全球研发 | 全球首个胸腺上皮肿瘤治疗ADC！复宏汉霖PD-L1 ADC HLX43获美国FD...

（来源：复星医药）

转自：复星医药

• HLX43获得FDA孤儿药资格认定用于胸腺上皮肿瘤的治疗，意味着该产品后续在美国的研发、注册及商业化等方面将享受一定的政策支持

• 胸腺癌是胸腺上皮肿瘤中一类相对罕见但侵袭性强、预后较差的恶性肿瘤，现有后线治疗方案疗效不佳，存在较大的未满足临床需求

• HLX43是全球首个布局胸腺上皮肿瘤的PD-L1 ADC，在胸腺癌患者的后线治疗中展现出优异的初步疗效，有望填补该疾病 ADC治疗的空白

2025年10月20日，复星医药子公司复宏汉霖（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已获得美国食品药品监督管理局（FDA）授予的孤儿药资格认定（Orphan Drug Designation, ODD），用于胸腺上皮肿瘤（Thymic Epithelial Tumors，TETs）的治疗。

美国HLX43胸腺研究主要研究者、芝加哥大学医学中心教授Marina Garassino博士表示

胸腺上皮肿瘤是一种仍然充满挑战且研究相对不足的疾病，尤其后线胸腺癌患者目前尚缺乏有效的治疗手段。HLX43在临床试验中展现出的令人鼓舞的初步疗效，为晚期胸腺上皮肿瘤患者带来了新的希望。很高兴见到这款创新型PD-L1抗体偶联药物获得美国FDA孤儿药资格认定，这一里程碑进一步印证了其在满足重大临床需求方面的潜力。

获得FDA孤儿药资格认定的药物将享有包括但不限于 1)临床试验费用的税收抵免,2)免除新药申请费,3)获批后七年的市场独占权等一系列政策支持，以加速其开发进程，早日惠及患者。HLX43是全球首个布局胸腺上皮肿瘤的PD-L1 ADC，其I期临床研究在胸腺癌（Thymic Carcinoma）等实体瘤中展现出“高效、低毒”的治疗潜力（2025 ASCO：75%的胸腺癌患者达到部分缓解，ORR=75%）。基于此，公司高效推进HLX43在中、美、日、澳等地的国际多中心临床研究，其用于TC治疗已获得中国、美国、日本等地监管机构的临床试验许可。此次获FDA授予孤儿药资格认定是HLX43全球开发进程中的又一重要里程碑，意味着该产品在胸腺上皮肿瘤领域的突破性治疗潜力获得国际权威机构认可，有望进一步缩短HLX43的全球开发周期，加速填补该疾病ADC治疗的空白。

胸腺上皮肿瘤是起源于胸腺上皮细胞的一类相对罕见的肿瘤，为前纵隔最常见的原发性肿瘤。世界卫生组织（WHO）将其主要分为胸腺瘤（Thymoma）、胸腺癌（Thymic Carcinoma）以及胸腺神经内分泌肿瘤等亚型[1-2]。其中，胸腺癌约占所有胸腺上皮肿瘤的14%-22%[3]，该疾病呈现高侵袭性特征，如局部浸润、胸内淋巴结和远处转移，且预后较差[4]。其病理亚型以鳞状细胞癌（squamous cell carcinoma）为主，占比约70%，其次为淋巴上皮癌、未分化癌等[5]。流行病学研究显示，该疾病中位发病年龄为50-60岁[3]，全球年发病率稳定在0.15/10万，但近年诊断率呈上升趋势[4]。对于早期局限性胸腺癌，手术切除是首选治疗方法。对于晚期或复发转移患者，一线治疗主要为联合化疗方案，二线治疗包括化疗、靶向治疗、免疫治疗等系统治疗。但现有治疗方案存在各种局限，如缺少驱动基因、耐药机制复杂、不良反应严重等，且整体疗效有限，亟待更加安全且有效的新型治疗方案[6-10]。

HLX43是一款潜在BIC的广谱抗肿瘤ADC，兼具免疫检查点阻断与载荷细胞毒性的双重作用机制。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。I期临床数据提示，HLX43在NSCLC、TC等实体瘤中展现出“高效、低毒”的显著疗效，且对于鳞状/非鳞状NSCLC，有无EGFR突变、有无脑/肝转移、PD-L1阳性/阴性的NSCLC患者人群都具有疗效，不依赖生物标志物筛选。根据2025 WCLC上公布的最新临床研究数据，HLX43在扩大的患者样本中持续验证了其在晚期非小细胞肺癌（NSCLC）等实体瘤中的优异疗效，尤其在EGFR野生型NSCLC等特定亚组人群中疗效更为凸显，且安全性良好。值得关注的是，HLX43在PD-L1阴性（TPS＜1%）患者群体中展现了差异化的治疗潜力，ORR和DCR分别达到38.1%和85.7%，提示HLX43疗效不受PD-L1表达限制，有望覆盖更广泛的患者群体。

