Denosumab biosimilar(Shanghai Henlius)

广谱抗肿瘤ADC：HLX43在免疫&化疗经治的NSCLC人群中展现疗效优势—≥4L的鳞状NSCLC患者中，ORR 达28.6%，其中多西他赛经治患者ORR为30%；≥3L的EGFR野生型非鳞状NSCLC患者中，ORR达46.7%，其中2.5mg/kg剂量组疗效更为显著，ORR达60% 不依赖生物标志物筛选：HLX43在各NSCLC亚组（有无EGFR突变、有无脑转移、PD-L1阳性/阴性）中都展现了优异的抗肿瘤疗效，其在晚期脑转移NSCLC患者中cORR达36.4%，DCR为100% “高效低毒”，安全性良好：HLX43相关的≥3级血液毒性发生率低，提示其扩展至1L治疗及联合治疗的潜力：常见≥3级TRAE包括贫血（19.6%）、白细胞计数降低（19.6%）等，其中血小板计数降低仅3.6%。此外，免疫相关不良事件（irAE）提示HLX43可通过免疫激活机制强化抗肿瘤疗效 2025年9月6日至9日，世界肺癌大会（World Conference on Lung Cancer, WCLC）在西班牙巴塞罗那举行。本次大会上，复宏汉霖创新型PD-L1 ADC HLX43治疗晚期/转移性实体瘤的临床I期更新数据入选口头报告和壁报导览两个环节。其中，西班牙时间9月6日上午11:00-11:06，在由国际肺癌研究协会（IASLC）、中国临床肿瘤学会（CSCO）和中国肺癌防治联盟（CAALC）共同举办的Joint IASLC-CSCO-CAALC Session联席会议上，复宏汉霖PD-L1 ADC HLX43的临床I期更新数据作为肺癌前沿研究的代表以口头报告的形式汇报。该研究的牵头主要研究者为中国医学科学院肿瘤医院王洁教授。 此次更新的数据进一步验证了HLX43在晚期非小细胞肺癌（NSCLC）等实体瘤中的卓越疗效，有望为标准治疗（免疫/化疗/靶向等）失败的后线耐药NSCLC患者带来更优的治疗方案，并作为一款广谱抗肿瘤基石药物，进一步拓展至肿瘤前线治疗及联合治疗方案。此前在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。 NSCLC疗效优势持续验证 EGFR野生型后线治疗潜力凸显 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，5年相对生存率较低[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，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高达50%的肺腺癌患者[3]。当前优异疗效产品仍较少，特别在2L+人等后线人群治疗上，仍然主要依赖于多西他赛为基础的化疗方案。因此，EGFR野生型NSCLC后线治疗仍是临床上亟待突破的难题之一[4,5]。 此次发布的更新研究数据来自一项开放标签、评估HLX43（抗 PD-L1 ADC）在晚期/转移性实体瘤患者中的安全性、药代动力学特征和初步疗效的首次人体 I 期临床研究（本次更新NSCLC人群数据）。研究包括Ia（剂量递增）的Ib期（剂量扩展）两个阶段。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NSCLC患者给与2mg/kg、2.5 mg/kg或3 mg/kg HLX43 (Q3W) 静脉注射，Ib期的主要终点为推荐的II期剂量（RP2D）和客观缓解率（ORR）。 本次更新的NSCLC患者数据来自Ia期+Ib期2.0 mg/kg剂量组及2.5 mg/kg剂量组。中位随访时间为9.0个月。 截至数据截止日期2025年6月28日，共计56例NSCLC患者入组Ia期及Ib期2.0和2.5 mg/kg剂量组，其中29例（51.8%）为鳞状，27例（48.2%）为非鳞状。鳞状NSCLC中，10例（34.5%）患者经多西他赛治疗失败。非鳞状NSCLC中，EGFR野生型/突变患者分别为15例（55.6%）及12例（44.4%）。 其中，非鳞状NSCLC患者为三线及以上后线人群（中位既往治疗线数：2），鳞状NSCLC患者为四线及以上后线人群（中位既往治疗线数：3）。54例（96.4%）患者接受过铂类药物治疗，50例（89.3%）患者和26例（46.4%）患者分别接受过免疫治疗和靶向治疗，14例患者（25%）接受过多西他赛治疗。 经研究者评估，54例可评估疗效患者的ORR为37.0%，疾病控制率（DCR）为87.0%。 亚组分析结果显示，在四线及以后的鳞状NSCLC患者（n=28）中，HLX43的ORR为28.6%，DCR为82.1%，较标准治疗药物多西他赛（ORR=12.8%）展现出显著的临床获益。值得关注的是，既往接受过多西他赛治疗的三线及后线NSCLC患者（n=10）ORR达30.0%，DCR为80%；接受2 mg/kg剂量HLX43治疗患者（n=15）ORR达40.0%，DCR为73.3%，提示HLX43在肺鳞癌后线治疗中的重要潜力。 在三线及以后的非鳞状NSCLC人群中（n=26），ORR达46.2%，DCR为96.2%。值得关注的是，EGFR野生型非鳞状NSCLC患者（n=15）的经确认客观缓解率（cORR）为46.7%，DCR达93.3%。接受2.5 mg/kg剂量HLX43治疗的患者（n=5）cORR高达60.0%，DCR为80%，彰显HLX43在非鳞状NSCLC患者人群中更为显著的疗效优势。 在晚期的脑转移NSCLC患者（n=11）中，HLX43仍带来了显著的治疗获益，cORR为36.4%，DCR达100.0%。 在PD-L1阴性（TPS＜1%，n=21）患者群体中，HLX43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。 安全性方面，最常见的≥3级治疗相关不良事件（TRAEs）为贫血（19.6%）、白细胞计数减少（19.6%）、中性粒细胞计数减少（16.1%）及淋巴细胞计数减少（12.5%），血小板计数减少仅3.6%。与此前在2025 ASCO上披露的安全性一致，HLX43血液学毒性较低，延续了良好的安全性，支持未来扩展至一线疗法及联合治疗方案。 其中，12例（21.4%）患者报告了免疫相关不良事件（irAE），8例（14.3%）患者出现免疫相关性肺病，多数为1-3级。 同时，在发生免疫相关性肺病的患者人群中观察到更高的治疗获益，包括50.0%的cORR 及100%的肿瘤缩小率，提示HLX43可能“双管齐下”，其疗效经由小分子毒素以及免疫机制介导。 潜在同类最优PD-L1 ADC 中美日澳全球开发进程全速推进 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显示出显著疗效，且耐受性良好。HLX43的I期临床数据显示其在NSCLC、胸腺鳞癌（TSCC）等实体瘤中展现出“高效、低毒”的治疗潜力，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患者人群都显示出优异疗效，不依赖生物标志物筛选。 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300例患者，并在中国、美国、日本等多国顺利推进患者入组。