LEADS BIOLABS-B(09887): The first patient in the phase IB/II trial of Verlisin for recurrent or metastatic triple-negative breast cancer.

LEADS BIOLABS-B(09887) announced that the first patient in the phase Ib/II clinical study of LBL-024, a dual-specificity antibody targeting PD-L1/4-1BB (also known as Optaratumab monoclonal antibody), for the treatment of recurrent or metastatic triple-negative breast cancer, has successfully received treatment. The open-label, multicenter phase Ib/II clinical study is led by Professor Yin Yongmei from Jiangsu Provincial People's Hospital and is being conducted simultaneously in multiple hospitals nationwide. The trial aims to evaluate the efficacy and safety of Optaratumab monoclonal antibody alone or in combination with albumin-bound paclitaxel in patients with recurrent or metastatic triple-negative breast cancer. Optaratumab monoclonal antibody, marketed as Vilixen, is a dual-specificity antibody targeting PD-L1 and 4-1BB, making it the first therapy globally to target the 4-1BB receptor in extra-pulmonary neuroendocrine tumors to reach the registration clinical stage. In phase II or registration clinical trials for non-small cell lung cancer, small cell lung cancer, and extra-pulmonary neuroendocrine tumors, Vilixen has demonstrated superior clinical activity compared to similar agents. Vilixen also has the potential to become the first approved therapy for advanced extra-pulmonary neuroendocrine tumors. Utilizing the proprietary X-body platform with intellectual property rights, Vilixen was designed with an optimal 2:2 structure to alleviate PD-1/L1 immune suppression and enhance 4-1BB-mediated T cell activation, achieving a synergistic effect in tumor eradication and possessing a broader potential for cancer treatment compared to PD-1/L1 inhibitors. In two clinical trials in China, Vilixen has shown promising efficacy and good safety as a monotherapy or in combination with chemotherapy for advanced extra-pulmonary neuroendocrine tumors. The company was approved by the National Medical Products Administration (NMPA) in April 2024 to conduct a single-arm registration clinical trial, received Breakthrough Therapy Designation (BTD) for LBL-024 in the treatment of advanced extra-pulmonary neuroendocrine tumors from the NMPA in October 2024, Orphan Drug Designation for the treatment of neuroendocrine tumors from the FDA in November 2024, Fast Track designation for the treatment of extra-pulmonary neuroendocrine tumors from the FDA in January 2026, and Orphan Drug Designation for the treatment of extra-pulmonary neuroendocrine tumors from the European Commission in January 2026. As an agonist, 4-1BB can reactivate apoptotic T cells and expand them greatly, making it particularly suitable for treating "cold tumors" resistant or unresponsive to PD-1/PD-L1. In addition to extra-pulmonary neuroendocrine tumors, Vilixen has shown promising clinical signals in various cancers with unmet medical needs, such as small cell lung cancer, cholangiocarcinoma, ovarian cancer, non-small cell lung cancer, esophageal squamous cell carcinoma, hepatocellular carcinoma, gastric cancer, triple-negative breast cancer, and melanoma, with exciting clinical outcomes observed in multiple cancers including non-small cell lung cancer, small cell lung cancer, cholangiocarcinoma, and ovarian cancer. Cancer is one of the leading causes of morbidity and mortality globally. Breast cancer ranks second in global incidence, following only lung cancer, with approximately 2.3 million new cases each year, and is the fourth leading cause of cancer-related deaths, accounting for around 670,000 deaths annually. In China, the number of new cases of breast cancer continues to rise, estimated at 360,000 per year, with approximately 75,000 deaths. Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, accounting for approximately 15-20% of all breast cancers and known for its high malignancy, high recurrence rate, poor prognosis, and short overall survival. Compared to other breast cancer subtypes, TNBC is considered to be "immune-enriched" or a "hot tumor." Immune combination therapy has extended the progression-free survival (PFS) of PD-L1 positive patients, but there is still room for improvement in the median PFS, highlighting the need for more effective treatment options; for PD-L1 negative patients, chemotherapy is still recommended as the standard treatment in both domestic and international clinical guidelines, indicating unmet clinical needs in this population.