TPS5638 Background: Low grade serous ovarian cancer (LGSOC) typically has a poor response to chemotherapy, presenting an unmet need for efficacious novel therapies that remain tolerable. Mucin 16 (MUC16) is a cell surface glycoprotein that is highly expressed in ovarian cancers, including LGSOC, and has been identified as a potential therapeutic target. Ubamatamab, a MUC16 × cluster of differentiation 3 bispecific antibody, bridges MUC16+ tumor cells and T cells through a major histocompatibility complex-independent mechanism, promoting cytotoxicity. In a first-in-human study (NCT03564340), ubamatamab demonstrated an acceptable safety profile and durable clinical activity in recurrent ovarian cancer, including LGSOC, which has particularly high MUC16 expression on tumor cells. Here, we describe an LGSOC-specific expansion cohort. Methods: In the LGSOC-specific cohort, patients who have received prior platinum-containing therapy (no maximum number of prior therapies) and whose disease has relapsed or progressed after the most recent line of therapy will receive ubamatamab 800 mg intravenously (IV) once every 3 weeks (Q3W). Prior to Q3W dosing of ubamatamab, patients will receive once-weekly step-up dosing to mitigate the risk of cytokine release syndrome, as well as sarilumab 350 mg IV prophylaxis on Day 1. Utilizing a Simon two-stage design, 20 patients will initially be enrolled in this cohort, expanding to 50 if there are ≥3 objective responses. The cohort may be further expanded to 100 patients if ≥14 objective responses (28%) are observed in the first 50 patients. The primary endpoint is objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints include safety, pharmacokinetics, patient-reported outcomes and further efficacy assessments. As of January 5, 2026, 6 patients with LGSOC have initiated ubamatamab treatment. Findings from this study will clarify the therapeutic potential of targeting MUC16 in LGSOC. Clinical trial information: NCT03564340 .
Nieuwenhuysen et al. (2026) studied this question.