Translational findings support regimen selection for first‐in‐human study of ubamatamab (<scp>MUC16</scp> × <scp>CD3</scp> bispecific antibody) in patients with recurrent ovarian cancer

Abstract Ubamatamab, a Mucin 16 (MUC16) × cluster of differentiation 3 (CD3) bispecific antibody that promotes T‐cell‐mediated cytotoxicity of MUC16‐expressing cells, is being investigated for the treatment of ovarian cancer. Intravenous administration of ubamatamab, with or without the anti‐programmed cell death‐1 inhibitor cemiplimab, is being evaluated in a first‐in‐human study in patients with recurrent ovarian cancer. In vitro cytotoxicity and cytokine data and projected ubamatamab human pharmacokinetic (PK) profiles scaled with monkey PK parameters enabled starting‐dose selection in humans. Mouse tumor regression studies identified ubamatamab effective concentrations. Preclinical and clinical PK, cytokine, safety, and efficacy data from dose escalation were integrated to determine expansion regimens. A starting dose of 0.1 mg was selected, which showed acceptable safety in patients. A step‐up dosing approach was used to effectively manage cytokine release syndrome. Mouse tumor regression models suggested an ubamatamab efficacious concentration range of 0.4–50 mg/L, consistent with clinical activity observed at ubamatamab trough concentrations ≥5 mg/L. Integrating preclinical and clinical data determined a target trough concentration range of 5–30 mg/L, which supports evaluation of ubamatamab 250 mg with or without cemiplimab and 800 mg monotherapy once every 3 weeks in expansion cohorts. Preclinical data (cytokine release, tumor regression, monkey PK) had translational value in supporting regimen selection in dose escalation and subsequently in dose expansion after integration with patient data from dose escalation.