Preliminary results from a phase I expansion study of ZG005, a bispecific antibody targeting TIGIT and PD-1, as monotherapy in patients with advanced solid tumors.

2611 Background: ZG005, a PD-1 and TIGIT dual-specific antibody, is a promising immunotherapy for tumors as blocking these two pathways could synergistically activate T cells and enhance the anti-tumor activity of NK cells. Partial results from the dose-escalation stage of this first-in-human (FIH) study were revealed at ASCO 2023, and here we present the preliminary results from the dose-expansion stage. Methods: After a dose-escalation stage, patients (subjects) with solid advanced tumors were enrolled into this dose-expansion stage. Subjects in each cohort were randomized 1:1 to receive ZG005 treatment of either RP2D from the dose-escalation stage (10 mg/kg Q3W or 20 mg/kg Q3W) by intravenous infusion. Efficacy was assessed primarily according to RECIST v1.1. Results: The dose-escalation stage was completed with 32 subjects enrolled and the dose-expansion stage is currently ongoing. As of December 25, 2023, a total of 68 subjects were treated with ZG005 as monotherapy, including 33 males (median age 60) and 35 females (median age 58), wherein 33 had received PD-1/PD-L1 inhibitors before enrollment. Three subjects with either pancreatic neuroendocrine cancer, intrahepatic cholangiocarcinoma, or cervical cancer were treated for more than 20 cycles. The subject with cervical cancer maintained PR status for more than 35 weeks. A total of 1 CR, 6 PR, and 28 SD cases were reported from the 57 efficacy evaluable subjects, among them 1 CR, 5 PRs, and 8 SDs from the 17 subjects with cervical cancer. A total of 43 TRAEs (43/68, 63.2%) were reported, of which 6 were ≥ grade 3, including 2 liver function abnormalities, 1 elevated γ-glutamyl- transferase, 1 unknown death, 1 hypertriglyceridemia and lipase elevation, and 1 elevation in both aspartate aminotransferase and blood bilirubin. SAEs occurred in 19 subjects, 3 events were related to ZG005, including 2 liver function abnormalities (1 was a DLT event), and 1 unknown death. The death event occurred in one female, who received only one dose of ZG005, and the cause of her death was most likely due to poor underlying condition. The C max and AUC increased approximately in dose proportion. Conclusions: ZG005 has demonstrated a tolerable safety profile and encouraging anti-tumor activity during the FIH study. Expansion cohorts in specific advanced solid tumors are underway to warrant further development. Clinical trial information: CTR20220021.