RegeNovar: A phase I/II study of ubamatamab plus carboplatin, paclitaxel, and bevacizumab as salvage therapy in ovarian cancer with poor response to first-line chemotherapy.

TPS5640 Background: Patients with advanced epithelial ovarian cancer (EOC) treated with neoadjuvant platinum-based chemotherapy who are not amenable to complete interval cytoreductive surgery (ICS) due to poor chemosensitivity—defined by a CA-125 KELIM score <1.0—have a particularly poor prognosis, with approximately 20% 5-year overall survival. Ubamatamab is a human IgG4-based bispecific antibody targeting MUC16 (CA-125–expressing ovarian cancer cells) and CD3+ T cells and has demonstrated clinical activity in platinum-resistant recurrent ovarian cancer (Lee et al, Proc ESMO 2025). We hypothesize that adding ubamatamab to standard carboplatin–paclitaxel–bevacizumab may enhance tumor response and improve surgical resectability in patients with advanced high-grade EOC with poor chemosensitivity and disease not amenable to complete ICS after initial neoadjuvant chemotherapy. Methods: RegeNovar (EuCT 2025-524232-20-00) is an academic, multicenter phase I–II trial enrolling patients with stage III–IV high-grade EOC who, after 3–4 cycles of standard neoadjuvant carboplatin–paclitaxel administered every 3 weeks, present two poor prognostic features: (1) unfavorable standardized KELIM score <1.0, and (2) disease considered not amenable to complete ICS. The trial includes two sequential parts: (i) a phase I safety run-in to evaluate the safety of ubamatamab in combination with carboplatin–paclitaxel–bevacizumab and confirm the recommended phase II dose (RP2D); and (ii) a phase II efficacy part assessing the antitumor activity of this combination. Patients receive carboplatin AUC5 ; paclitaxel 175 mg/m²; and bevacizumab 15 mg/kg Q3 weeks for three cycles. Ubamatamab is administered with weekly step-up dosing during cycle 1, followed by a fixed dose of 800 mg Q3 weeks during cycles 2 and 3. Feasibility of complete late cytoreductive surgery is evaluated after three cycles of the study regimen. Subsequent maintenance treatment consists of olaparib plus bevacizumab for patients with BRCA-mutated or HRD-positive tumors, or ubamatamab plus bevacizumab for up to 15 months in patients with HRD-negative tumors. The primary endpoint of phase I is safety, including treatment-related adverse events (NCI CTCAE v6.0), DLT within the first 4 weeks, and RP2D determination using a BOIN design targeting a DLT probability ≤28%. The primary endpoint of phase II is the objective response rate (ORR) after three cycles per RECIST 1.1 (H0 5%, H1 30%, one-sided α=5%, power=80%). Total 31 to 43 patients are required, depending on potential need for dose de-escalation. Secondary endpoints include ORR, duration of response, disease control rate, rate of late cytoreductive surgery, PFS, OS, and progression-free survival during subsequent therapy. The trial is sponsored by ARCAGY-GINECO, conducted in 12 French centers, and funded by Regeneron. Clinical trial information: EuCT 2025-524232-20-00.