Introduction Ubamatamab (REGN4018) is a MUC16xCD3 bispecific antibody that promotes T cell-mediated cytotoxicity by facilitating contact between cancer cells and T cells. In a Phase 1 study (NCT03564340) in patients with recurrent ovarian cancer (OC), ubamatamab monotherapy demonstrated an acceptable safety profile and durable clinical activity at doses of 20 mg to 800 mg IV weekly (by RECIST and CA-125 response rates), and linear pharmacokinetics up to 800 mg IV weekly.

Methods In Phase 2, up to 150 patients with advanced platinum-resistant OC and elevated serum CA-125 will be randomized 1:1:1 to IV Q3W treatment: ubamatamab 250 mg; ubamatamab 800 mg; or ubamatamab 250 mg plus cemiplimab 350 mg (figure 1). All treatment 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 before proceeding to Q3W dosing. Expansion cohorts will use a Simon 2-stage study design, with interim analysis after 20 patients. Any arm with ≥3 objective responses will be expanded to 50 patients. The primary endpoint for each treatment arm is ORR per RECIST 1.1 criteria. Secondary endpoints include DOR, PFS, safety, and pharmacokinetics of ubamatamab with/without cemiplimab. Exploratory endpoints include evaluation of baseline tumor MUC16 expression and other biomarkers as predictors of response. The impact of ubamatamab on QOL and physical functioning will be assessed.

Current Trial Status The study is currently recruiting patients to combination dose escalation, monotherapy dose expansion, and the randomized Phase 2 cohort.

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Abstract TP020/#1513 Figure 1

(A) Phase 1 dose escalation and Phase 2 dose expansion including randomized Phase 2 cohort and (B) study schema for randomized Phase 2 cohort