目前，公司正全力推进HLX43的临床开发进程，已在全球入组超过400例患者，并在中国、美国、日本、澳大利亚等多国顺利推进患者入组。公司持续挖掘HLX43在多种实体瘤中的治疗潜力，共计开设10项针对HLX43的临床研究，广泛覆盖非小细胞肺癌、胸腺癌、宫颈癌、肝细胞癌、食管鳞癌、头颈鳞癌、鼻咽癌、结直肠癌、胃癌/胃食管交界部癌等。单药之外，HLX43联用其他产品的临床试验也正在进行中，进一步探索“ADC+IO”的协同抗肿瘤疗效。

未来，随着HLX43在后线实体瘤患者中的疗效逐步得到验证，复宏汉霖也将持续将产品推向更前线的治疗，加速为更多晚期/转移性实体瘤患者带来疗效优异的新型治疗选择。

【参考文献】

[1] Detterbeck F C, Parsons A M. Thymic tumors: A review of current diagnosis, classification, and treatment[M]. 2008.

[2] 国际胸腺恶性肿瘤协作组织(ITMIG)关于胸腺瘤和胸腺癌的WHO组织学分类的共识

[3] Luis Cabezón-Gutiérrez, et al. Update on thymic epithelial tumors: a narrative review. Mediastinum 2024;8:33.

[4] Hsu, C. H. et al. Trends in the incidence of thymoma, thymic carcinoma, and thymic neuroendocrine tumor in the United States. PLoS One 14, e0227197.

[5] World Health Organization. WHO Classification of Tumors Online, Thoracic Tumors, Tumors of the Thymus, 5th ed.; World Heath Organization: Geneva, Switzerland 2021. Available online: https://tumorclassification.iarc. who.int/chapters/35.

[6] 中国医师协会肿瘤多学科诊疗专业委员会. 中国胸腺上皮肿瘤临床诊疗指南(2021版) %J 中华肿瘤杂志. 395-404 (2021).

[7] He, Y., Ramesh, A., Gusev, Y., Bhuvaneshwar, K. & Giaccone, G. Molecular predictors of response to pembrolizumab in thymic carcinoma. Cell Rep Med 2, 100392,

[8] Zhang, Y. et al. Thymoma and Thymic Carcinoma: Surgical Resection and Multidisciplinary Treatment. Cancers 15

[9] Zhang, C. et al. The Prognostic Value of Postoperative Radiotherapy for Thymoma and Thymic Carcinoma: A Propensity-Matched Study Based on SEER Database. Cancers 14

[10] Kaira, K., Imai, H. & Kagamu, H. Perspective of Immune Checkpoint Inhibitors in Thymic Carcinoma. Cancers 13

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 Orphan Drug Designation for PD-L1 ADC HLX43 in the U.S. for Thymic Epithelial Tumors

• FDA's grant of ODD for HLX43 in Thymic Epithelial Tumors (TETs) marks another milestone in its global development, qualifying it for certain incentives in R&D, registration, and commercialization in the U.S.

• Thymic Carcinoma (TC) is a relatively rare yet highly aggressive subtype of TETs with a poor prognosis. Current later-line treatments show limited efficacy, indicating a significant unmet medical need for this disease

• As the world's first PD-L1 ADC developed for TETs, HLX43 has demonstrated promising preliminary efficacy in the later-line treatment of patients with TC. It is positioned to address the unmet clinical need for ADC therapies in this rare and highly aggressive malignancy

Shanghai, China, October 20, 2025 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for HLX43, the company's innovative programmed death-ligand 1 (PD-L1) targeting antibody-drug conjugate (ADC), for the treatment of thymic epithelial tumors (TETs).

Dr. Marina Garassino, MD, Professor of Medicine at the University of Chicago and leading principal investigator of the HLX43 Thymic Study in the U.S., said:“Thymic epithelial tumors remain a challenging and understudied disease area, especially for patients with advanced thymic carcinoma who currently have very limited treatment options. The encouraging preliminary efficacy observed with HLX43 brings new hope to patients with advanced thymic epithelial tumors. I’m pleased to see this innovative PD-L1 ADC receiving Orphan Drug Designation from the U.S. FDA, a milestone that further validates its potential to address a significant unmet medical need.”

