A novel and uniquely designed bispecific antibody (LBL-024) against PD-L1 and 4-1BB in patients with advanced malignant tumors and neuroendocrine carcinoma: A report of safety and robust efficacy of LBL-024 monotherapy in phase I/II, first-in-human, open-label, multicenter, dose escalation/expansion study.

4010 Background: LBL-024 blocks the immunosuppressive pathway of tumor cells by targeting PD-L1 and effectively localizes 4-1BB co-stimulation to the tumor microenvironment, to improve the anti-tumor immune response. Here we report the safety and efficacy of LBL-024 in patients with advanced malignant tumors, particularly the robust clinical benefit in extrapulmonary neuroendocrine carcinoma (EP-NEC). Methods: Patient population: Phase Ⅰ, advanced malignant tumors exhausted standard cares and phase Ⅱ, EP-NEC failed at least one line of chemotherapy. Seven dose levels of LBL-024 were evaluated (0.2, 0.8, 3.2, 6, 10, 15 and 25 mg/kg, i.v. Q3W) and 15 mg/kg was selected for phase Ⅱ. The primary endpoints were tolerability, safety and efficacy (RECIST 1.1) and the second objectives were pharmacokinetics, pharmacodynamics, and other efficacy parameters. Results: By October 31, 2023, 162 patients were enrolled (64 in phase Ⅰ, and 98 in phase Ⅱ). Tumor types include EP-NEC (46, 28.4%), NSCLC (33, 20.4%), biliary tract cancer (31, 19.1%), and other tumors (52, 32.1%). During the dose escalation stage, no DLT was observed, and the MTD was not reached. The median follow-up was 4.2 months (95%CI: 3.9, 4.9). 126 out of 162 patients (77.8%) experienced TRAEs of all grades, with 34 (21.0%) having grade ≥3 TRAEs. The most common TRAEs (≥15%) included anemia (31.5%), AST increased (30.9%), ALT increased (25.3%), and white blood cell count decreased (22.2%). Out of 146 who underwent efficacy evaluation, the ORR and DCR were 15.1% and 46.6%, respectively. Robust efficacy signals were observed in 41 patients with EP-NEC (Table 1). 6 months of DoR will be available for report in ASCO. Conclusions: LBL-024 has showed good safety profile and very promising antitumor effects in patients with advanced malignant tumors, particularly EP-NEC patients who failed at least one line of chemotherapy. The efficacy observed in EP-NEC is significantly higher than the historic reports with immunotherapy (≤10%) and chemotherapy (about 18%). The extremely robust efficacy and good safety profile support a pivotal study for accelerated development of EP-NEC, the highly unmet medical needs and deadly disease. Clinical trial information: NCT05170958 . Table: see text