产品速递 | 复宏汉霖PD-L1靶向ADC HLX43II期研究完成首例受试者给药

近年来，以抗PD-1/L1抗体为代表的免疫检查点抑制剂（ICI）促进了肿瘤免疫治疗的高速发展，成为肿瘤患者各线治疗的主要手段之一。然而，部分PD-L1阳性患者对该疗法无响应，或者出现耐药^[1]。对于免疫治疗耐药或经免疫治疗等标准治疗失败后的患者人群，尚缺少有效的后线治疗方案，亟待探索更前沿的新型治疗方案，进一步提高患者的临床获益。ADC作为当下肿瘤治疗中疗效最突出的新型疗法，已在乳腺癌、肺癌、食管癌、胃癌等多项实体瘤中展现出初步的治疗潜力，成为重要的探索方向^[2]。而PD-L1在非小细胞肺癌、结直肠癌、三阴性乳腺癌、鳞状细胞癌等多种癌种中均有表达，且在正常组织中的表达有限，使其成为开发ADC药物的潜力靶点，为肿瘤治疗带来新的途径^[3]。

HLX43为复宏汉霖首批进入临床阶段的ADC产品之一，旨在解决PD-1/L1免疫疗法不响应或耐药问题，填补更多晚期/转移性实体瘤患者未满足的临床需求。HLX43兼具抗体分子的高度靶向性和细胞毒素的强大杀伤力，可通过与肿瘤细胞表面PD-L1 抗原特异性结合，经内吞后释放小分子毒素，从而发挥抗肿瘤作用。2023年，HLX43治疗晚期/转移性实体瘤的I期临床试验申请先后获中国国家药品监督管理局（NMPA）和美国食品药品管理局（ FDA）批准，并于2023年11月在中国境内完成首例患者给药。2024年12月，HLX43单药或联合治疗晚期/转移性实体瘤的Ib/II期临床试验申请获NMPA批准。临床前研究及I期临床研究提示，HLX43在PD-1/PD-L1单抗耐药的非小细胞肺癌、宫颈癌、食管鳞癌、肝癌等多个瘤种中显示出显著疗效，且耐受性良好，临床前研究数据于2023欧洲肿瘤内科学会（ESMO）大会以壁报形式进行展示。基于此，复宏汉霖计划于近期启动HLX43在包括食管鳞癌、宫颈癌、肝细胞癌、鼻咽癌、头颈部鳞癌、非小细胞肺癌等实体瘤中的II期临床试验，以进一步评HLX43的疗效和安全性。

未来，复宏汉霖将持续立足于未满足的临床需求，充分发挥公司在抗体药物和抗体偶联药物领域的一体化平台优势，加速推动更多前沿治疗方案的研究和开发，为全球患者带来更多高质量、可负担的创新治疗方案。

First Subject Dosed for a Phase 2 Clinical Trial of Henlius’ PD-L1-Targeting ADC HLX43

Recently, Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first subject has been dosed for a phase 2 clinical trial of HLX43 for Injection (HLX43-ESCC201), the novel Programmed Death-Ligand 1 (PD-L1)-targeting antibody-drug conjugate (ADC) that developed by the company based on the collaboration with MediLink Therapeutics, for the treatment of patients with recurrent/metastatic esophageal squamous cell carcinoma (ESCC).  At present, no PD-L1 targeting ADC has been approved for marketing globally, and only SGN-PDL1V from Pfizer is about to innitiate a Phase 3 clinical trial. HLX43 is the second PD-L1-targeting ADC to enter clinical trial globally.

Immune checkpoint inhibitors represented by PD-1/PD-L1 monoclonal antibodies have emerged in recent years and revolutionised all lines of treatment for tumour patients. However, there are still many patients with positive PD-L1 expression who do not respond to or develop resistance to PD-1/PD-L1-targeted therapy^[1]. To date, there has been no subsequent-line treatment for patients who are resistant to PD-1/L1 immunotherapy or failed to benefit from the standard treatments including immunotherapy, indicating a significant unmet medical need to further improve the clinical benefits for these patients. As a novel targeting therapy with the most prominent anti-tumour efficacy, ADCs have shown preliminary therapeutic potential in the treatment of multiple advanced solid tumours, such as breast cancer(BC), lung cancer(LC), esophageal cancer(EC) and gastric cancer(GC) ,making it a promising therapeutic in solid tumours^[2]. PD-L1 is expressed in patients across a broad spectrum of tumour types including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), triple negative breast cancer (TNBC), squamous cell carcinoma and displays limited expression on normal tissues, highlighting the potential of PD-L1 as a target for ADCs, which may bring new options for cancer treatment^[3].

HLX43 is one of the first ADC candidates of Henlius to enter into clinical development. Combining the selectivity of targeted monoclonal antibodies with the highly potent cytotoxic agent, HLX43 could exert anti-tumour effects through specific binding to the PD-L1 expressed on the surface of tumour cells and release cytotoxic payloads after internalisation by the cancer cells. In 2023, the application for phase 1 clinical trial of HLX43 for the treatment of advanced/metastatic solid tumours was approved by the China National Medical Products Administration (NMPA) and the U.S. Food and Drug Administration (FDA), respectively. And the first patient has been dosed in this trial in November 2023 in the Chinese Mainland. In December 2024, the application for a phase 1b/2 clinical trial of HLX43 for the monotherapy or combination therapy of advanced/metastatic solid tumours has been approved by the NMPA. Several non-clinical studies and the phase 1 clinical trial have shown that, HLX43 has good anti-tumour effects and a favorable tolerability profile in non-small cell lung cancer (NSCLC) , cervical cancer (CC), ESCC, hepatocellular carcinoma (HCC), and other tumour types that were PD-1/L1 mAb-resistant. The results of the pre-clinical studies  were published as poster presentation at the 2023 European Society of Medical Oncology (ESMO) Congress. Based on this, Henlius plans to initiate phase 2 clinical trials of HLX43 for potential solid tumour indications including ESCC, CC, HCC, nasopharyngeal carcinoma(NPC), head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC)，to further evaluate the efficacy and safety of HLX43 in patients.

With a particular focus on addressing the unmet medical needs, Henlius will further take efforts to accelerate the R&D of more cutting-edge therapeutic options and promote the layout of our innovative portfolio based on the company’s competitive edge of an integrated antibody drug R&D platform, bringing more high-quality and affordable therapeutics for patients worldwide.

媒体：PR@Henlius.com

投资者：IR@Henlius.com