Ubamatamab (REGN4018) is a mucin 16 x cluster of differentiation 3 (MUC16xCD3) bispecific antibody that promotes T cell–mediated cytotoxicity by binding MUC16-expressing ovarian cancer (OC) cells and CD3+ T cells. We present safety, efficacy and pharmacokinetic (PK) modelling from a first-in-human study of ubamatamab (NCT03564340).
Patients (pts) with recurrent platinum-experienced OC received ubamatamab 0.3–800 mg intravenously weekly (QW) after initial step-up dosing. Primary endpoints were safety and PK. Secondary and exploratory endpoints included objective response rate per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, disease control rate (a response or stable disease) and cancer antigen 125 (CA-125) response per Gynecological Cancer InterGroup criteria.
78 pts received ubamatamab 0.3–800 mg without reaching maximal tolerated dose. Median number of prior therapies was 4.5 (range 1–17). Median ubamatamab exposure was 12 (range 1–117) weeks. Commonest treatment-emergent adverse events (TEAEs) were cytokine release syndrome (73.1%, all Grade 1/2) and pain (87.2%), primarily occurring in Weeks 1–2 of step-up dosing. Commonest Grade ≥3 TEAEs were anemia (24.4%) and abdominal pain (20.5%). Objective responses were observed between 20–800 mg. In 42 pts receiving ≥1 full dose of ≥20 mg, ORR was 14.3% (95% CI, 5.4–28.5), disease control rate was 57.1% (41–72.3), and median duration of response was 12.2 months. 23.8% of pts (12.1–39.5%) had a CA-125 response. Serum ubamatamab concentrations increased dose proportionally. No apparent dose-response relationship was observed from 20–800 mg for safety or efficacy. PK modelling supported the selection of 250 and 800 mg every-3-weeks (Q3W) regimens for Phase 2, as both regimens had a maximum concentration (Cmax) below the Cmax of 800 mg QW, and trough concentration (Cmin) above that of the minimal effective dose (20 mg QW).
Ubamatamab resulted in an acceptable safety profile and durable responses in a heavily pretreated OC population across a wide dose range. A randomised Phase 2 expansion trial with initial step-up dosing followed by Q3W dosing has been initiated.
ClinicalTrials.gov: NCT03564340
Editorial support was provided by Rachel McGrandle of Prime Medica, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc.