2025年9月30日，复宏汉霖（2696.HK）宣布，公司创新型程序性死亡-配体1（PD-L1）抗体偶联药物（ADC）注射用HLX43联合其自研的重组抗EGFR单克隆抗体HLX07用于晚期/转移性实体瘤治疗的Ib/II 期临床研究获中国国家药品监督管理局（NMPA）批准。这是针对HLX43开展的第二项联合治疗方案。
HLX43是一款潜在同类最优（Best-in-class）的PD-L1 ADC，由全人源IgG1抗PD-L1抗体与创新连接子-拓扑异构酶抑制剂荷载偶联而成，药物抗体比（drug-to-antibody ratio, DAR）约为8。临床前研究显示，HLX43在PD-1/PD-L1单抗耐药的非小细胞肺癌、宫颈癌、食管鳞癌等多个瘤种中展现出治疗潜力，且耐受性良好。在早期临床研究中，HLX43展现出高效、低毒、兼具IO功能的广谱抗肿瘤潜力，不依赖患者PD-L1表达。其在2025 WCLC上公布的最新临床研究数据进一步验证了HLX43在扩大患者样本中优异的抗肿瘤疗效，尤其在EGFR野生型等特定亚组人群中疗效更为凸显，EGFR野生型非鳞状NSCLC患者的经确认的客观缓解率为46.7%，其中2.5mg/kg剂量组疗效更为显著，ORR达60.0%，且安全性良好。
HLX07是复宏汉霖自主开发的创新型抗EGFR的单抗。相比西妥昔单抗该产品具备更低的免疫原性和更好的靶点亲和力。同时通过Fc端改造，HLX07大大延长了产品的半衰期，3周的给药频率使其更适合与肿瘤免疫产品的临床联用。临床前研究表明，HLX07具有出色的生物活性，在不同肿瘤模型中均能显著抑制肿瘤细胞的生长，并与H药显示出很强的协同作用[1]。基于此，复宏汉霖围绕肺鳞癌、皮肤鳞癌、鼻咽癌、食管鳞癌等多个实体瘤适应症，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。
根据2025 WCLC最新数据发布，HLX07联合斯鲁利单抗及化疗在EGFR高表达sqNSCLC患者一线治疗中展现出显著的抗肿瘤活性和持久疗效，在中位随访18.6个月时，两个剂量组均实现了约70%的客观缓解率（ORR）和超过90%的疾病控制率（DCR）；其中高剂量组的中位无进展生存期（PFS）达到17.4个月，由于大部分低剂量组患者的病情仍在稳定控制中，尚无法得出低剂量组的中位无进展生存期(PFS)，显示出疗效的持续性，表明抗EGFR单抗与PD-1/L1抑制剂的联用，不仅阻断EGFR生长信号，更同步激活免疫应答，极具联合协同治疗潜力。此外，传统拓扑异构酶抑制剂和抗EGFR 抗体联合用药的疗效已在临床研究中得到验证。已有研究表明，西妥昔单抗与伊立替康（一类拓扑异构酶抑制剂）的联合疗法在转移性结直肠癌的治疗中展现出显著优势，其疗效优于西妥昔/化疗单药治疗[2]，目前已获批用于该病的一线及后线治疗[3-4]。此外，“抗EGFR抗体+化疗”的联合策略也广泛应用于结直肠癌、头颈鳞癌、胰腺癌等多种实体瘤的治疗[4-6]。因此，兼具抗PD-L1单抗的肿瘤免疫治疗（IO）与拓扑异构酶抑制剂的毒素精准杀伤功能的HLX43，有望协同抗EGFR单抗HLX07，发挥出较拓扑异构酶抑制剂联合抗EGFR单抗更高的治疗潜力，进一步提升晚期实体瘤患者的治疗获益。
目前，复宏汉霖正全力推进HLX43的临床开发进程，累计已启动十项HLX43单药及联合其他产品的临床研究，广泛覆盖非小细胞肺癌（NSCLC）、胸腺癌（TC）、宫颈癌、肝细胞癌、食管鳞癌、头颈鳞癌、鼻咽癌、结直肠癌、胃癌/胃食管交界部（G/GEJ）癌等。其中，HLX43针对NSCLC、TC等实体瘤的国际多中心II期临床陆续在中美日澳等地启动。基于HLX43展现出的IO疗效，一项探索HLX43联用公司自研抗PD-1单抗H药 斯鲁利单抗（汉斯状®）用于实体瘤治疗的Ib/II期联合治疗方案正在进行中。此外,公司积极探索HLX43与其他多元分子的联合治疗潜力，不断挖掘和最大化该产品在临床中的应用价值。
未来，复宏汉霖将继续秉持“以患者为中心”的初心和理念，深耕实体瘤这一重要疾病领域，通过不断挖掘患者未满足的临床需求，持续夯实更多创新分子的差异化布局，为更多肿瘤患者带来高质量、可负担的新型治疗方案。
【参考文献】
[1] Tseng,Yun-Chih Cheng, Chieh-Hsin Ho, Shih Chieh Chen, Yanling Wang, Eugene Liu,Hassan Issafras & Weidong Jiang (2021) Distinguishing features of a novelhumanized anti-EGFR monoclonal antibody based on cetuximab with superiorantitumor efficacy, Expert Opinion on Biological Therapy, 21:11, 1491-1507.
