全球研發 | 復星醫藥子公司復宏漢霖HLX43獲多國批准開展NSCLC國際多中心...

近日，復星醫藥子公司復宏漢霖創新型程序性死亡-配體1（PD-L1）抗體偶聯藥物（ADC）注射用HLX43全球開發再度取得重要進展，該產品已獲得中國國家藥品監督管理局（NMPA）、美國食品藥品監督管理局（FDA）、澳大利亞藥品管理局（TGA）及日本藥品醫療器械綜合機構（PMDA）許可，開展針對晚期非小細胞肺癌（NSCLC）的國際多中心II期臨牀研究，並於此前在中國境內完成首例受試者給藥。全球尚無同類靶向PD-L1的ADC產品獲批上市，HLX43為全球首個進入臨牀II期的PD-L1 ADC。

據GLOBOCAN最新數據顯示，肺癌是全球發病率和死亡率最高的癌症，2022年全球約有超過248萬新發肺癌病例，佔癌症新發病例的12.4%^[1]，其中非小細胞肺癌（NSCLC）是最常見的肺癌類型（約85%）。大部分肺癌患者確診時已處於疾病晚期階段^[2]，存在巨大的尚未滿足的臨牀需求。根據病理類型，NSCLC又可分為鱗狀細胞癌（約30%）、肺腺癌（約50%）等，儘管針對EGFR等驅動基因突變（AGA）的靶向治療方案已經趨於成熟，但在全部NSCLC患者中，EGFR野生型佔比高達70%-85%，涵蓋幾乎所有的鱗癌患者和50-55%的肺腺癌患者^[3]。當前療效優異的產品仍較少，特別在2L+人等后線人羣治療上，仍主要依賴於多西他賽為基礎的化療方案，后線治療的效果有限^[4,5]。

HLX43是一款靶向程序性死亡-配體1（PD-L1）的新型ADC候選藥物，由全人源IgG1抗PD-L1抗體與創新連接子-拓撲異構酶抑制劑荷載偶聯而成，藥物抗體比（drug-to-antibody ratio, DAR）約為8。HLX43兼具毒素精準殺傷和腫瘤免疫作用的複合功能：其毒素不僅能夠藉靶點內吞進入腫瘤細胞后進行釋放，並在腫瘤微環境中釋放后藉助旁觀者效應進入腫瘤細胞，阻斷DNA複製，從而導致腫瘤細胞凋亡；此外，HLX43的PD-L1靶向抗體可激活免疫調節機制，發揮協同抗腫瘤效應。

在2025 美國臨牀腫瘤學會（ASCO）年會上，HLX43的I期臨牀數據首次發佈，展現出令人鼓舞的初步療效和安全性，對鱗狀/非鱗狀NSCLC，有無EGFR突變、有無腦/肝轉移、PD-L1陽性/陰性的NSCLC患者都展現了優異的治療潛力。研究顯示，2.0 mg/kg每三周輸注一次HLX43時，晚期NSCLC患者經研究者評估的ORR為38.1%，對於四線及更后線治療的難治NSCLC患者，ORR仍可達38.5%。 其中鱗狀非小細胞肺癌sqNSCLC（n=15）和非鱗狀非小細胞肺癌nsqNSCLC（n=6）患者的客觀緩解率（ORR）分別為40%和33.3%，並實現了73.3%和100%的疾病控制。值得關注的是，腦轉移NSCLC患者全部得到疾病控制（DCR=100%）。除NSCLC外，HLX43在胸腺鱗狀細胞癌（TSCC）患者人羣中療效顯著，ORR達75%（3/4名）。

目前公司正在全力推進HLX43臨牀開發進程，積極探索其在多種實體瘤中的治療潛力，包括非小細胞肺癌、胸腺鱗癌、肝細胞癌、食管鱗癌、頭頸鱗癌、宮頸癌、鼻咽癌等。單藥之外，HLX43聯用復宏漢霖自研斯魯利單抗（H藥漢斯狀，抗PD-1單抗）治療實體瘤的 Ib/II 期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。HLX43不僅可能克服PD-1/L1免疫療法不響應或耐藥問題，並對化療、TKI治療失敗的患者都具有潛在療效，有望為更多晚期/轉移性實體瘤患者帶來新的治療選擇。

未來，復宏漢霖將加速推動HLX43在全球範圍內的研發進程，不斷夯實更多創新分子的差異化佈局，為更多腫瘤患者帶來高質量、可負擔的創新治療方案。

參考文獻

[1] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263.

[2] Robinson CG, et al. Postoperative Radiotherapy for Pathologic N2 Non–Small-Cell Lung Cancer Treated with Adjuvant Chemotherapy: A Review of the National Cancer Data Base. Journal of Clinical Oncology 2015, 33(8): 870-876.

[3] Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res. 2015 Feb;4(1):36-54. 

