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EGFR×HER3双特异性抗体偶联药物
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创国产新药出海预付款纪录,百利天恒双抗ADC临床试验结果登上Nature Medicine
生物世界· 2025-07-11 03:41
Core Viewpoint - Esophageal squamous cell carcinoma (ESCC) is a significant cause of cancer-related mortality, with current treatments showing limited long-term survival rates, necessitating the development of new therapeutic strategies [2][3]. Group 1: Current Treatment Landscape - Immune checkpoint inhibitors combined with platinum-based chemotherapy are standard treatments for advanced ESCC, but only 10%-20% of patients achieve long-term survival due to drug resistance [2]. - Second-line treatment with Irinotecan has limited efficacy, with an objective response rate (ORR) not exceeding 10% [2]. Group 2: New Treatment Development - A bispecific antibody-drug conjugate (ADC) targeting EGFR and HER3, named BL-B01D1, has been developed by Sichuan BaiLi TianHeng Pharmaceutical Co., Ltd., marking the first clinical trial of this type of drug globally [7]. - The drug is designed to connect a bispecific antibody with a topoisomerase I inhibitor via a cleavable linker [7]. Group 3: Clinical Trial Results - The phase 1b trial of BL-B01D1 involved 82 previously treated ESCC patients, showing an overall confirmed objective response rate (cORR) of 29.3% and a disease control rate of 79.2% at a dose of 2.5 mg/kg [10]. - The trial established a recommended dose for phase 2 trials at 2.5 mg/kg, administered every three weeks, with a 63.3% incidence of grade 3 treatment-related adverse events [12]. Group 4: Collaboration and Future Directions - The collaboration with Bristol-Myers Squibb (BMS) is notable, with a total deal value of up to $8.4 billion, including an $800 million upfront payment, setting a record for domestic innovative drugs [9]. - The research team has initiated phase 3 clinical trials based on the promising results of BL-B01D1 [13].