Anti-TNFR2 monoclonal antibody LBL-019 in patients with advanced malignant tumors: A phase I, first-in-human, open-label, multicenter, dose escalation Study.

e14580 Background: LBL-019 is a humanized monoclonal IgG1 antibody against TNF receptor 2 (TNFR2). It specifically binds to TNFR2 with high affinity, co-stimulates TNFR2 in Fc crosslinking-dependent manner, results in activation of NF-κB signaling and T cell activation and expansion, promoting antitumor immunity. Here we report the preliminary safety and efficacy of LBL-019 in patients with advanced malignant tumors. Methods: This is a phase Ⅰ, open-label, multicenter, dose-escalation study to evaluate the safety, tolerability, and PK of LBL-019 in patients with advanced solid tumors that progressed after standard systemic therapy. The dose escalation phase consists of 7 dose cohorts of LBL-019 at 0.2, 0.8, 3, 10, 15, 20, and 30 mg/kg (iv Q2W), using accelerated titration design (first dose) followed by 3+3 design. The primary endpoints were tolerability and safety. The second objectives were pharmacokinetics, pharmacodynamics, and preliminary efficacy (per RECIST 1.1). Results: As of January 02, 2024, 26 patients 17 (65.4%) male, median age 57 years (range:27, 72), 22 (84.6%) ECOG score of 1 were treated in phase Ⅰ. Tumor types include 7 (26.9%) hepatocellular carcinoma (HCC), 4 (15.4%) melanoma, and 15 (57.7%) other tumors. 19 (73%) previously received anti-PD(L)-1 treatment. During the study, no DLT was observed, and the MTD was not reached. The median follow-up was 12.2 months (95%CI: 7.5, 15.9). 19 patients (73.1%) experienced TRAEs of all grades, with 2 (7.7%) having grade ≥3 TRAEs. The most common TRAEs (≥10%) included lipase increased (19.2%), anaemia (19.2%), aspartate aminotransferase increased (15.4%), pruritus (11.5%), rash (11.5%). Treatment interruption and permanent discontinuation due to TEAEs occurred in 12 (46.2%) and 1 (3.8%) patient, respectively. Thirteen patients (50.0%) experienced SAEs, and one of SAE was related to treatment. Out of 23 who underwent efficacy evaluation, 1 patient with HCC achieved PR, and 7 patients achieved SD. The patient with PR and 6 patients with SD received prior immunotherapy, the ORR and DCR were 4.3% and 34.8%, respectively. The DoR in the patient with PR has exceeded 10 months. Conclusions: LBL-019 is well tolerable and has demonstrated preliminary efficacy in patients with advanced malignant tumors. Clinical trial information: NCT05223231 .