antibody, administered alone or in combination with cemiplimab in patients with recurrent ovarian cancer

TPS5624 Background: Mucin-16 is a cell surface glycoprotein that is overexpressed in epithelial ovarian cancer (OC). Ubamatamab (REGN4018) is a mucin-16 x cluster of differentiation 3 (MUC16xCD3) bispecific antibody that promotes T cell–mediated cytotoxicity by facilitating contact between cancer cells and T cells. In mouse model studies, ubamatamab demonstrated dose-dependent antitumor activity against MUC16-expressing OC tumor cells. 1 Cemiplimab is an anti–programmed cell death-1 monoclonal antibody. In a Phase 1 study (NCT03564340) in patients with recurrent OC, ubamatamab monotherapy demonstrated an acceptable safety profile, durable clinical activity across a range of doses between 20 mg and 800 mg intravenous (IV) weekly (as measured by RECIST and cancer antigen 125 [CA-125] response rates), and linear pharmacokinetics up to 800 mg IV weekly. 2 These clinical data support further evaluation of a once every 3-week (Q3W) regimen of ubamatamab alone and in combination with cemiplimab. The study is currently recruiting patients to combination dose escalation, monotherapy dose expansion, and the randomized Phase 2 cohort. Methods: In Phase 2, up to 150 patients with advanced platinum-resistant OC and elevated serum cancer antigen-125 will be randomized to three arms (1:1:1) to receive ubamatamab 250 mg IV Q3W or 800 mg IV Q3W as monotherapy, or ubamatamab 250 mg IV Q3W in combination with cemiplimab 350 mg Q3W. All arms will include weekly step-up dosing of ubamatamab (1 mg week 1, 20 mg week 2, and full dose weeks 3 and 4) to limit risk of cytokine release syndrome prior to proceeding to Q3W dosing. Expansion cohorts will use a Simon 2-stage study design, with an interim analysis after the first 20 patients. Any arm with ≥3 objective responses will be expanded to 50 patients. The primary objective of the dose expansion phase is to assess the preliminary efficacy of ubamatamab as monotherapy or in combination with cemiplimab, separately by cohort. Secondary objectives include characterization of the safety profile by cohort, and the pharmacokinetics of ubamatamab alone or in combination with cemiplimab, as well as patient-reported outcomes for all cohorts. In this dose expansion phase the primary endpoint will be the objective response rate for each arm as defined by RECIST 1.1 criteria. Secondary endpoints include evaluation of duration of response and progression-free survival as well as further evaluation of safety and pharmacokinetics. Exploratory endpoints include evaluation of baseline tumor MUC16 immunohistochemistry expression and other biomarkers as predictors of response. The impact of ubamatamab on quality of life and physical functioning will also be assessed. References: 1. Crawford A et al. Sci Transl Med. 2019;11:eaau7534. 2. Annals of Oncology (2022) 33 (suppl_7): S235-S282. 10.1016/annonc/annonc1054. Clinical trial information: NCT03564340 .