1500 A phase II trial of bispecific antibody Q-1802 in patients with relapsed or refractory solid tumors

<h3>Background</h3> Claudin-18 isoform 2 (CLDN18.2) is a tight-junction protein, which expressed in normal gastric mucosa cells, or ectopically expressed on several types of solid tumor cells surface during malignant transformation, including lung, esophageal, pancreatic and gastric tumor cells. Increased expression and mis-location of CLDN18.2 in tumor cells suggested it as a tumor specific antigen and a possible target for therapy. Q-1802 is a humanized bispecfic antibody drug that targets CLDN18.2 and immune checkpoint PD-L1. <h3>Methods</h3> His study is a multi-center, single-arm, open-label design. Over 50 adult patients with advanced or metastatic solid tumors, were planning to be recruited. Q-1802 was administered intravenously to patients Q2w on a 14-day treatment cycle. Patients had been received Q1802 at dose of 10 mg/kg or 20 mg/kg in combination with CAPOX. Cycles are repeated until loss of clinical benefit, unacceptable toxicity or consent withdrawal. The primary endpoint is confirmed objective response rate (ORR) per RECIST v1.1. include progression free survival (PFS), disease control rate (DCR), duration of response (DOR), overall survival (OS) and adverse event (AE). <h3>Results</h3> As of Sep 1, 2024 (date cut off), 33 patients were enrolled totally, including 24 male (72.7%) and 9 female (27.3%). The median age of patients was 60 years old, ranged from 27 to 74. Among the patients, 8 patients (24.2%) were CLDN18.2 middle-level expression, while 25 patients (75.8%) were CLDN18.2 high level expression. 11 patients had already received surgical treatment, and 6 patients had ever received chemotherapy, while no one received immunotherapy, targeted therapy, or biological therapy before. All the patients have suffered from metastasis and received at least 2 cycles of trial treatment. So far, the results from 24 patients, including 20 patients in low dose group (10mg/kg) and 4 patients in high dose group (20mg/kg), were obtained and suitable for medical evaluation. In 10mg/kg group, 14 patients (70%) were partial response (PR), and 6 patients (30%) were stable disease (SD); the AE of Grade 3 was metabolic disease (6.9%), gastrointestinal diseases (24.1%), immune disease (3.4%), infection disease (3.4%). In 20mg/kg group, PR and SD was 50%, respectively; the AE of Grade 3 was gastrointestinal diseases (25%), leukopenia (25%), neutropenia (25%), lipase increase (25%), hyperamylasemia (25%). <h3>Conclusions</h3> The Preliminary results showed promising clinical efficacy in the patients, and demonstrated that Q-1802 has excellent anti-tumor activity. The expansion of phase II study is still in progress, and the survival effects are under follow up. <h3>Trial Registration</h3> This study for ClinicalTrials.gov identifier (NCT number): NCT04856150. <h3>Ethics Approval</h3> This study has been approved by Medical Ethics Committee of Peking University Cancer Hospital with approval number 2023YW14-ZY01; and written informed consent was obtained from the patients before taking part in the trial.