摘要：2025年6月3日，复星医药子公司复宏汉霖（2696.HK）宣布，公司在2025美国临床肿瘤学会（ASCO）年会上首次公布了HLX43（PD-L1 ADC）治疗晚期/转移性实体瘤患者的I期临床试验数据，该研究由中国医学科学院肿瘤医院王洁教授担任牵头主要研究者。

转自：复星医药

2025年6月3日，复星医药子公司复宏汉霖（2696.HK）宣布，公司在2025美国临床肿瘤学会（ASCO）年会上首次公布了HLX43（PD-L1 ADC）治疗晚期/转移性实体瘤患者的I期临床试验数据，该研究由中国医学科学院肿瘤医院王洁教授担任牵头主要研究者。凭借精准的分子设计和多重创新机制，HLX43在晚期/转移性实体瘤患者中显示出优异的抗肿瘤活性和可控的安全性，尤其在非小细胞肺癌（NSCLC）和胸腺鳞状细胞癌（TSCC）患者人群中展现了令人鼓舞的初步疗效，具备同类最优产品的开发潜力。目前，全球范围内尚无PD-L1 ADC获批上市，HLX43有望解决PD-1/L1免疫疗法不响应或耐药问题，为更多晚期/转移性实体瘤患者带来新的治疗选择。

I期临床数据首次发布：

令人鼓舞的安全性和初步疗效，

NSCLC及TSCC适应症数据亮眼

此次在ASCO 发布的研究数据来自一项评估 HLX43（抗 PD-L1 ADC）在晚期/转移性实体瘤患者中的安全性、耐受性和药代动力学特征的 I 期临床研究。研究结果显示，HLX43在不同剂量下耐受性良好，未出现新的安全性信号，并在接受标准治疗失败的晚期实体瘤患者（包括非小细胞肺癌患者、胸腺鳞癌患者）中表现出令人鼓舞的初步有效性，值得进一步研究。

本I期研究由两个阶段组成，Ia期和Ib期分别为剂量递增阶段和剂量扩增阶段，旨在探索HLX43的不同剂量特征。在Ia期中，组织学或细胞学确诊为晚期/转移性恶性实体瘤且对标准治疗无效或无法接受标准治疗的患者接受每三周一次（Q3W）0.5 mg/kg、1 mg/kg、2 mg/kg、2.5 mg/kg、3 mg/kg或4 mg/kg HLX43静脉注射。在Ib期中，对标准治疗无效的晚期/转移性非小细胞肺癌（NSCLC）患者接受 2mg/kg、2.5 mg/kg或3 mg/kg HLX43 (Q3W) 静脉注射。Ia期的主要终点是每个剂量组中首次给药后三周内经历剂量限制毒性（DLT）的受试者比例以及最大耐受剂量（MTD），而Ib期的主要终点是推荐的II期剂量（RP2D）和BICR评估的客观缓解率（ORR）。

截至数据截止日期2025年3月28日，共有21名患者纳入到Ia阶段，接受剂量为0.5 mg/kg (n=3)、1 mg/kg (n=3)、2 mg/kg (n=3)、2.5 mg/kg (n=3)、3 mg/kg (n=3)或4 mg/kg (n=6)的HLX43治疗。鉴于2.5和3.0 mg/kg剂量组的患者招募仍在进行中,关于Ib期，这里仅展示2.0 mg/kg组数据。Ib期2 mg/kg组共入组21名非小细胞肺癌（NSCLC）患者（其中15名[71.4%]为鳞状，6名[28.6%]为非鳞状）。Ia期和Ib期2.0 mg/kg组的中位随访时间分别为9.7个月和7.0个月。Ia及Ib期患者的既往中位治疗线数（Median Prior lines）分别为2和3。Ib 期患者之前均接受过铂类药物治疗。

研究者评估的Ia期的客观缓解率（ORR）为36.8%；75%的胸腺鳞状细胞癌患者达到部分缓解（3/4名，ORR = 75%）。Ib期2.0 mg/kg组NSCLC患者经研究者评估的ORR为38.1%，其中鳞状NSCLC患者的ORR为40%。值得关注的是，脑转移NSCLC患者的疾病控制率（DCR）达到100%。

Ia期研究的中位无进展生存期（PFS）为4.2个月，Ib期2.0 mg/kg组的中位PFS为5.4个月。中位总生存期（OS）分别为8.9个月和未达到。

所有的患者均报告有治疗期间出现的不良事件（TEAEs），大多为1-2级。Ia和Ib期研究中，3级或以上的治疗相关不良事件（TRAE）发生率分别为28.6%（Ia）和42.9%（Ib,2.0mg/kg）。2.0 mg/kg剂量下HLX43血液学毒性较低（贫血14.3%，淋巴细胞下降14.3%，血小板下降0%，中性粒细胞下降0%），支持未来扩展至一线疗法及联合治疗方案。

广谱抗肿瘤ADC ，

多重创新机制有望惠及全人群患者

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。临床前研究显示，HLX43具有显著的抗肿瘤疗效，且具有良好的安全性。

作为全球率先进入临床阶段的靶向PD-L1的ADC产品，HLX43于2023年相继获得中国药品监督管理局（NMPA）、美国食品药品监督管理局（FDA）的临床试验许可，目前已进入II期临床开发阶段，广泛覆盖非小细胞肺癌、胸腺鳞癌、肝细胞癌、食管鳞癌、头颈鳞癌、宫颈癌、鼻咽癌等实体瘤的治疗。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。

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，已有6款产品在中国获批上市，4款产品在国际获批上市，5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国内首个生物类似药汉利康®（利妥昔单抗）、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®）、汉达远®（阿达木单抗）、汉贝泰®（贝伐珠单抗）、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®）以及汉奈佳®（奈拉替尼）。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。

