Nanjing Leads Biolabs announced groundbreaking clinical results for LBL-024, an anti-PD-L1/4-1BB bispecific antibody, in treating advanced extrapulmonary neuroendocrine carcinoma (EP-NEC). The multicenter phase Ib/II trial data, presented at the 2025 ASCO Annual Meeting, demonstrated a 75% overall response rate when LBL-024 was combined with etoposide plus platinum-based chemotherapy in treatment-naive patients.
Strong Efficacy Signals Across Dose Levels
In 52 efficacy-evaluable patients, the combination therapy achieved an overall response rate (ORR) of 75.0% and disease control rate (DCR) of 92.3% across all dose levels. These results significantly exceeded historical ORR data of 30-55% with chemotherapy alone in this patient population.
The 15 mg/kg dose demonstrated the strongest anti-tumor activity, achieving an ORR of 83.3% and a DCR of 100%. Notably, 57.7% of patients (30/52) experienced greater than 50% tumor shrinkage. As of April 15, 2025, with a median follow-up of 8.2 months, progression-free survival data remains immature but shows promising durability trends across all dose groups.
Favorable Safety Profile
The phase Ib dose escalation stage revealed no dose-limiting toxicities. Most treatment-emergent adverse events were Grade 1-2 and manageable, primarily associated with chemotherapy components including hematologic toxicity and nausea. No unexpected safety signals were identified during the study.
Regulatory Recognition and Development Strategy
LBL-024 has garnered significant regulatory attention, receiving Breakthrough Therapy Designation from China's National Medical Products Administration in October 2024 and Orphan Drug Designation from the U.S. FDA for neuroendocrine carcinoma in November 2024. The drug received regulatory clearance in April 2024 to initiate a single-arm pivotal trial in China, marking it as the first 4-1BB targeted agent globally to reach this developmental stage.
"We are thrilled to share these exciting clinical data, which strongly support the advancement of LBL-024 into a pivotal phase III trial as a first-line treatment for EP-NEC," stated Dr. Charles Cai, Chief Medical Officer of Leads Biolabs. "Our strategy prioritizes efficient development through single-arm registrational trial in underserved indications, while also maximizing value through broad indication expansion."
Novel Mechanism and Broader Applications
LBL-024 represents a potential first-in-class bispecific antibody simultaneously targeting PD-L1 and the co-stimulatory receptor 4-1BB. Developed using Leads Biolabs' proprietary X-Body™ bispecific platform, the drug features a 2:2 format with two binding domains each for PD-L1 and 4-1BB, along with an optimized affinity ratio. This design enables LBL-024 to reverse PD-L1-mediated immune suppression while selectively enhancing T cell activation.
Beyond neuroendocrine carcinoma, LBL-024 has shown encouraging early activity in other tumor types, including small cell lung cancer, ovarian cancer, and biliary tract cancer. The company is exploring expansion into broader indications such as non-small cell lung cancer, esophageal squamous cell carcinoma, hepatocellular carcinoma, and gastric cancer.
Addressing Unmet Medical Need
Extrapulmonary neuroendocrine carcinoma represents a malignancy with significant unmet medical need, lacking a standard of care. This clinical gap supports the pursuit of accelerated approval through a single-arm pivotal study design. LBL-024 holds promise to become the first approved treatment specifically developed for EP-NEC.
The study was led by Professor Shen Lin of Peking University Cancer Hospital and conducted across multiple clinical centers. The trial (NCT06157827) was among 32 Chinese-led studies selected for oral presentation at ASCO 2025, which received a record-breaking 7,775 abstract submissions.
