Matuzumab

近日，复宏汉霖HLX07（创新型抗EGFR单抗）单药或联合疗法在局部晚期、不可切除或转移性食管鳞状细胞癌（ESCC）患者中的II期研究（HLX07-ESCC201) 发表于期刊Cancer Communications (最新影响因子：20.1)。该研究由国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院黄镜教授牵头开展。 食管癌是全球范围内十分常见的恶性肿瘤，主要分型为鳞状细胞癌和腺癌，84%以上属于食管鳞状细胞癌[1]。我国是食管癌高发地区，根据2016年中国恶性肿瘤发病率及死亡率估计，我国食管癌新发病例25.3万，死亡病例19.4万，发病率及死亡率分别位列恶性肿瘤的第6位和第5位[2]。由于早期食管癌症状往往不明显，大多数患者确诊时已处于临床中晚期，失去了手术治疗机会。目前临床对晚期患者主要采用系统治疗（化疗或靶向治疗），但治疗效果有限，复发率和转移率偏高。近年来，肿瘤免疫治疗已经成为国内外研究热点之一，多项研究表明抗PD-1单抗联合化疗可为食管癌患者带来生存获益，包括H药（斯鲁利单抗）在内的免疫检查点抑制剂联合化疗已成为我国食管癌的一线治疗标准[3]，但仍需要寻找更多元的诊治方案以惠及更广泛的患者。目前，全球范围内尚无治疗晚期ESCC的EGFR靶向药物获批上市。 HLX07-ESCC201研究结果首次于2023年6月在2023年美国临床肿瘤学会（ASCO）年会发布[4]。该研究为一项开放标签、多中心的II期研究。试验纳入年龄为18–75岁、经组织学或细胞学确认的局部晚期、不可切除/转移性ESCC或食管腺鳞癌患者。既往未接受过全身抗肿瘤治疗的患者被分配至A组，给予HLX07 1000 mg（抗EGFR单克隆抗体）联合斯鲁利单抗200 mg（抗PD-1单克隆抗体）及化疗（5-FU 2400 mg/m2 + 顺铂50 mg/m2），每两周一次静脉输注。一线免疫联合化疗治疗失败或至少两种其他系统性抗肿瘤治疗失败的患者被分配至B组，并给予HLX07单药治疗（1000 mg，每两周一次静脉输注）。试验的主要终点是由独立影像评估委员会（IRRC）和研究者根据RECIST v1.1评估的客观缓解率（ORR）和无进展生存期（PFS）。本次发表于Cancer Communications的数据截止日期为2023年7月4日，共50例患者入组至A组（n = 30）和B组（n = 20），IRRC评估的ORR分别为60%（95% CI 40.6–77.3%）和15.0%（95% CI 3.2–37.9%）；中位PFS分别为7.8个月（95% CI 3.3–9.1）和1.5个月（95% CI 1.3–3.7）；中位持续缓解时间（DOR）在B组中未达到（>6个月），在A组中为7.2个月（95% CI 4.4–不可评估）。研究结果显示，HLX07单药或联合H药（斯鲁利单抗）及化疗治疗复发性或转移性ESCC患者均显示出可控的毒性和良好的抗肿瘤活性，为HLX07针对ESCC的后续临床研究开展奠定了基础[5]。 HLX07是复宏汉霖自主研发的针对EGFR靶点的创新型生物药。基于公司成熟的抗体工程改造平台，复宏汉霖在西妥昔单抗的基础上，将HLX07的Fab区人源化，同时使该产品聚糖含量降至最低，以具备更低的免疫原性和良好的靶点亲和力。复宏汉霖已就HLX07在中国、美国、欧盟、澳大利亚、日本等多个知识产权区获得专利，并在中国和美国获得临床试验许可。目前，公司围绕食管鳞癌、皮肤鳞癌、鼻咽癌等多个实体瘤适应症，正在积极开展HLX07单药或联合H药 汉斯状®（斯鲁利单抗）的II期临床探索。 未来，复宏汉霖将持续加码创新，以临床需求为先导，继续高效地为全球患者提供更多可负担、疗效更好的治疗方案。 【参考文献】 [1] Arnold, M., Ferlay, J., van Berge Henegouwen, M.I. & Soerjomataram, I. Global burden of oesophageal and gastric cancer by histology and subsite in 2018. Gut 69, 1564-1571 (2020). [2] Zheng, R., Zhang, S., Zeng, H., et al. Cancer incidence and mortality in China, 2016. Journal of the National Cancer Center 2, 1-9 (2022). [3] 食管癌诊疗指南（2022年版）. 中国国家卫生健康委员会. [4] Huang J, Liu Y, Wu T, et al. A phase 2 study of HLX07 as monotherapy or combination therapy in patients with locally advanced, unresectable, or metastatic esophageal squamous cell carcinoma. Journal of Clinical Oncology. Volume 41, Number 16_suppl [5] Liu Y, Wang Y, Zhu Y, et al. HLX07 alone or combined with serplulimab, cisplatin and 5-fluorouracil for advanced esophageal squamous cell carcinoma: A phase 2 study. Cancer Commun (Lond). Published online October 24, 2024. doi:10.1002/cac2.12621 Cancer Communications Published the Results of HLX07-ESCC201: HLX07 as monotherapy or combination therapy in ESCC Recently, the results from the phase 2 study (HLX07-ESCC201) of HLX07, the company’s innovative humanised anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in patients with locally advanced, unresectable, or metastatic esophageal squamous cell carcinoma (ESCC) were published in Cancer Communications (2023 impact factor: 20.1). The study was led by Professor Jing Huang from the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Esophageal cancer is one of the most common malignancies worldwide, and can be mainly classified as squamous cell carcinoma and adenocarcinoma, with ESCC accounting for more than 84% of esophageal cancer. [1] Esophageal cancer is highly prevalent in China; according to the estimates of cancer incidence and mortality in China in 2016, there were 252,500 new cases and 193,900 deaths related to esophageal cancer, ranking sixth and fifth in all malignant tumours in China, respectively. [2] As the symptoms of early esophageal cancer are often subtle, most patients are often diagnosed at mid- to late-stage, therefore missing out on surgical treatment. The main treatment for advanced patients is systemic treatment with chemotherapy or targeted therapy, but with limited efficacy, high recurrence and metastatic rate. Therefore, the development of new drugs and treatments are urgently needed. In recent years, immuno-oncology therapy has become one of the research priorities globally. Many studies have shown that anti-PD-1 mAb combined with chemotherapy can bring about survival benefits to patients with esophageal cancer. Immune checkpoint inhibitor, such as serplulimab, combined with chemotherapy has become the standard first-line treatment for advanced esophageal cancer in China.