A phase II efficacy and safety study of HB0025 (a PD-L1/VEGF bispecific antibody) in combination with chemotherapy as first-line treatment for advanced or recurrent endometrial cancer.

5602 Background: HB0025, developed by Huaota, is a novel anti-PD-L1/VEGF bispecific antibody, with VEGFR1D2 linked at the N-terminal of anti- PD-L1 antibody. Carboplatin and paclitaxel (CP) alone or in combination with PD-(L)1 is a recommended regimen for first-line treatment of advanced endometrial carcinoma (EC) that the ORRs were 40%-68% regardless MMR status. This study assesses the efficacy and safety of HB0025 in combination with chemotherapy in EC patients. Methods: This open-label, multi-center phase II study of HB0025 with CP in primary advanced (stage III or IV) or first recurrent EC. Patients received 20mg/kg HB0025 every 3 weeks with CP for 4-6 cycles, followed by maintenance therapy with HB0025. The primary endpoint was objective response rate (ORR), assessed by RECIST v1.1. Results: As of Dec 25, 2024, 39 patients were enrolled. The median age was 59.0 years (range, 32.0-71.0). The median follow-up time was 3.3 months (range: 0.6-6.9). 31 patients had at least one post-baseline tumor assessment. The ORR and disease control rate (DCR) were 83.9% (26/31) and 100.0% (31/31), respectively. The ORR were 84.0% (21/25) in pMMR patients and 100.0% (4/4) in dMMR patients. Median duration of response (DOR) and progression-free survival (PFS) were not reached. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 18 patients (46.2%), The most common grade ≥3 TRAEs (≥10%) included neutropenia (30.8%), leukopenia (15.4%), thrombocytopenia (10.3%). Any-grade immune-related adverse events (irAEs) only occurred in 2 patients (5.1%). Treatment-related serious adverse events (SAEs) were observed in 5.1% (2/39) of patients. No TRAE led to treatment discontinuation or death. Any-grade hemorrhage events occurred in 7 (17.9%) patients which were all grade 1 in severity. Conclusions: HB0025 in combination with chemotherapy demonstrated promising anti-tumor efficacy with good safety profile. Regardless MMR status, ORR with HB0025 plus CP improved significantly over histologically reported data. A multicentre, randomized, double-blind, controlled phase III trial will commence in 2025. Clinical trial information: NCT06758557 .