创新加速度 | 复宏汉霖新一代靶向CD47-SIRPα融合蛋白HLX701完成晚期结直肠癌Ib/II期首例患者给药

2026年3月26日，复宏汉霖（2696.HK）宣布，公司创新型重组人SIRPα-Fc融合蛋白注射液HLX701联合西妥昔单抗及化疗治疗晚期RAS/BRAF野生型结直肠癌患者的Ib/II期临床研究（HLX701-CRC201）完成首例患者给药。

结直肠癌是我国乃至全球高发的恶性肿瘤。2022年，全球新发结直肠癌约192.6万例，死亡约90.4万例，其中我国新发及死亡病例分别达51.7和24.0万例，位居恶性肿瘤发病率的第二位，死亡率的第四位^1-2。对于晚期/转移性结直肠癌，一、二线标准治疗方案主要为基于氟尿嘧啶类的化疗药物联合抗血管生成药物（抗VEGF靶向治疗）或抗EGFR靶向治疗。其中，西妥昔单抗（抗EGFR单抗）联合化疗是RAS/BRAF野生型晚期结直肠癌的标准一线治疗方案之一。随着疾病进展，后线治疗选择有限且获益仍有待提升，目前可选方案包括瑞戈非尼、呋喹替尼、TAS-102等^3-7，临床亟需更有效、可联合的治疗策略。靶向CD47-SIRPα信号通路的免疫治疗已在结直肠癌等实体瘤和血液瘤中展开了初步临床探索，尤其联合治疗在肿瘤特定分子分型中显示出协同治疗潜力^8-9。随着新一代CD47-SIRPα靶向药物的持续升级和迭代，其疗效及联合策略亟待在临床研究中进一步验证。

HLX701是复宏汉霖自汉康生技（HanchorBio）旗下FBD Biologics Limited（简称“FBD”）引进，并由双方依据合作协议共同推进开发的新一代SIRPα-Fc融合蛋白。该分子是一种工程改造的人类SIRPα免疫球蛋白（IgV）结构域与人免疫球蛋白G4（IgG4）片段可结晶（Fc）区域蛋白结合的融合蛋白，能够以高亲和力结合肿瘤细胞上的CD47，有效阻断抑制性CD47“别吃我”抗吞噬信号，从而促进巨噬细胞对肿瘤细胞的吞噬作用及增强抗肿瘤活性，并通过抗原呈递激活T细胞、辨识抗原，最终实现先天免疫与适应性免疫的系统性协同。

值得关注的是，临床前和早期临床研究显示，HLX701在选择性结合肿瘤CD47的同时，与红细胞（RBC）等正常细胞上的CD47结合亲和力较低，且不引起RBC凝集、不诱导巨噬细胞吞噬RBC, 因而HLX701在临床上引发贫血和血小板减少等常见副作用的可能性较低。临床前研究显示，HLX701联合化疗、免疫检查点抑制剂、表皮生长因子受体抑制剂及抗血管生成药物等在结直肠癌、胃癌、乳腺癌、肺癌等动物模型中皆可产生协同抗肿瘤疗效。目前，HLX701单药剂量递增的I期临床研究正在中美同步开展，其联合不同药物的剂量递增及剂量扩展的Ib/IIa期临床研究也已在中国启动。

复宏汉霖深耕肿瘤免疫治疗领域，已前瞻性布局了包括H药汉斯状^®（斯鲁利单抗）、抗PD-L1 ADC HLX43 等多款具有广谱治疗潜力的创新分子。目前，H药作为全球首个获批一线治疗小细胞肺癌（SCLC）的抗PD-1单抗，同时是全球首个且唯一胃癌围手术期III期注册研究成功的抗PD-1单抗，已在中国、德国、英国、印度、新加坡等40多个国家和地区获批上市。HLX43为潜在同类最优（best-in-class）的创新型PD-L1 ADC，兼具免疫检查点阻断（IO）与载荷细胞毒性（ADC）的双重疗效，在非小细胞肺癌（NSCLC）、宫颈癌、食管鳞癌等实体瘤中展现出令人鼓舞的安全性和初步疗效，并在更多实体瘤中陆续验证。作为复宏汉霖肿瘤免疫管线的重要组成，HLX701差异化的分子设计有望带来更好的安全性特征，与复宏汉霖现有管线形成深度协同，为新一代肿瘤免疫治疗方案开辟路径。

未来，复宏汉霖将持续聚焦未满足的临床需求，立足于公司在抗体领域的累积优势，不断扩充创新潜力靶点，积极探索前沿技术与疗法，加强优质创新资产的合作，为全球患者带来更多高质量、可负担的创新治疗方案。