尤其在NSCLC适应症上，该国际多中心II期临床研究已累计获得中、美、日、澳等国家药监机构的临床许可，并在中、美两国完成首例受试者给药。同时，HLX43作为全球首个布局胸腺癌（TC）的PD-L1 ADC，已在美国等地获得该适应症的临床试验许可，计划于近期启动国际多中心临床研究，加速填补这一罕见高侵袭癌种ADC治疗的空白。 此外，复宏汉霖积极探索HLX43在多种实体瘤中的治疗潜力，包括宫颈癌、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，持续挖掘治疗潜力。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。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、靶向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。 【参考文献】 [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] Stanzione, B.; et al. Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor (EGFR) Common Mutations: New Strategies. Cancers 2025, 17, 1515. [4]中国临床肿瘤学会中国临床肿瘤学会(CSCO).(2024)非小细胞肺癌诊疗指南 [5] NCCN Guidelines Version 3. 2025, Non-Small Cell Lung Cancer. 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，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。 The Updated Clinical Results for PD-L1 ADC HLX43 at the 2025 WCLC, Demonstrate Outstanding Efficacy in NSCLC Broad Therapeutic Effects: HLX43 exhibits outstanding efficacy in IO & chemo treated NSCLC. The ORR was 28.6% for ≥4L squamous NSCLC patients, 30.0% for those who previously received docetaxel; cORR was 46.7% for EGFR wild-type non-squamous NSCLC, and 60.0% for those receiving HLX43 at 2.5 mg/kg Biomarker Independent: HLX43 demonstrates robust anti-tumor efficacy in various types of NSCLC (with or without EGFR mutation, with or without brain metastases, PD-L1 positive and negative). cORR was 36.4% and DCR was 100.0% for patients with brain metastasis Favorable Safety Profile：Low hematological toxicity (Grade ≥3 TRAEs) was observed for HLX43, supporting its potential for expansion into first-line setting and combination regimens. The most common grade ≥3 TRAEs include anemia (19.6%), white blood cell count decreased (19.6%), and platelet count decreased (3.6%). Immune-related AE (irAE) was reported, indicating HLX43 is capable of eliciting immunotherapeutic effects The 2025 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer (IASLC) was held from September 6-9 in Barcelona, Spain‌. Among the highlights is the updated results of the Phase 1 clinical trial of HLX43, Henlius’ PD-L1 ADC, which secured spots in both the oral presentation and poster tour session. During the Joint IASLC-CSCO-CAALC Session co-hosted by IASLC, the Chinese Society of Clinical Oncology (CSCO), and the China Lung Cancer Prevention and Treatment Alliance (CAALC), HLX43's updated phase 1 results were reported in the form of an oral presentation on September 6 (11:00 AM-11:06 AM). Professor Jie Wang from the Cancer Hospital of the Chinese Academy of Medical Sciences serves as the leading principal investigator(PI) of this study. The updated data further validated HLX43‘s outstanding efficacy in advanced/ metastatic solid tumors such as non-small cell lung cancer (NSCLC). It is poised to offer a superior treatment option for heavily treated NSCLC patients who have failed standard therapies (including immunotherapy, chemotherapy, targeted therapy, etc.) . Furthermore, with its broad-spectrum anti-tumor profile, HLX43 may serve as a cornerstone therapeutic agent, expanding into front-line treatment and combination therapy regimens. The results from the phase 1 clinical trial of HLX43 has been first released at the 2025 ASCO Annual Meeting. Sustained Efficacy in NSCLC, Highlights Potential for EGFR Wild-Type Later-Line Setting 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 diagnosed at advanced stages with a poor five-year survival prognosis [2], highlighting 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. 