[2] D Cunningham, Y Humblet, S Siena et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004, 351: 337-345
[3] E Van Cutsem, CH Köhne, E Hitre et al. Cetuximab and chemotherapy as initial treatment formetastatic colorectal cancer. N Engl J Med. 2009, 360: 1408-1417.
[4] I LLC. Cetuximab FDA label. 2021.09.24.
[5] A Inc. Panitumumab FDA label. 2025.01.16.
[6] 尼妥珠单抗注射液说明书. 2017.12.12.
关于复宏汉霖
复宏汉霖（2696.HK）是一家国际化的创新生物制药公司，致力于为全球患者提供可负担的高品质生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域，已在全球获批上市9款产品，4个上市申请分别获中国药监局、美国FDA和欧盟EMA受理。自2010年成立以来，复宏汉霖已建成一体化生物制药平台，高效及创新的自主核心能力贯穿研发、生产及商业运营全产业链。公司已建立完善高效的全球创新中心，按照国际药品生产质量管理规范（GMP）标准进行生产和质量管控，不断夯实一体化综合生产平台，其中，公司商业化生产基地已相继获得中国、欧盟和美国GMP认证。
复宏汉霖前瞻性布局了一个多元化、高质量的产品管线，涵盖约50个分子，并全面推进基于自有抗PD-1单抗H药汉斯状®的肿瘤免疫联合疗法。截至目前，公司已获批上市产品包括全球首个获批一线治疗小细胞肺癌的抗PD-1单抗汉斯状®（斯鲁利单抗，欧洲商品名：Hetronifly®）、自主研发的中美欧三地获批单抗生物类似药汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™，欧洲商品名：Zercepac®）、国内首个生物类似药汉利康®（利妥昔单抗）、以及地舒单抗生物类似药Bildyos®和Bilprevda®。公司亦同步就19个产品在全球范围内开展30多项临床试验，对外授权全面覆盖欧美主流生物药市场和众多新兴市场。
Henlius Receives the NMPA IND Approval for Its PD-L1-Targeting ADC HLX43 in Combination with Novel Anti-EGFR mAb HLX07
Shanghai, China, September 30, 2025—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 innovative programmed death-ligand 1 (PD-L1) targeting antibody-drug conjugate (ADC), in combination with the company's independently developed innovative anti-EGFR monoclonal antibody (mAb) HLX07, has been approved by the China National Medical Products Administration (NMPA), for the treatment of advanced/metastatic solid tumors. This represents the second combination therapy developed for HLX43.
HLX43 is a potential best-in-class PD-L1-targeted ADC, which is composed of a fully humanized anti-PD-L1 IgG1 antibody, a novel tripeptide linker and topoisomerase inhibitor payload. The drug-to-antibody ratio (DAR) is around 8. Preclinical data have shown that, HLX43 exerts potent anti-tumor effects with a favorable tolerability profile in non-small cell lung cancer (NSCLC), cervical cancer (CC), esophageal squamous cell carcinoma (ESCC), and other tumor types that were PD-1/L1 mAb-resistant. In early-stage clinical trial, HLX43 demonstrates promising broad-spectrum antitumor activity with a favorable safety profile. It mediates a dual mechanism of action integrating immune checkpoint inhibition with targeted cytotoxic payload delivery, and exhibits efficacy independent of PD-L1 expression status. Updated 2025 WCLC data confirms its outstanding anti-tumor efficacy in an expanded cohort, particularly in subgroups such as EGFR wild-type NSCLC, where a confirmed objective response rate (cORR) was 46.7% for EGFR wild-type non-squamous NSCLC, and 60.0% for those receiving HLX43 at 2.5 mg/kg.
