523MO Ubamatamab (REGN4018, MUC16xCD3 bispecific antibody) monotherapy in patients with recurrent ovarian cancer (OC): Phase I dose-escalation analysis

Ubamatamab is a mucin-16 x cluster of differentiation 3 (MUC16xCD3) bispecific antibody that promotes T cell–mediated cytotoxicity by binding MUC16-expressing OC cells and CD3+ T cells. We present safety, pharmacokinetics (PK) and efficacy from a first-in-human Phase 1 study of ubamatamab (NCT03564340). Patients with advanced platinum-experienced OC and elevated serum cancer antigen 125 were administered ubamatamab monotherapy intravenously weekly at a dose range of 0.1–800 mg after initial step-up dosing. Dose escalation followed a modified 3+3 design. Primary endpoints were safety and PK. Secondary endpoints included preliminary estimate of objective response rate (ORR) per RECIST 1.1. 78 patients received ubamatamab; median number of prior therapies was 4.5 (range 1–17). Median duration of exposure was 12 (range 0.4–117) weeks. The most common treatment-emergent adverse events (TEAE) were cytokine release syndrome (73.1%, all Grade 1/2) and pain (87.2%) that primarily occurred during Weeks 1–2 of initial step-up dosing. The most common Grade ≥3 TEAEs were anaemia (23.1%) and abdominal pain (19.2%). Objective responses were observed between 20–800 mg doses (n=50). ORR of those receiving ≥1 full dose (n=42) was 14.3% (95% CI 5.4–28.5) and disease control rate (DCR) was 57.1% (41.0–72.3). Median duration of response was 12.2 months. In a subset of these patients without baseline visceral metastases (n=29) ORR was 20.7% (8.0–39.7) and DCR was 72.4% (52.8–87.3). Exploratory analysis of patients with >75% of tumour cells with 2+ baseline MUC16 immunohistochemical staining and ≥1 dose of ≥20 mg (n=13) showed ORR of 30.8% (9.1–61.4), and DCR 61.5% (31.6–86.1). Serum ubamatamab concentrations increased dose-proportionally. No definitive dose-response relationship was observed in safety or efficacy between 20–800 mg. Ubamatamab safety profile was acceptable with evidence of durable responses in this heavily pretreated population with OC across a wide dose range. Based on data from this study, a randomised Phase 2 expansion has been initiated.