Preliminary results of ZG005, a bispecific antibody targeting PD-1 and TIGIT, in combination with chemotherapy with or without bevacizumab as first-line treatment for advanced cervical cancer.

5529 Background: ZG005, a PD-1 and TIGIT dual-specific antibody, is a promising immunotherapy for tumors. By blocking both pathways, it can synergistically activate T cells and enhance the anti-tumor activity of NK cells. This report presents the results for the combination of ZG005 and the chemotherapy with or without bevacizumab as a first-line systematic treatment in patients (pts) with advanced cervical cancer. Methods: ZG005-003 was a multicenter, open-label, phase I/II clinical trial. In the Part 1, the escalating doses were 10 mg/kg and 20 mg/kg. In the Part 2, pts were randomized at 1:1 ratio to receive ZG005 at 10 mg/kg or 20 mg/kg in combination with the standard chemotherapy (paclitaxel [175 mg/m 2 ] plus carboplatin [AUC 5] or cisplatin [50 mg/m 2 ]), with or without bevacizumab (15 mg/kg) every 3 weeks for six cycles, followed by the maintenance therapy of ZG005 with or without bevacizumab for up to 2 years. Safety and efficacy (per RECIST v1.1) were assessed. Results: As of December 19, 2024, the Part 1 had completed and the Part 2 was ongoing, a total of 41 pts had been enrolled for the both Parts, with 12 pts in Part 1 and 29 pts in Part 2. The median age was 54 years, and 87.8% of pts were squamous carcinoma. 53.7% of pts received bevacizumab during the trial. No dose-limiting toxicity (DLT) were observed during the Part 1. Among all the 41 pts, 31 (75.6%) experienced treatment-related adverse events (TRAEs) which attribute to ZG005. Most TRAEs were grade 1-2, while 12 pts (29.3%) reported grade 3 or higher TRAEs. There was no treatment discontinuation or death due to TRAEs. Only one serious adverse event (SAE) of bilateral lung pneumonia in the 10 mg/kg group was assessed related to ZG005 by the investigator. No ZG005-related SAE was reported in the 20 mg/kg group. Of the 28 pts evaluable for efficacy, 13 on 10 mg/kg and 15 on 20 mg/kg, the unconfirmed overall response rates (ORR) was 69.2% for the 10 mg/kg group, and 80.0% for the 20 mg/kg group. Conclusions: ZG005 in combination with the chemotherapy, with or without bevacizumab, demonstrated favorable safety and tolerability profiles at both 10 mg/kg and 20 mg/kg dosages. Additionally, this regimen exhibited a significant antitumor activity in first-line cervical cancer pts, with the 20 mg/kg dose group showing a notably better efficacy in comparison with the 10 mg/kg dose group. Clinical trial information: NCT06241235 .