复宏汉霖HLX43获多国批准开展NSCLC国际多中心II期临床，引领 PD-L1 ADC全球开发进程

据GLOBOCAN最新数据显示，肺癌是全球发病率和死亡率最高的癌症，2022年全球约有超过248万新发肺癌病例，占癌症新发病例的12.4%^[1]，其中非小细胞肺癌（NSCLC）是最常见的肺癌类型（约85%）。大部分肺癌患者确诊时已处于疾病晚期阶段^[2]，存在巨大的尚未满足的临床需求。根据病理类型，NSCLC又可分为鳞状细胞癌（约30%）、肺腺癌（约50%）等，尽管针对EGFR等驱动基因突变（AGA）的靶向治疗方案已经趋于成熟，但在全部NSCLC患者中，EGFR野生型占比高达70%-85%，涵盖几乎所有的鳞癌患者和50-55%的肺腺癌患者^[3]。当前疗效优异的产品仍较少，特别在2L+人等后线人群治疗上，仍主要依赖于多西他赛为基础的化疗方案，后线治疗的效果有限^[4,5]。

HLX43是一款靶向程序性死亡-配体1（PD-L1）的新型ADC候选药物，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。HLX43兼具毒素精准杀伤和肿瘤免疫作用的复合功能：其毒素不仅能够藉靶点内吞进入肿瘤细胞后进行释放，并在肿瘤微环境中释放后借助旁观者效应进入肿瘤细胞，阻断DNA复制，从而导致肿瘤细胞凋亡；此外，HLX43的PD-L1靶向抗体可激活免疫调节机制，发挥协同抗肿瘤效应。

在2025 美国临床肿瘤学会（ASCO）年会上，HLX43的I期临床数据首次发布，展现出令人鼓舞的初步疗效和安全性，对鳞状/非鳞状NSCLC，有无EGFR突变、有无脑/肝转移、PD-L1阳性/阴性的NSCLC患者都展现了优异的治疗潜力。研究显示，2.0 mg/kg每三周输注一次HLX43时，晚期NSCLC患者经研究者评估的ORR为38.1%，对于四线及更后线治疗的难治NSCLC患者，ORR仍可达38.5%。 其中鳞状非小细胞肺癌sqNSCLC（n=15）和非鳞状非小细胞肺癌nsqNSCLC（n=6）患者的客观缓解率（ORR）分别为40%和33.3%，并实现了73.3%和100%的疾病控制。值得关注的是，脑转移NSCLC患者全部得到疾病控制（DCR=100%）。除NSCLC外，HLX43在胸腺鳞状细胞癌（TSCC）患者人群中疗效显著，ORR达75%（3/4名）。

目前公司正在全力推进HLX43临床开发进程，积极探索其在多种实体瘤中的治疗潜力，包括非小细胞肺癌、胸腺鳞癌、肝细胞癌、食管鳞癌、头颈鳞癌、宫颈癌、鼻咽癌等。单药之外，HLX43联用复宏汉霖自研斯鲁利单抗（H药汉斯状^®，抗PD-1单抗）治疗实体瘤的 Ib/II 期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。HLX43不仅可能克服PD-1/L1免疫疗法不响应或耐药问题，并对化疗、TKI治疗失败的患者都具有潜在疗效，有望为更多晚期/转移性实体瘤患者带来新的治疗选择。

未来，复宏汉霖将加速推动HLX43在全球范围内的研发进程，不断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、可负担的创新治疗方案。

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.

媒体：PR@Henlius.com

投资者：IR@Henlius.com