全球研發 | 全球首個胸腺上皮腫瘤治療ADC！復宏漢霖PD-L1 ADC HLX...

• HLX43獲得FDA孤兒藥資格認定用於胸腺上皮腫瘤的治療，意味着該產品后續在美國的研發、註冊及商業化等方面將享受一定的政策支持

• 胸腺癌是胸腺上皮腫瘤中一類相對罕見但侵襲性強、預后較差的惡性腫瘤，現有后線治療方案療效不佳，存在較大的未滿足臨牀需求

• HLX43是全球首個佈局胸腺上皮腫瘤的PD-L1 ADC，在胸腺癌患者的后線治療中展現出優異的初步療效，有望填補該疾病 ADC治療的空白

2025年10月20日，復星醫藥子公司復宏漢霖（2696.HK）宣佈，公司創新型程序性死亡-配體1（PD-L1）抗體偶聯藥物（ADC）注射用HLX43已獲得美國食品藥品監督管理局（FDA）授予的孤兒藥資格認定（Orphan Drug Designation, ODD），用於胸腺上皮腫瘤（Thymic Epithelial Tumors，TETs）的治療。

 

美國HLX43胸腺研究主要研究者、芝加哥大學醫學中心教授Marina Garassino博士表示

胸腺上皮腫瘤是一種仍然充滿挑戰且研究相對不足的疾病，尤其后線胸腺癌患者目前尚缺乏有效的治療手段。HLX43在臨牀試驗中展現出的令人鼓舞的初步療效，為晚期胸腺上皮腫瘤患者帶來了新的希望。很高興見到這款創新型PD-L1抗體偶聯藥物獲得美國FDA孤兒藥資格認定，這一里程碑進一步印證了其在滿足重大臨牀需求方面的潛力。

獲得FDA孤兒藥資格認定的藥物將享有包括但不限於 1)臨牀試驗費用的税收抵免,2)免除新葯申請費,3)獲批后七年的市場獨佔權等一系列政策支持，以加速其開發進程，早日惠及患者。HLX43是全球首個佈局胸腺上皮腫瘤的PD-L1 ADC，其I期臨牀研究在胸腺癌（Thymic Carcinoma）等實體瘤中展現出「高效、低毒」的治療潛力（2025 ASCO：75%的胸腺癌患者達到部分緩解，ORR=75%）。基於此，公司高效推進HLX43在中、美、日、澳等地的國際多中心臨牀研究，其用於TC治療已獲得中國、美國、日本等地監管機構的臨牀試驗許可。此次獲FDA授予孤兒藥資格認定是HLX43全球開發進程中的又一重要里程碑，意味着該產品在胸腺上皮腫瘤領域的突破性治療潛力獲得國際權威機構認可，有望進一步縮短HLX43的全球開發周期，加速填補該疾病ADC治療的空白。

胸腺上皮腫瘤是起源於胸腺上皮細胞的一類相對罕見的腫瘤，為前縱隔最常見的原發性腫瘤。世界衞生組織（WHO）將其主要分為胸腺瘤（Thymoma）、胸腺癌（Thymic Carcinoma）以及胸腺神經內分泌腫瘤等亞型[1-2]。其中，胸腺癌約佔所有胸腺上皮腫瘤的14%-22%[3]，該疾病呈現高侵襲性特徵，如局部浸潤、胸內淋巴結和遠處轉移，且預后較差[4]。其病理亞型以鱗狀細胞癌（squamous cell carcinoma）為主，佔比約70%，其次為淋巴上皮癌、未分化癌等[5]。流行病學研究顯示，該疾病中位發病年齡為50-60歲[3]，全球年發病率穩定在0.15/10萬，但近年診斷率呈上升趨勢[4]。對於早期侷限性胸腺癌，手術切除是首選治療方法。對於晚期或復發轉移患者，一線治療主要為聯合化療方案，二線治療包括化療、靶向治療、免疫治療等系統治療。但現有治療方案存在各種侷限，如缺少驅動基因、耐藥機制複雜、不良反應嚴重等，且整體療效有限，亟待更加安全且有效的新型治療方案[6-10]。

