产品速递 | 复宏汉霖PD-L1 ADC HLX43 Ib/II期临床试验申请获NMPA批准

近年来，以抗PD-1/L1抗体为代表的免疫检查点抑制剂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]。鉴于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^[2]。尤其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ADC或ADC联合其他抗癌药物的联用治疗方案，进一步提高患者的临床获益。

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。目前，HLX43已在临床前药理学研究、药代动力学研究及安全性评价中展现出抗肿瘤活性，且具有良好的安全性。该研究数据于2023欧洲肿瘤内科学会（ESMO）大会以壁报形式进行展示。正在开展的一项评估HLX43在晚期/转移性实体瘤患者中的安全性、耐受性及药代动力学特征的I期临床研究（NCT06115642）也显示，HLX43 给药剂量已递增至4.0mg/kg，每三周静脉滴注一次（Q3W），患者耐受性良好，且既往接受了包括免疫治疗在内的标准治疗后进展的实体瘤患者（非小细胞肺癌、宫颈癌等）仍表现出对HLX43 的治疗响应。因此，复宏汉霖计划进一步在多种实体瘤中开展Ib/II 期研究，探索标准治疗后使用HLX43 单药或联合治疗的疗效及安全性，在更广泛的人群中验证HLX43 的疗效和安全性。

未来，复宏汉霖还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，不断拓展疾病领域和新分子类型，为全球患者带来更多高质量、可负担的创新治疗方案。

Henlius Receives IND Approval from NMPA for a Phase 1b/2 Clinical Trial of Its Novel PD-L1-Targeting ADC HLX43

Shanghai, China, December 4, 2024 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the investigational new drug (IND) application for a phase 1b/2 clinical trial of HLX43 for Injection, the antibody-drug conjugate (ADC) product that developed by the company based on the collaboration with MediLink Therapeutics, has been approved by the China National Medical Products Administration (NMPA), for monotherapy or combination therapy to treat patients with  advance/metastatic solid tumours. In November 2023, a phase 1 clinical trial of HLX43 has completed dosing its first subject, making it the first PD-L1-targeting ADC in China to enter a clinical trial. At present, no PD-L1 targeting ADC has been approved for marketing 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]. 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^[2]. 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 for this patient population. ADCs and ADCs combining immunotherapies are promising therapeutic strategies to further improve the clinical benefits for patients.

HLX43 is one of the first ADC candidates of Henlius to enter into clinical development. It is designed to address the issues of unresponsiveness or resistance to PD-1/L1 immunotherapies to fulfill the unmet medical needs of advanced/metastatic patients. 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. Up to date, HLX43 has exhibited good anti-tumour effects and a favorable safety profile in nonclinical pharmacology, pharmacokinetic studies and safety evaluation. The results of the studies were published as poster presentation at the 2023 European Society of Medical Oncology (ESMO) Congress. Meanwhile, in a phase 1 clinical trial aims to evaluate the safety, tolerability and pharmacokinetics of HLX43 in patients with advanced/metastatic solid tumours, when the administration dose of HLX43 has been escalated to 4.0 mg/kg, every 3 weeks by intravenous infusion, it was well tolerated by patients. And patients with solid tumours (including non-small cell lung cancer, cervical cancer, etc.) who have progressed after prior standard treatment also respond to HLX43 treatment. Therefore, the company plans to initiate a phase 1b/2 clinical trial to explore the efficacy and safety of HLX43 monotherapy or HLX43 combination therapy in a variety of solid tumours patients who failed standard treatment, further validating the efficacy and safety of the product in broader patient population.

With a particular focus on addressing the unmet medical needs, Henlius will further take efforts to 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.