HLX07 is an innovative anti-EGFR mAb developed by Henlius. Compared with cetuximab, HLX07 demonstrates lower immunogenicity and higher target affinity. Fc engineering extends its half-life, enabling every-3-week dosing that facilitates combination with immuno-oncology agents. Preclinical studies showed synergistic antitumor activity of HLX07 with the anti-PD-1 mAb serplulimab across tumor models [1]. Accordingly, Henlius is conducting phase 2 clinical trials to explore HLX07 as monotherapy or in combination with serplulimab for the treatment of solid tumors including squamous non-small cell lung cancer (sqNSCLC), cutaneous squamous cell carcinoma (CSCC), nasopharyngeal carcinoma (NPC) and ESCC.
According to the updated results in 2025 WCLC, the combination of HLX07 with serplulimab and chemotherapy demonstrated remarkable antitumor activity and durable efficacy as first-line treatment for patients with EGFR overexpression sqNSCLC. At a median follow-up of 18.6 months, both dose groups achieved an objective response rate (ORR) of around 70% and a disease control rate (DCR) of over 90%. The median progression-free survival (PFS) reached 17.4 months in the high-dose group. The median progression-free survival (PFS) in the low-dose group has not yet been reached, as most patients continue to exhibit stable disease, underscoring the enduring treatment effect.This indicates that the combination of HLX07 and serplulimab blocks EGFR signaling while activating immune responses, supporting strong therapeutic synergy.
Studies have demonstrated that the combination of cetuximab and irinotecan (a topoisomerase inhibitor) is superior to either agent alone in metastatic colorectal cancer (mCRC)[2]. This combination is approved for both first-line and later-line treatment of mCRC[3-4]. Furthermore, this "anti-EGFR antibody plus chemotherapy" strategy is now widely used for various solid tumors, including colorectal, head and neck squamous cell carcinoma (HNSCC), and pancreatic cancers[4-6].
Therefore, HLX43 integrates the immuno-oncology (IO) activity of an anti-PD-L1 mAb with the targeted cytotoxicity of a topoisomerase inhibitor, potentially synergizing with the anti-EGFR mAb HLX07 to demonstrate superior efficacy over conventional topoisomerase inhibitor plus anti-EGFR antibody regimens, thereby providing enhanced clinical benefits for patients with advanced solid tumors.
Currently, Henlius is vigorously advancing the clinical development of HLX43, with its therapeutic potential currently being explored across 10 clinical studies in various solid tumors, including NSCLC, thymic carcinoma (TC), CC, hepatocellular carcinoma (HCC), ESCC, head and neck squamous cell carcinoma (HNSCC), NPC, colorectal cancer (CRC), and gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Among these, the multi-regional clinical trials (MRCTs) of HLX43 in NSCLC and TC and other solid tumors have been initiated across China, the U.S., Australia and Japan. Based on the promising immuno-oncology (IO) effect demonstrated by HLX43, a phase 1b/2 clinical trial to evaluate its combination therapy with serplulimab in patients with solid tumors is underway. Furthermore, the company is actively exploring the therapeutic potential of HLX43 in combination with other agents to fully maximize its clinical value.
By strategically prioritizing solid tumor domain as a core therapeutic area, Henlius continues to uphold its patient-centric mission, accelerating differentiated innovation to address unmet medical needs and delivering high-quality, affordable therapies to tumor 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. To date, 9 products have been approved for marketing across multiple countries and regions, 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 about 50 molecules and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as the backbone. To date, the company's launched products include HANSIZHUANG (serplulimab, trade name: Hetronifly in Europe), the world’s first anti-PD-1 mAb for the first-line treatment of SCLC, HANQUYOU (trastuzumab, trade name: HERCESSI in the U.S., Zercepac in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANLIKANG (rituximab), the first China-developed biosimilar, and denosumab BILDYOS and BILPREVDA. What’s more, Henlius has conducted over 30 clinical studies for 19 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
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