Preliminary results of ZG005, a bispecific antibody targeting PD-1 and TIGIT, as monotherapy in patients with advanced cervical cancer.

5528 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. Preliminary results of this first-in-human (FIH) study were presented at ASCO 2023 and ASCO 2024. Here, we report the efficacy and safety results in patients with advanced cervical cancers. Methods: Following the dose-escalation phase, patients with specified tumor types were enrolled into dose-expansion stage. Within each tumor type cohort, subjects were randomized 1:1 to receive ZG005 10 mg/kg Q3W or 20 mg/kg Q3W by intravenous infusion. Efficacy was assessed by both the investigator and the independent radiology committee (IRC) according to RECIST v1.1. Results: As of December 05, 2024, a total of 55 patients with advanced cervical cancer had been randomized to receive at least one dose of ZG005 10 or 20 mg/kg. The median age was 52.0 years. Of these patients, 98.2% had failed to at least one prior line of therapy, and 24.7% had previously received immune checkpoint inhibitor (ICI) treatments. 87.3% patients were squamous cell carcinoma, 9.1% adenocarcinoma and 3.6% adenosquamous carcinoma. Among the total 22 patients on the 20 mg/kg group who hadn't treated any prior ICI treatments before, 3 achieved a complete response (CR) and 6 partial responses (PR) per the IRC's assessments. The confirmed objective response rate (ORR) was 40.9%, and the disease control rate (DCR) was 68.2%. The median progression free survival (mPFS) has not yet been reached. Among the 55 patients for the safety analyses, 46 (83.6%) reported treatment related adverse events (TRAEs), with 5 (9.1%) grade 3-4, including one patient each with hypocalcemia, myositis, rash, hypertension and anemia. Serious adverse events (SAEs) occurred in 8 subjects (14.5%), with one myositis case (1.8%) was the only SAE related to ZG005 and also the sole TRAE that led to treatment discontinuation. No death was attributed to ZG005. Grade 3-4 Immune-related adverse events (irAEs) were observed in 4 patients (7.3%), including myositis, rash, hypertension and anemia. No new safety signals were observed compared with other ICIs. Conclusions: ZG005 has demonstrated a tolerable safety profile and promising anti-tumor activity at the 20 mg/kg dose as monotherapy in patients with advanced cervical cancer. Clinical trial information: NCT06233293 .