[4] 中國臨牀腫瘤學會 中國臨牀腫瘤學會(CSCO).(2024)非小細胞肺癌診療指南

[5] NCCN Guidelines Version 3. 2025, Non-Small Cell Lung Cancer.

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，已有6款產品在中國獲批上市，4款產品在國際獲批上市，5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國內首個生物類似藥漢利康（利妥昔單抗）、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）、漢達遠（阿達木單抗）、漢貝泰（貝伐珠單抗）、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）以及漢奈佳（奈拉替尼）。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 Global Regulatory Approvals for Phase 2 MRCT of Its PD-L1 ADC HLX43 on NSCLC 

Recently, Henlius has achieved significant advancement in the global development of HLX43, its innovative programmed death-ligand 1 (PD-L1) targeting antibody-drug conjugate (ADC), which has already been approved by the China National Medical Products Administration (NMPA), the U.S. Food and Drug Administration (FDA), Australia Therapeutic Goods Administration (TGA) and Japan's Pharmaceuticals and Medical Devices Agency (PMDA) to initiate phase 2 multi-regional clinical trial in patients with advanced non-small cell lung cancer (NSCLC). Additionally, the first patient dosing has been completed in China. To date, no PD-L1 targeting ADC has been approved for marketing globally. HLX43 is the first PD-L1 ADC progressed to phase 2 clinical trial development globally.

Lung cancer is the most common cancer worldwide in terms of incidence and mortality. According to GLOBOCAN 2022, there were over 2.48 million new cases of lung cancer globally in 2022, accounting for 12.4% of all new cancer cases ^[1]. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (approximately 85%).The majority of lung cancer patients are are diagnosed at advanced stages ^[2], indicating a significant unmet clinical need. By histology, NSCLC can be classified into squamous cell carcinoma (approximately 30%), adenocarcinoma (approximately 50%) and other subtypes including large cell carcinoma.  While targeted therapies for driver gene mutations, such as EGFR, have become well-established, EGFR wild-type cases account for 70%-85% of all NSCLC patients, including nearly all squamous cell carcinoma cases and 50-55% of adenocarcinoma cases ^[3]. Currently, the treatment landscape of EGFR wild-type NSCLC remains limited by a scarcity of highly effective options, particularly in second-line and later (2L+) therapy, where docetaxel-based chemotherapy continues to serve as the standard of care despite its suboptimal efficacy ^[4,5].

HLX43 is a novel PD-L1 directed ADC, 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. Its mechanisms of action integrate targeted cytotoxic delivery and immune checkpoint activation through PD-L1/PD-1 blockade. Upon binding to tumor cells with PD-L1 expression, the cytotoxic payload of HLX43 will be delivered into tumor cells via dual mechanisms. HLX43 will undergo receptor-mediated endocytosis, releasing the cytotoxic payload intracellularly via linker cleavage, and the payload further diffuses into neighboring tumor cells via bystander effect, thereby blocking DNA replication and triggering tumor cell apoptosis. Meanwhile, the anti-PD-L1 antibody of HLX43 activates immune modulation and blocks immune checkpoints, driving synergistic anti-tumor efficacy.

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. Investigator-evaluated ORR for the phase 1b 2.0 mg/kg cohort was 38.1%, and ORR reached 38.5% in heavily pre-treated NSCLC patients (≥4L). ORRs in the sqNSCLC (n=15) and nsqNSCLC (n=6) patients reached 40% and 33.3%, with 73.3% and 100% for the DCRs of the two subgroups of patients, respectively. Notably, the DCR in NSCLC patients with brain metastasis reached 100%. In addition, 75% patients with thymic squamous cell carcinoma (TSCC) achieved partial response (ORR=75%, 3/4).

The company is currently accelerating the clinical development of HLX43 and actively exploring its therapeutic potential in various solid tumors, including NSCLC, TSCC, hepatocellular carcinoma (HCC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC), cervical cancer (CC) and nasopharyngeal cancer (NPC). Both monotherapy studies and a phase 1b/2 trial combining HLX43 with serplulimab (Henlius' proprietary anti-PD-1 monoclonal antibody) are ongoing simultaneously to further exploit the synergistic effects of ADC-mediated cytotoxicity and immunotherapy-induced immune activation. HLX43 may benefit more patients with advanced or metastatic solid tumors by providing a novel treatment option for those who are unresponsive or have developed resistance to PD-1/PD-L1-targeted therapies, as well as the patients who have failed prior chemotherapy or TKI therapies.

Looking forward, Henlius will accelerate the global development of HLX43, continuously strengthening the differentiated layout of more innovative molecules to bring high-quality, affordable innovative treatment options 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. Up to date, 6 products have been launched in China, 4 have been approved for marketing in overseas markets, and 5 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 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), HANSIZHUANG (serplulimab, trade name: Hetronifly in Europe), the world’s first anti-PD-1 mAb for the first-line treatment of SCLC, and HANNAIJIA (neratinib). 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)