According to the U.S. FDA, the drug or biological product receives an ODD will be eligible for certain development incentives, including but not limited to: 1) tax credits for clinical trial costs; 2) waiver of BLA user fees for new drugs; and 3) seven years of market exclusivity without being affected by patent, aiming to accelerate the development process so that patients can benefit from the products as soon as possible. HLX43 is the world's first PD-L1-targeting ADC developed for TETs. Its phase 1 clinical data released at 2025 ASCO has demonstrated "high efficacy with low toxicity" in solid tumors such as thymic carcinoma (TC)，with an ORR of 75% in TC patients. Regarding this indication, the company is accelerating multicenter studies of HLX43 in China, the U.S., Japan, and Australia to expedite its global launch to benefit broader patient populations. Receiving an ODD for HLX43 signifies international recognition of its breakthrough therapeutic potential to treat patients with TETs and marks another milestone in its global development, positioned to address the unmet medical need for ADC treatments in this rare and aggressive malignancy.

Thymic epithelial tumors (TETs) are a group of relatively rare tumors originating from thymic epithelial cells and represent the most common primary tumors of the anterior mediastinum. The World Health Organization (WHO) classifies them into various subtypes, primarily including thymomas, thymic carcinomas, and thymic neuroendocrine tumors [1-2]. Among these, thymic carcinoma (TC) accounts for approximately 14% to 22% of all TETs [3]. It is characterized by high aggressiveness, including local infiltration, intrathoracic lymph node involvement, and distant metastases, and is associated with a relatively poor prognosis[4]. Histopathologically, thymic squamous cell carcinoma (TSCC) constitutes the predominant subtype (∼70%), followed by lymphoepithelial carcinoma and undifferentiated carcinoma [5]. Epidemiological studies indicate a median age at diagnosis of 50-60 years [3], with a stable global annual incidence of 0.15 per 100,000 person-years; however, increasing diagnostic rates have been observed in recent years [4]. For localized early-stage patients, surgical resection remains the primary therapeutic approach, while advanced or recurrent/metastatic cases require first-line platinum-based combination chemotherapy followed by second-line systemic therapies (including chemotherapy, targeted therapies, and immunotherapy). Critical therapeutic limitations persist, including lack of actionable driver mutations, complex drug resistance mechanisms, significant treatment-related toxicities, and suboptimal efficacy, underscoring the urgent unmet medical need for safer and more effective novel treatment strategies [6-10].

HLX43 is a broad-spectrum anti-tumor ADC candidate targeting PD-L1, which exhibits dual mechanisms integrating immune checkpoint blockade and payload-mediated cytotoxicity. Preclinical data have shown that, HLX43 has good anti-tumor effects and a favorable tolerability profile in NSCLC, cervical cancer (CC), esophageal squamous cell carcinoma (ESCC), and other tumor types that were PD-1/L1 mAb-resistant. The results from the phase 1 clinical trial of HLX43 has been first released at the 2025 ASCO Annual Meeting, demonstrating manageable safety profile and encouraging efficacy in various solid tumors especially in patients with NSCLC, including squamous and non-squamous NSCLC patients (sqNSCLC and nsqNSCLC), patients with or without EGFR mutation, patients with or without brain/liver metastasis, and PD-L1 positive or negative patients.

According to updated data released at the 2025 WCLC, HLX43 continues to demonstrate superior efficacy in an expanded cohort of NSCLC patients, and highlights its therapeutic potential in specific subgroups such as EGFR wild-type NSCLC patients. Confirmed objective response rate (cORR) was 46.7% for patients with an EGFR wild-type non-squamous NSCLC. Among these patients, cORR was 60.0% for those receiving HLX43 at 2.5 mg/kg, along with a favorable safety profile. Notably, HLX43 exhibits robust efficacy in PD-L1 negative (TPS <1%) patients, with an ORR of 38.1% and DCR of 85.7%, indicating its differentiated therapeutic potential to cover a broader patient population regardless of PD-L1 expression.

Currently, Henlius is advancing the clinical development of HLX43 at full speed, with over 400 patients enrolled globally and patient recruitment progressing smoothly in multiple countries including China, the U.S., Japan and Australia. Additionally, the company is actively exploring HLX43's therapeutic potential across 10 clinical studies in various solid tumors, including NSCLC, TC, cervical cancer (CC), hepatocellular carcinoma (HCC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC), nasopharyngeal cancer (NPC), colorectal cancer (CRC), and gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Both monotherapy and combination therapies of HLX43 are ongoing simultaneously to further exploit the synergistic effects of ADC-mediated cytotoxicity and other agents.

As HLX43's efficacy validated in later-line treatment of NSCLC, Henlius will further promote the front-line regimens for HLX43, accelerating the delivery of this novel treatment option to more patients with advanced or metastatic solid tumors.

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.