LBL-024 Advanced Drug Monograph

LBL-024 Medication Report

Name: LBL-024 Name (English): LBL-024

Drug Type: Bispecific antibody

Target: PD-L1 and 4-1BB

Mechanism of Action: LBL-024 is a bispecific antibody that simultaneously targets Programmed Death Ligand-1 (PD-L1) and the co-stimulatory receptor 4-1BB (CD137). It blocks the PD-1/PD-L1 immunosuppressive pathway and selectively co-stimulates 4-1BB in the tumor microenvironment, enhancing T-cell activation and anti-tumor immune responses. Upon 4-1BB binding, LBL-024 acts as a conditional 4-1BB agonist in the tumor microenvironment (TME), resulting in T-cell co-stimulation and enhanced T-lymphocyte-mediated anti-tumor activity.

Therapeutic Areas: Neoplasms, Respiratory Diseases

Active Indication: Advanced Malignant Tumors, Neuroendocrine Carcinoma (EP-NEC), Non-Small Cell Lung Cancer (NSCLC), Small Cell Lung Cancer (SCLC), Biliary Tract Cancer (BTC), Ovarian Cancer (OC), Esophageal Squamous Cell Carcinoma (ESCC).

R&D Status:

• Phase 2: Non-Small Cell Lung Cancer (China), Advanced Lung Non-Small Cell Carcinoma (China), Advanced Malignant Solid Neoplasm (China), Advanced Neuroendocrine Carcinoma (China), Advanced cancer (China).
• Pivotal Study (Phase IIb): Extrapulmonary Neuroendocrine Carcinomas (China).

Clinical Trial Information:

• NCT05170958: A Phase I/II Clinical Study of LBL-024 in Patients With Advanced Malignant Tumors.

Efficacy Data:

• In a Phase I/II study, LBL-024 demonstrated promising efficacy and a favorable safety profile in patients with advanced EP-NEC.
• At a dose of 15 mg/kg, the Objective Response Rate (ORR) was 37.5% and the Disease Control Rate (DCR) was 50.0% in second-line EP-NEC.
• An ORR of 54.5% was observed in patients with PD-L1 negative expression (CPS<1).
• In a Phase Ib/II trial combining LBL-024 with etoposide/platinum-based chemotherapy in treatment-naive advanced EP-NEC, encouraging efficacy was observed.

Safety Profile:

• LBL-024 has shown a good safety profile in clinical trials.
• The majority of Treatment-Related Adverse Events (TRAEs) were grade 1-2.
• Common TRAEs (≥15%) included anemia, increased AST, increased ALT, and decreased white blood cell count.
• No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached in the Phase I study.

Regulatory Designations:

• Breakthrough Therapy Designation (BTD): Granted by the National Medical Products Administration (NMPA) in China for the treatment of extrapulmonary neuroendocrine carcinoma (October 2024).
• Orphan Drug Designation (ODD): Granted by the U.S. Food and Drug Administration (FDA) for the treatment of neuroendocrine cancer (November 2024).

Potential: LBL-024 has the potential to be a first-in-class treatment for extrapulmonary neuroendocrine carcinoma and other advanced malignancies, especially for patients who have failed prior lines of therapy. Its unique bispecific design aims to enhance anti-tumor immunity while maintaining a favorable safety profile.