HLX43是一款潛在BIC的廣譜抗腫瘤ADC，兼具免疫檢查點阻斷與載荷細胞毒性的雙重作用機制。臨牀前研究顯示，HLX43在PD-1/PD-L1單抗耐藥的非小細胞肺癌、宮頸癌、食管鱗癌等多個瘤種中展現出治療潛力，且耐受性良好。I期臨牀數據提示，HLX43在NSCLC、TC等實體瘤中展現出「高效、低毒」的顯著療效，且對於鱗狀/非鱗狀NSCLC，有無EGFR突變、有無腦/肝轉移、PD-L1陽性/陰性的NSCLC患者人羣都具有療效，不依賴生物標誌物篩選。根據2025 WCLC上公佈的最新臨牀研究數據，HLX43在擴大的患者樣本中持續驗證了其在晚期非小細胞肺癌（NSCLC）等實體瘤中的優異療效，尤其在EGFR野生型NSCLC等特定亞組人羣中療效更為凸顯，且安全性良好。值得關注的是，HLX43在PD-L1陰性（TPS＜1%）患者羣體中展現了差異化的治療潛力，ORR和DCR分別達到38.1%和85.7%，提示HLX43療效不受PD-L1表達限制，有望覆蓋更廣泛的患者羣體。

目前，公司正全力推進HLX43的臨牀開發進程，已在全球入組超過400例患者，並在中國、美國、日本、澳大利亞等多國順利推進患者入組。公司持續挖掘HLX43在多種實體瘤中的治療潛力，共計開設10項針對HLX43的臨牀研究，廣泛覆蓋非小細胞肺癌、胸腺癌、宮頸癌、肝細胞癌、食管鱗癌、頭頸鱗癌、鼻咽癌、結直腸癌、胃癌/胃食管交界部癌等。單藥之外，HLX43聯用其他產品的臨牀試驗也正在進行中，進一步探索「ADC+IO」的協同抗腫瘤療效。

未來，隨着HLX43在后線實體瘤患者中的療效逐步得到驗證，復宏漢霖也將持續將產品推向更前線的治療，加速為更多晚期/轉移性實體瘤患者帶來療效優異的新型治療選擇。

【參考文獻】

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

[2] 國際胸腺惡性腫瘤協作組織(ITMIG)關於胸腺瘤和胸腺癌的WHO組織學分類的共識

[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: . who.int/chapters/35.

[6] 中國醫師協會腫瘤多學科診療專業委員會. 中國胸腺上皮腫瘤臨牀診療指南(2021版) %J 中華腫瘤雜誌. 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

關於復宏漢霖

復宏漢霖（2696.HK）是一家國際化的創新生物製藥公司，致力於為全球患者提供可負擔的高品質生物藥，產品覆蓋腫瘤、自身免疫疾病、眼科疾病等領域，已在全球獲批上市9款產品，4個上市申請分別獲中國藥監局、美國FDA和歐盟EMA受理。自2010年成立以來，復宏漢霖已建成一體化生物製藥平臺，高效及創新的自主核心能力貫穿研發、生產及商業運營全產業鏈。公司已建立完善高效的全球創新中心，按照國際藥品生產質量管理規範（GMP）標準進行生產和質量管控，不斷夯實一體化綜合生產平臺，其中，公司商業化生產基地已相繼獲得中國、歐盟和美國GMP認證。

復宏漢霖前瞻性佈局了一個多元化、高質量的產品管線，涵蓋約50個分子，並全面推進基於自有抗PD-1單抗H藥漢斯狀的腫瘤免疫聯合療法。截至目前，公司已獲批上市產品包括全球首個獲批一線治療小細胞肺癌的抗PD-1單抗漢斯狀（斯魯利單抗，歐洲商品名：Hetronifly）、自主研發的中美歐三地獲批單抗生物類似藥漢曲優（曲妥珠單抗，美國商品名：HERCESSI，歐洲商品名：Zercepac）、國內首個生物類似藥漢利康（利妥昔單抗）、以及地舒單抗生物類似藥Bildyos和Bilprevda。公司亦同步就19個產品在全球範圍內開展30多項臨牀試驗，對外授權全面覆蓋歐美主流生物藥市場和眾多新興市場。

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.

(復星醫藥)