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]. The updated data released at the 2025 WCLC was from the open-label, first-in-human phase 1 clinical trial evaluating the safety, pharmacokinetics, and preliminary efficacy of HLX43 (Anti-PD-L1 ADC) in patients with advanced/metastatic solid tumors (with updated NSCLC cohort data). This study includes two parts. Phase 1a and 1b were a dose escalation and dose expansion phase, respectively. 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 1b were the recommended phase 2 (RP2D) dose and objective response rate (ORR). Here we present results in the NSCLC patients (from the phase 1a + phase 1b 2.0 and 2.5 mg/kg cohorts).  Median follow-up duration was 9.0 months. As of the data cut-off date Jun 28, 2025, a total of 56 (29 [51.8%] had squamous type and 27 [48.2%] had non-squamous) NSCLC patients were enrolled in phase 1a and phase 1b 2.0 and 2.5 mg/kg cohorts. In squamous population, 10 (34.5%) failed docetaxel treatment while in non-squamous NSCLC, 15 (51.8%) had a EGFR wild-type status and 12 (48.2%) had EGFR mutations. Among them, patients with non-squamous NSCLC were in the third-line or later setting (median prior lines of therapy: 2), while patients with squamous NSCLC were in the fourth-line or later setting (median prior lines of therapy: 3). Of all the patients, 54 (96.4%) had received platinum-based chemotherapy, 50 (89.3%) had received immunotherapy, 26 (46.4%) had received targeted therapy, and 14 (25.0%) had been treated with docetaxel. Investigator-assessed ORR in the 54 response-evaluable patients was 37.0%, with a disease control rate (DCR) of 87.0%. Subgroup analysis showed that in heavily pre-treated patients with squamous NSCLC (fourth-line or later, n=28), HLX43 conferred an ORR of 28.6% and a DCR of 82.1%, representing a significant clinical benefit compared to standard therapy docetaxel (ORR=12.8%). Notably, in patients who had received prior docetaxel treatment (n=10), the ORR reached 30.0% with a DCR of 80.0%. Furthermore, among these patients who receive HLX43 at the 2 mg/kg dose (n=15), ORR was 40.0% with a DCR of 73.3%, underscoring its potent therapeutic potential in heavily treated squamous NSCLC. ORR was 46.2%, with a DCR of 96.2% in the third-line or later non-squamous NSCLC population (n=26). Notably, confirmed ORR (cORR) was 46.7% for patients with an EGFR wild-type non-squamous NSCLC (n=15). Among these patients, cORR was 60.0% for those receiving HLX43 at 2.5 mg/kg (n=5)，highlighting superior efficacy of HLX43 in the non-squamous NSCLC subgroup. In advanced NSCLC patients with brain metastasis (n=11), HLX43 still delivered