[3] However, there is still a need to explore more diverse treatment to benefit a broader range of patients. To date, no approval has been granted for the use of EGFR targeted drugs in advanced ESCC. The results of the HLX07-ESCC201 study were first released in June 2023 at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.[4] In this open-label, multicentre phase 2 study, patients aged 18–75 years with histologically or cytologically confirmed locally advanced, unresectable/metastatic esophageal squamous cell carcinoma or esophageal adenosquamous carcinoma were enrolled. Patients with no prior systemic antitumour therapy were assigned to group A and given HLX07 1000 mg (anti-EGFR monoclonal antibody) plus serplulimab 200 mg (anti-PD-1 monoclonal antibody) and chemotherapy (5-FU 2400 mg/m2 + cisplatin 50 mg/m2), Q2W IV. Patients who had failed first-line immuno-chemotherapy combination or at least two lines of other systemic antitumor therapy were assigned to group B and given HLX07 monotherapy (1000 mg Q2W IV). The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) assessed by an independent radiological review committee and investigators per RECIST v1.1. The data cut-off date for this publication in Cancer Communications is July 4, 2023. A total of 50 patients were enrolled in Group A (n = 30) and Group B (n = 20). The ORRs assessed by IRRC were 60% (95% CI 40.6–77.3%) and 15.0% (95% CI 3.2–37.9%) in the respective groups. The median PFSs were 7.8 months (95% CI 3.3–9.1) and 1.5 months (95% CI 1.3–3.7), respectively. IRRC-assessed median duration of response (DOR) was not reached in group B (>6 months) and 7.2 months (95% CI 4.4–not evaluable) in group A. The findings indicate that HLX07 monotherapy and its combination with serplulimab and chemotherapy showed manageable toxicity and promising antitumor activity in patients with recurrent or metastatic ESCC. Randomised controlled trials are warranted to further establish the safety and efficacy of HLX07 against ESCC.[5] HLX07 is an innovative drug targeting EGFR independently developed by Henlius. Adopting the self-developed advanced antibody engineering platform, Henlius re-engineered cetuximab by humanising its Fab regions and minimizing its glycan contents to generate HLX07 to reduce immunogenicity and maintain a high binding affinity of the product. To date, Henlius holds patents of HLX07 in several jurisdictions including China, the United States, the European Union, Australia, and Japan. Currently, Henlius is conducting phase 2 clinical trials to explore HLX07 as monotherapy or in combination with HANSIZHUANG (serplulimab) for the treatment of solid tumours including ESCC, cutaneous squamous cell carcinoma (CSCC), and nasopharyngeal carcinoma (NPC).  Looking forward, Henlius will actively improve efficiency through innovations, focusing on unmet medical needs to bring more high-quality and affordable therapies to patients worldwide.   About Henlius Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable, and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases, and ophthalmic diseases. Up to date, 6 products have been launched in China, 3 have been approved for marketing in overseas markets, 24 indications are approved worldwide, and 4 marketing applications have been accepted for review in China, the U.S. and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP. Henlius has pro-actively built a diversified and high-quality product pipeline covering over 50 molecules and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as backbone. Apart from the launched products HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANDAYUAN (adalimumab), HANBEITAI (bevacizumab) and HANNAIJIA (neratinib), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC), making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. What’s more, Henlius has conducted over 30 clinical studies for 16 products, expanding its presence in major markets as well as emerging markets. 联系方式 媒体：PR@Henlius.com 投资者：IR@Henlius.com 喜欢本文内容 点击下方按钮·分享 ·收藏 ·点赞 ·在看