产品速递 | 探索更广泛瘤种治疗潜力，复宏汉霖创新型抗HER2单抗HLX22 II期临床试验申请获NMPA批准

表皮生长因子受体（EGFR）家族包括EGFR（HER1）、表皮生长因子受体2（HER2）、HER3及HER4，在肿瘤发生、转移及化疗耐药性等信号传导中发挥重要作用^[3]。其中，HER2的基因突变、扩增和蛋白过表达已被证实广泛存在于乳腺癌、胃癌、胆道癌、胰腺癌、尿路上皮癌、肺癌等多项实体瘤中，成为肿瘤治疗中的经典靶点^[4]。抗HER2靶向药物的出现，很大程度上改善了HER2阳性乳腺癌及胃癌等患者群体的生存获益^[5,6]。且随着新型抗HER2药物如HER2双靶疗法、抗体-药物偶联物（ADCs）等的发展，抗HER2靶向治疗正逐步从乳腺癌及胃癌扩展到多种其他实体瘤，为这些患者提供了新的治疗选择^[7]。

HLX22为复宏汉霖自AbClon, Inc.许可引进、并后续自主研发的靶向HER2的创新型单克隆抗体。HLX22可结合在HER2的胞外亚结构域IV，但结合表位与曲妥珠单抗有所不同，使得HLX22和曲妥珠单抗能够同时与HER2结合，促进HER2二聚体（HER2同源二聚体及HER2/EGFR异源二聚体）的内吞和降解，从而产生更强的受体阻断效果。临床前研究表明，HLX22与曲妥珠单抗联合治疗能够协同抑制肿瘤细胞增殖和诱导细胞凋亡，在体内和体外均表现出增强的抗肿瘤活性。同时，HLX22的I期临床试验验证了产品安全性[8]，HLX22联合曲妥珠单抗及化疗一线治疗HER2阳性胃/胃食管交界部（G/GEJ）癌的II期临床研究结果也显示，在曲妥珠单抗联用化疗的基础上加入HLX22可明显改善HER2阳性G/GEJ癌患者一线治疗的效果，且安全性可控^[1,2]。目前，HLX22联合曲妥珠单抗和化疗一线治疗HER2阳性晚期G/GEJ的国际多中心III期临床试验相继获中国、美国、日本、澳大利亚临床试验许可，并于中国完成首例患者给药。

未来，复宏汉霖将持续加码创新，以临床需求为先导，持续探索新型抗HER2靶向疗法在肿瘤中的治疗潜力，高效推进HLX22的全球临床开发进展，为全球患者提供更多可负担、疗效更好的治疗方案。

Henlius Receives Approval form NMPA for a Phase 2 Clinical Trial of Its Novel Anti-HER2 mAb HLX22 

Shanghai, China, December 4, 2024 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the investigational new drug (IND) application for a phase 2 clinical trial of the company’s novel anti-HER2 monoclonal antibody (mAb), HLX22, in combination with trastuzumab and chemotherapy or combined with trastuzumab deruxtecan (T-DXd) has been approved by the China National Medical Products Administration (NMPA), for the treatment of HER2-expressing solid tumours. As a novel HER2-targeting mAb, HLX22 has a synergistic anti-tumor effect in combination with trastuzumab. The dual-HER2 blockade therapy has demonstrated anti-tumor efficacy and good safety in investigational studies for the first-line treatment of advanced gastric cancer^[1,2]. Therefore, Henlius intends to further explore the efficacy and safety of HLX22-based anti-HER2 therapies in various types of solid tumours, expected to bring clinical benefits to a wider group of patients with solid tumours. 

Epidermal growth factor receptor (EGFR) family signaling contributes to neoplastic cell growth, malignant transformation, and resistance to chemotherapy. Human epidermal growth factor receptor 2 (HER2) belongs to human EGFR family, including EGFR (HER1), HER3, and HER4^[3]. From which, the HER2 alterations, including HER2 mutation, HER2 amplification and HER2 overexpression have been found in a broad spectrum of tumour types, such as breast cancer, gastric cancer, biliary tract cancer, pancreatic cancer, uroepithelial cancer, and lung cancer, making it a well-established therapeutic target in tumours treatment^[4]. The research and development of anti-HER2 therapeutics has significantly improved the survival of HER2- positive breast cancer and gastric cancer patients^[5,6]. Moreover, with advances in HER2-targeting agents like dual anit-HER2 therapy and antibody drug conjugates (ADCs), HER2-targeted therapeutics have expanded to other tumour types beyond breast cancer and gastric cancer, providing new treatment options for these patients^[7].

HLX22 is an innovative anti-HER2 mAb introduced from AbClon, Inc. and further investigated and developed by Henlius. HLX22 can bind to HER2 extracellular subdomain IV at a binding site different from that of trastuzumab, which allows simultaneous binding of HLX22 and trastuzumab to HER2 dimers (HER2 homodimer and HER2/EGFR heterodimer) on tumour cell surface, thereby promoting the internalization and HER2 dimer degradation. Pre-clinical studies showed that the co-treatment with HLX22 and trastuzumab synergistically inhibited tumour cell proliferation and apoptosis, which led to enhanced anti-tumour activity in vitro and in vivo. A phase 1 clinical trial of HLX22 demonstrates that HLX22 was well tolerated and had a favorable safety profile^[8].And HLX22-GC-201，the phase 2 clinical trial of HLX22 combined with trastuzumab showed that adding HLX22 to HLX02 (trastuzumab for injection) + XELOX improved survival and anti-tumour response in patients with HER2-positive gastric/gastroesophageal junction (G/GEJ) cancer in the first-line setting, with a manageable safety profile^[1,2] . Up to date, the phase 3 international multicenter clinical study of HLX22 in combination of trastuzumab and chemotherapy for the treatment of HER2 positive advanced G/GEJ cancer has received regulatory approvals in China, the U.S., Japan and Australia, respectively. And the first subject has been dosed for this MRCT in China.

Looking forward, Henlius will actively improve efficiency through innovations, with a particular focus on addressing the unmet medical needs. This includes continuing to explore the therapeutic potential of novel HER2 dual-target therapies in oncology, efficiently promoting the global clinical development of HLX22, so as to provide more high-quality and affordable therapies for patients worldwide.