Nanjing Leads Biolabs Co., Ltd. announced that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation to LBL-024 for the treatment of patients with advanced extrapulmonary neuroendocrine carcinoma (EP-NEC) who have progressed after receiving two or more lines of chemotherapy. LBL-024 is a bispecific antibody independently developed by Leads Biolabs with global intellectual property rights, targeting both PD-L1 and 4-1BB.
The Breakthrough Therapy Designation was awarded based on the remarkable clinical efficacy and safety profile of LBL-024 in patients with advanced EP-NEC who had failed second-line and above chemotherapy. Current clinical data demonstrates that LBL-024 monotherapy has more than doubled both the Objective Response Rate (ORR) and Overall Survival (OS) compared to existing treatments for this disease.
Clinical Efficacy
Findings from a phase 1/2 trial presented at the 2024 ASCO Annual Meeting showed promising results. Among patients with EP-NEC who underwent at least one tumor assessment (n = 45), the overall response rate (ORR) was 33.3%, with all responders achieving a partial response (PR). The disease control rate (DCR) was 51.1%. In the overall population (n = 47), the PR, stable disease, and progressive disease rates were 31.9%, 17.0%, and 46.8%, respectively; 4.3% of patients were not evaluable.
At the recommended phase 2 dose (RP2D) of 15 mg/kg, LBL-024 elicited an ORR of 33.3% and a DCR of 48.5%.
Additional data showed that for patients with EP-NEC treated across the study, the median DOR was 5.3 months. For those treated in the second line and in the third line or later, the median DOR was 4 months and 7 months, respectively. The overall median PFS was 2.8 months; the median PFS for those treated in the second line and those treated in the third line or later was 4.1 months and 2.7 months, respectively.
The median overall survival (OS) was not reached at a median follow-up of 8.5 months. The respective 6-month OS rates for the overall population, the second-line population, and the third-or-later-line population were 61.7%, 72.7%, and 52.0%.
Safety Profile
Regarding safety for all treated patients (n = 175), the rates of any-grade treatment-emergent adverse effects (TEAEs), treatment-related AEs (TRAEs), serious AEs, and serious TRAEs were 92.0%, 77.1%, 33.1%, and 16.6%, respectively. Grade 3 or higher AEs occurred in 39.4% of patients, and the rate of grade 3 or higher TRAEs was 20.6%. TRAEs led to dose interruptions and treatment discontinuation in 22.3% and 4.0% of patients, respectively. No dose-limiting toxicities were reported, and the maximum tolerated dose was not reached in phase 1.
The most common TEAEs included anemia (any-grade, 33.1%; grade ≥ 3, 5.1%), increased aspartate aminotransferase (32.6%; 1.1%), and increased alanine aminotransferase (27.4%; 0.6%).
LBL-024 Mechanism of Action
LBL-024 is a tetravalent bispecific antibody that simultaneously targets PD-L1 and 4-1BB, serving dual functions: blocking the immunosuppressive PD-1/PD-L1 pathway, and selectively co-stimulating 4-1BB in the tumor microenvironment to enhance immune responses. The dual functions of LBL-024—lifting PD-1/PD-L1 immune inhibition and intensifying 4-1BB modulated T cell activation—synergistically enhance the anti-tumor immune response.
The Need for New Therapies in EP-NEC
Neuroendocrine carcinoma (NEC) is a class of poorly differentiated, high-grade neuroendocrine neoplasms (NENs). EP-NEC exhibits similar aggressive and metastatic characteristics to small cell lung cancer (SCLC). Most patients are diagnosed at a later stage or already have distant metastases, resulting in rapid disease progression and a poor prognosis.
Currently, the primary first-line treatment for advanced EP-NEC involves platinum-based chemotherapy, achieving an overall response rate (ORR) of approximately 30% to 50%, with a median overall survival (mOS) of only approximately one year. Treatment options for advanced EP-NEC are limited, and there are no standard treatment strategies for patients who progress beyond second-line chemotherapy. These underscore the urgency to develop novel therapeutic approaches.
Expert Commentary
Dr. Charles Cai, Chief Medical Officer of Leads Biolabs, stated, “The designation for LBL-024 is another proof of the robust R&D capabilities of Leads Biolabs, and it is also a major victory for Leads Biolabs’ insistence on focusing on the first-in-class product R&D strategy for the global market. Leads Biolabs will vigorously pursue the global clinical development of LBL-024, with the anticipation of offering more effective treatment options for patients with EP-NEC at the earliest opportunity.”
Dr. Xiaoqiang Kang, founder, chairman and CEO of Leads Biolabs, added, “Leads Biolabs has consistently embraced differentiated innovation, and we eagerly anticipate the timely market introduction of LBL-024 as a novel immunotherapy, following the groundbreaking successes of anti-PD-1/PD-L1, CTLA-4, and LAG-3.”
