Introduction Ubamatamab (REGN4018; mucin16 [MUC16] x CD3 bispecific antibody) promotes T-cell-mediated killing of ovarian cancer (OC) cells in preclinical studies. This activity is enhanced by the anti-PD-1 antibody cemiplimab. We present first-in-human ubamatamab +/- cemiplimab dose escalation results in recurrent OC.

Methods Patients with recurrent platinum-experienced OC received weekly intravenous ubamatamab 0.3–800 mg after step-up dosing. Patients in combination cohorts received intravenous cemiplimab 350 mg every 3 weeks beginning Day 29–36. Endpoints assessed safety (primary), clinical activity (secondary), and correlatives of tumor MUC16 immunohistochemistry and serum CA125 (exploratory).

Results 109 patients (N=74 monotherapy/N=35 combination) were enrolled. Median number of prior therapies was 5 (range 1–17). Commonest treatment-related adverse events of any grade occurred in the first 4 weeks of treatment, including pain (75.2%; Grade 1–2 56.9%; Grade 3 18.3%) and cytokine release syndrome (72.5%; all Grade 1–2) (table 1), with few of these events after addition of cemiplimab. In efficacy analyses (n=42 monotherapy/n=22 combination), ORR was 14.3%/18.2%, median duration of response was 13.7/8.3 months, and CA125 response (GCIG criteria) was 31.0%/22.7%. All patient tumors expressed MUC16 by immunohistochemistry. Responses with ubamatamab monotherapy were observed across a range of MUC16 expression levels. Response rates and PFS increased with increasing number and intensity of MUC16+ cells. CA125 response was associated with improved PFS (monotherapy: hazard ratio 0.35; 95% CI 0.17–0.72).

Conclusion/Implications Ubamatamab +/- cemiplimab demonstrated acceptable safety and evidence of clinical activity in heavily pretreated OC. An ongoing randomised Phase 2 study is evaluating ubamatamab alone and with cemiplimab.