Results from the Phase 1 Clinical Trial of Henlius PD-L1 ADC HLX43 Released at 2025 ASCO Annual Meeting

Shanghai, China, June, 3, 2025 – Shanghai Henlius Biotech, Inc. (2696. HK) announced the first release of results from the phase 1 clinical trial of HLX43, a PD-L1-targeting antibody-drug conjugate (ADC), for the treatment of advanced or metastatic solid tumors at the 2025 ASCO Annual Meeting. The leading principal investigator of this study is Jie Wang from the Cancer Hospital Chinese Academy of Medical Sciences. Leveraging on the precise molecular design and multiple innovative mechanisms, HLX43 has demonstrated superior anti-tumor activity with a manageable safety profile in patients with advanced/metastatic solid tumors. Particularly, encouraging preliminary efficacy was observed in non-small cell lung cancer (NSCLC) and thymic squamous cell carcinoma (TSCC) patients, demonstrating best-in-class potential for clinical development. At present, no PD-L1 targeting ADC has been approved for marketing globally. HLX43 may thus 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.

Initial Phase 1 Data Presentation: Favorable Safety Profile and Preliminary Antitumor Activity Observed, Especially in the NSCLC and TSCC Paients

The results presented at the 2025 ASCO Annual Meeting were from the phase 1 clinical study, which evaluated the safety, tolerability, and pharmacokinetic characteristics of HLX43 (Anti-PD-L1 ADC) in patients with advanced/metastatic solid tumors. The results indicated that HLX43 was well tolerated with no new safety signals across different dose and exhibited encouraging preliminary efficacy in patients with advanced solid tumors, including those with NSCLC and TSCC, who had failed standard therapies, which warrants further investigation.

Study Design:

This study includes two parts. Phase 1a and 1b were a dose escalation and dose expansion phase, respectively, to explore different doses of HLX43. In phase 1a, patients with histologically or cytologically confirmed advanced/metastatic malignant solid tumors that were refractory to or could not receive standard therapies received intravenous HLX43 at 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 2.5 mg/kg, 3 mg/kg, or 4 mg/kg, Q3W. In phase 1b, patients with advanced/metastatic non-small cell lung cancer (NSCLC) refractory to standard treatment received HLX43 at 2 mg/kg, 2.5 mg/kg, or 3 mg/kg, Q3W. The primary endpoints for phase 1a were the proportion of subjects experiencing dose-limiting toxicity (DLT) in each dose group within three weeks after the first administration of HLX43 and the maximum tolerable dose (MTD) while that for phase 1b were the recommended phase 2 (RP2D) dose and BICR-assessed objective response rate (ORR).

Results:

As of the data cut-off date Mar 28, 2025, a total of 21 patients were enrolled in phase 1a to receive HLX43 at 0.5 mg/kg (n=3), 1 mg/kg (n=3), 2 mg/kg (n=3), 2.5 mg/kg (n=3), 3 mg/kg (n=3), or 4 mg/kg (n=6). In phase 1b, 21 patients with NSCLC (15 [71.4%] had squamous type and 6 [28.6%] had nonsquamous) were enrolled to receive HLX43 at 2 mg/kg; enrolment of patients into the 2.5 and 3.0 mg/kg dose groups is ongoing. Hence, only the data from the 2.0 mg/kg group is presented here. Median follow-up duration was 9.7 months and 7.0 months for the two respective cohorts. The median prior lines of therapy for phase 1a and 1b patients were 2 and 3 respectively. All patients in phase 1b 2.0 mg/kg group received platinum-based treatment previously.

Investigator-assessed ORR for the phase 1a cohorts was 36.8%; 75% patients with thymic squamous cell carcinoma achieved partial response (ORR = 75%, 3/4). Investigator-evaluated ORR for the phase 1b 2.0 mg/kg cohort was 38.1%. ORR in the squamous NSCLC patients was 40%. Notably, the disease control rate (DCR) in NSCLC patients with brain metastasis reached 100%.

Median progression-free survival (PFS) was 4.2 months for the phase 1a cohorts and 5.4 months for phase 1b 2.0 mg/kg cohort. Median overall survival (OS) was 8.9 months and not reached, respectively.

All patients in the various dose groups experienced treatment-emergent adverse events (TEAEs) that were mostly grades 1-2. In phase 1a and 1b, the incidence rates of grade 3 or higher treatment-related adverse events (TRAEs) were 28.6% (n=21) and 42.9% (n=21), respectively. At 2.0 mg/kg dose level, HLX43 demonstrated low hematologic toxicity (anemia 14.3%, lymocyte count decreased 14.3%, platelet count decreased 0%, neutrophil count decreased 0%), supporting future expansion into 1L therapy and combination regimens.

Pan-Tumor Targeting ADC with Innovative Mechanisms of Action to Benefit Broad-spectrum Tumor Patients

HLX43 is a novel PD-L1-targeting 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 PD-L1-expressing tumor cells, HLX43's cytotoxic payload can be delivered into tumor cells via dual mechanisms—First, the ADC undergoes 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 antitumor efficacy. Preclinical and phase 1 studies have demonstrated that, HLX43 has a favorable safety profile and exhibits potent anti-tumor activity.

HLX43 is the leading PD-L1-targeting ADCs that is progressing to clinical development globally. It has received investigational new drug (IND) approvals from the China National Medical Products Administration (NMPA) and the U.S. Food and Drug Administration (FDA). Currently, HLX43 is being investigated in phase 2 clinical trials for a variety of solid tumor indications including NSCLC, TSCC, HCC, ESCC, HNSCC, CC and NPC. Both monotherapy studies and a phase 1b/2 trial combining HLX43 with serplulimab (HANSIZHUANG, 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.

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.

来源：新浪财经