LEADS BIOLABS-B (09887) announced that the first patient has been successfully dosed in an open-label, multicenter Phase Ib/II clinical study evaluating Velesin™ (Opatisumimab, LBL-024), a PD-L1/4-1BB bispecific antibody, for the treatment of recurrent or metastatic triple-negative breast cancer. The trial is led by Professor Yin Yongmei from Jiangsu Provincial People's Hospital and is being conducted simultaneously across multiple hospitals in China. The study aims to assess the efficacy and safety of Opatisumimab, both as a monotherapy and in combination with nab-paclitaxel, for patients with recurrent or metastatic triple-negative breast cancer.
Velesin™ is a bispecific antibody that simultaneously targets PD-L1 and 4-1BB. It is the world's first therapy targeting the 4-1BB receptor to reach the registration clinical stage for extra-pulmonary neuroendocrine carcinoma. In Phase II or registration clinical trials for three indications—non-small cell lung cancer, small-cell lung cancer, and extra-pulmonary neuroendocrine carcinoma—Velesin™ has demonstrated potential for best-in-class or first-in-class clinical activity. It also has the potential to become the first approved treatment for advanced extra-pulmonary neuroendocrine carcinoma.
Utilizing the company's proprietary X-body® platform, Velesin™ is designed with an optimal 2:2 structure. This design alleviates PD-1/L1-mediated immunosuppression while enhancing 4-1BB-regulated T-cell activation, resulting in a synergistic tumor-killing effect. It possesses broader potential for treating various cancers compared to PD-1/L1 inhibitors alone. In two clinical trials in China, Velesin™ has shown encouraging efficacy signals and a favorable safety profile in patients with advanced extra-pulmonary neuroendocrine carcinoma, both as a monotherapy and in combination with chemotherapy.
The company received approval from the National Medical Products Administration (NMPA) in April 2024 to initiate a single-arm registration clinical trial. In October 2024, it obtained Breakthrough Therapy Designation (BTD) from the NMPA for LBL-024 in treating advanced extra-pulmonary neuroendocrine carcinoma after prior therapies. In November 2024, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for the treatment of neuroendocrine carcinoma. In January 2026, the FDA granted Fast Track Designation for the treatment of extra-pulmonary neuroendocrine carcinoma, and in the same month, the European Commission granted Orphan Drug Designation for this indication.
The 4-1BB agonist function can reactivate exhausted T-cells and promote their proliferation, making it particularly suitable for treating "cold tumors" that are resistant or unresponsive to PD-1/PD-L1 inhibitors. Beyond extra-pulmonary neuroendocrine carcinoma, Velesin™ has shown encouraging clinical signals in multiple cancer types with significant unmet medical needs, including small-cell lung cancer, biliary tract cancer, ovarian cancer, non-small cell lung cancer, esophageal squamous cell carcinoma, hepatocellular carcinoma, gastric cancer, triple-negative breast cancer, and melanoma. Encouraging clinical outcomes have already been observed in cancers such as non-small cell lung cancer, small-cell lung cancer, biliary tract cancer, and ovarian cancer.
Cancer remains a leading cause of global morbidity and mortality. Globally, breast cancer is the second most commonly diagnosed cancer after lung cancer, with approximately 2.3 million new cases annually, and the fourth leading cause of cancer-related deaths, with about 670,000 fatalities per year. In China, the number of new breast cancer cases continues to rise, estimated at 360,000 annually, with approximately 75,000 deaths. Triple-negative breast cancer (TNBC), a subtype characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, accounts for about 15% to 20% of all breast cancer cases. It is known for its high malignancy, elevated recurrence rate, poor prognosis, and short overall survival.
Compared to other breast cancer subtypes, TNBC is considered "immune-enriched" or a "hot tumor." While immunotherapy combined with chemotherapy has extended progression-free survival (PFS) in PD-L1 positive populations, the median PFS still has room for improvement, highlighting the need for more effective treatment options. For PD-L1 negative populations, clinical guidelines in China and internationally still recommend chemotherapy as the standard of care, indicating a significant unmet clinical need within this patient group.