Phase I Safety Run‑In and Phase II Efficacy Study of Ubamatamab in Combination Therapy as Salvage Treatment for Poor‑Response Ovarian Cancer

The primary objective is to assess the safety profile of ubamatamab in combination with carboplatin, paclitaxel, and bevacizumab during the phase I safety run‑in and to determine antitumor efficacy in the subsequent phase II expansion in patients with poor‑prognosis ovarian cancer refractory to first‑line chemotherapy. Safety evaluation will inform dose‑limiting toxicities and tolerability, while efficacy assessment will quantify objective response rates and progression‑free survival, endpoints critical for establishing the regimen as a salvage therapeutic option. Secondary objectives include:

• Evaluation of safety throughout the entire treatment course.
• Evaluation of efficacy throughout the entire treatment course.

The sponsor did not provide information on the total number of participants. The trial enrolled adult female patients (≥ 18 years) with advanced stage III or IV disease, specifically those with high‑grade epithelial ovarian carcinoma (including serous, endometrioid, or carcinosarcoma with ≥30 % epithelial component), primary peritoneal, or fallopian‑tube carcinoma that had undergone 3–4 standard neoadjuvant carboplatin‑paclitaxel cycles and exhibited both poor chemotherapeutic response (standardized KELIM < 1.0) and incomplete interval cytoreductive surgery. Eligible individuals required adequate renal, hepatic, cardiac, and bone‑marrow function, an ECOG performance status of 0 or 1, a life expectancy of at least three months, and availability of tumor tissue for translational research. Selection was based on histologic confirmation, measurable disease per RECIST 1.1, and documented BRCA/HRD status (or planned testing). General health criteria ensured participants could tolerate study procedures, while no specific dietary or physical‑activity restrictions were stipulated beyond the ability to comply with protocol visits and treatments.

The study is an open‑label, non‑randomized Phase I/II trial evaluating ubamatamab in combination with carboplatin, paclitaxel, and bevacizumab as salvage therapy for ovarian cancer that responded poorly to first‑line chemotherapy. After an initial screening visit to confirm eligibility, participants receive a baseline assessment followed by intravenous administration of the study drugs every 21 days. The safety run‑in (Phase I) monitors dose‑limiting toxicities during the first four weeks, while the efficacy expansion (Phase II) continues treatment until disease progression, unacceptable toxicity, withdrawal of consent, death, or completion of the planned treatment course, which is expected to last up to approximately 12 months. Study visits include clinical and laboratory evaluations at each treatment cycle, radiologic assessments after three cycles to determine the objective response rate, and regular follow‑up visits until the end‑of‑study visit, which occurs after the final treatment or early discontinuation. Early termination criteria comprise grade ≥ 3 treatment‑emergent adverse events, failure to meet dose‑limiting toxicity thresholds, or disease progression as defined by RECIST 1.1. The overall trial recruitment period spans from April 2026 to April 2030.

The investigational product is Ubamatamab, supplied as a sterile solution for injection for intravenous administration. It is administered on a per‑cycle basis in a 21‑day schedule; the exact dose level and duration are defined by the dose‑escalation schema of the safety run‑in phase. Infusions are performed under clinical supervision with vital‑sign monitoring before, during, and after the administration.

The chemotherapy backbone includes Carboplatin, given intravenously on day 1 of each treatment cycle. Dosing is calculated according to body surface area using the area‑under‑the‑curve (AUC) method as specified in the protocol, and the infusion is completed over the recommended time frame to ensure tolerability.

Paclitaxel is administered intravenously on day 1 of each cycle, following standard pre‑medication to mitigate hypersensitivity reactions. The dose is expressed in milligrams per square meter of body surface area and is infused over the prescribed duration per cycle.

Bevacizumab is provided as an intravenous infusion on day 1 of each cycle, with dosing based on body weight (milligrams per kilogram). The infusion is delivered according to the recommended rate, and subsequent cycles follow the same schedule.

Filgrastim is used as supportive care to reduce the risk of neutropenia. It is administered intravenously (or subcutaneously as per local practice) beginning 24 hours after chemotherapy and continued daily until the absolute neutrophil count reaches the predefined threshold.

All administered agents are recorded in the study drug log, and compliance is monitored through infusion documentation, dosing checklists, and periodic review of laboratory parameters. Any deviations from the prescribed schedule are reported in accordance with the trial’s pharmacovigilance procedures.

Efficacy will be evaluated using several radiographic and clinical endpoints. The primary efficacy endpoint is the objective response rate (ORR), defined as the proportion of patients achieving a complete (CR) or partial response (PR) as the best overall radiological response after three cycles of ubamatamab combined with carboplatin, paclitaxel, and bevacizumab. Secondary efficacy endpoints include ORR over the entire treatment period, disease control rate (DCR) (CR, PR, or stable disease), duration of response, progression‑free survival (PFS), overall survival (OS), progression‑free survival during subsequent line of treatment (PFS‑ST), and the proportion of patients undergoing late cytoreductive surgery after three cycles, with the subset achieving complete macroscopic resection.

Radiological assessments will be performed using contrast‑enhanced imaging evaluated according to RECIST 1.1 criteria. Baseline scans will be obtained prior to the first dose, followed by imaging after the third treatment cycle to determine the primary ORR, and then at regular intervals throughout the study to monitor disease status for secondary endpoints. Responses will be classified as CR, PR, stable disease, or progressive disease. Duration of response will be calculated from the date of first documented response to the date of documented progression or death. PFS and PFS‑ST will be measured from the start of treatment (or subsequent line) to the first documented progression or death, with censoring at the last evaluable assessment. OS will be measured from treatment initiation to death from any cause, with censoring for patients alive at the time of analysis. Surgical outcomes will be recorded after the specified three‑cycle period, documenting the rate of late cytoreductive surgery and the rate of complete macroscopic resection among those operated.