significant clinical benefits, with a cORR of 36.4% and DCR of 100.0%. Moreover, HLX43 exhibits rubust efficacy in PD-L1 negative (TPS <1%, n=21) patients,  with a ORR of 38.1% and DCR of 85.7%, indicating its differented therapeutic potential to cover a broader patient population regardless of PD-L1 expression. In terms of safety and tolerability, the most common grade ≥3 TRAEs were anemia (19.6%), white blood cell count decreased (19.6%), neutrophil count decreased (16.1%), and lymphocyte count decreased (12.5%). Platelet count decreased was reported in 3.6% of all treated patients. Building onto the favorable safety profile previously disclosed at the 2025 ASCO annual meeting, HLX43 continued to demonstrate low hematological toxicity, supporting its potential for expansion into first-line setting and combination therapies. Immune-related AE was reported in 12 (21.4%) patients. Immune-mediated lung disease was reported in 8 (14.3%) patients, most of which were grade 1-3. In these patients with immune-mediated lung disease, the cORR was 50.0% and 100% tumor shrinkage was observed, highlighting the immunotherapeutic effects of HLX43 in addition to its payload-mediated cytotoxic tumor cell killing. Potential Best-in-class PD-L1 ADC, Advances Global Development in China, the U.S., Japan, and Australia etc. Key Markets 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 non-small cell lung cancer (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. Currently, Henlius is advancing the clinical development of HLX43 at full speed, with over 300 patients enrolled globally and patient recruitment progressing smoothly in multiple countries including China, the U.S., and Japan. For NSCLC, HLX43 has already been approved to conduct phase 2 MRCT in China, the U.S., Japan and Australia, with first patients successfully dosed in both China and the U.S. Simultaneously, as the world's first PD-L1 ADC indicated for thymic carcinoma (TC), HLX43 has received clinical trial approvals for the indication in the U.S. and other regions. A MRCT is planned to be initiated, aiming to fill the therapeutic gap in ADC treatment for this aggressive cancer type. In addition, the company is also accelerating the phase 2 clinical development of HLX43 in various solid tumors, including 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/gastroesophageal junction cancer (GC/GEJC). Both monotherapy and combination therapies of HLX43 with other products 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. Reference [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] Stanzione, B.; et al. Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor (EGFR) Common Mutations: New Strategies. Cancers 2025, 17, 1515. [4]中国临床肿瘤学会中国临床肿瘤学会(CSCO).(2024)非小细胞肺癌诊疗指南 [5] NCCN Guidelines Version 3. 2025, Non-Small Cell Lung Cancer. 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, 9 products have been approved for marketing worldwide, 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 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. 联系方式 媒体：PR@Henlius.com 投资者：IR@Henlius.com 喜欢本文内容 点击下方按钮·分享 ·收藏 ·点赞 ·在看