关于HLX701-CRC201

本研究为一项在既往接受过化疗的复发性、不可切除或转移性RAS/BRAF野生型结直肠癌患者中，比较HLX701联合西妥昔单抗和化疗（FOLFOX/FOLFIRI）对比安慰剂联合西妥昔单抗和化疗（FOLFOX/FOLFIRI）的1b/2期临床研究。该研究包括三个阶段：第一阶段为安全导入期，采用 3+3 剂量递增设计，设5 mg/kg至18mg/kg共4个剂量组，受试者将接受不同剂量的HLX701联合西妥昔单抗和化疗（FOLFOX/FOLFIRI）进行治疗，每周一次静脉给药；第二阶段为剂量扩展期，设8 mg/kg至18 mg/kg 共3个剂量组，每周一次静脉给药，旨在评价不同剂量水平HLX701联合西妥昔单抗和化疗（FOLFOX/FOLFIRI）的临床疗效和安全性；第三阶段为随机、双盲、多中心研究，对比HLX701或安慰剂联合西妥昔单抗和化疗的疗效和安全性。

本研究第一阶段的主要终点为评估剂量限制毒性（DLT）的发生比例，次要终点为不良事件等安全性指标、客观缓解率（ORR）和疾病控制率（DCR）等疗效指标、PK参数、免疫原性等；第二阶段主要终点为探索2期推荐剂量（RP2D）、独立影像评估委员会（BICR）评估的ORR和无进展生存期（PFS）；第三阶段主要终点为BICR评估的ORR、PFS；第二和第三阶段的次要终点包括不良事件等安全性指标、总生存期（OS）、研究者评估的ORR、PFS等疗效指标、PK参数和免疫原性等，同时将探索生物标志物与疗效的相关性。

关于复宏汉霖

复宏汉霖（2696.HK）是一家国际化创新生物制药企业，致力于为全球患者提供高品质、可负担的生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域。自2010年成立以来，公司已构建涵盖全球研发、临床、注册、生产及商业化的全产业链平台，拥有全球员工近4,000人，并在中国、美国和日本等多地设有运营及分支机构。依托生物类似药形成的稳健现金流反哺创新研发，复宏汉霖正稳步迈入“全球化2.0”阶段，持续打造可复制、可持续的全球增长模式。截至2026年初，公司共有10款产品在全球60个国家和地区获批上市，其中7款已在中国获批。在欧美主流生物药市场，复宏汉霖亦取得多项里程碑式突破，已有4款产品获得美国FDA批准、4款产品获得欧盟EC批准，充分体现了公司在研发体系、质量管理及生产能力方面已全面对标国际最高标准。

在创新驱动方面，复宏汉霖依托上海、美国等多地协同布局的研发体系，构建了多元化、平台化的创新技术矩阵，覆盖免疫检查点抑制剂、免疫细胞衔接器（包括多特异性TCE）、抗体偶联药物（ADC）以及AI驱动的早期研发平台等前沿方向。目前，公司拥有50余项处于早期阶段的创新资产，其中约70%具备同类最佳（Best-in-Class）潜力，并在全球同步推进30余项临床研究。核心产品H药汉斯状^®（斯鲁利单抗，欧洲商品名：Hetronifly^®）作为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗，正加速全球布局，已在全球40余个市场获批上市；同时，多款潜力创新资产，包括PD-L1 ADC HLX43及新表位HER2单抗HLX22正全面推进全球关键性临床研究。依托通过中、欧、美三地GMP认证的生产体系，复宏汉霖已建成总产能达84,000升的生物药生产平台，形成覆盖全球六大洲的稳定供应网络。未来，复宏汉霖将始终坚持以患者为中心，聚焦未满足的临床需求，持续推动创新成果向临床价值与患者可及转化，在全球生物医药创新生态中创造长期而稳健的价值。

First Patient Dosed in a Phase 1b/2 Clinical Trial of HLX701 Combination Therapy in Advanced Colorectal Cancer

March 26, 2026, Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the first patient has been dosed in a Phase 1b/2 trial (HLX701-CRC201) evaluating its novel recombinant human SIRPα-Fc fusion protein, HLX701, in combination with cetuximab and chemotherapy in patients with advanced RAS/BRAF wild-type metastatic colorectal cancer (mCRC).

Colorectal cancer is a highly prevalent malignancy both in China and globally. In 2022, there were approximately 1.926 million new cases and 904,000 deaths worldwide, with China accounting for 517,000 new cases and 240,000 deaths, ranking second in incidence and fourth in mortality among all cancers^1-2. Standard first- and second-line treatments for advanced/metastatic colorectal cancer typically include fluoropyrimidine-based chemotherapy combined with either anti-angiogenic agents (anti-VEGF targeted therapy, e.g., bevacizumab) or anti-EGFR targeted therapy. Specifically, for patients with RAS/BRAF wild-type mCRC, cetuximab (anti-EGFR targeted agents) plus chemotherapy is one of the recommended first-line regimens. However, as the disease progresses to later lines, treatment options become more limited and increasingly depend on prior treatment response, performance status (e.g., ECOG score), and specific molecular subtypes^3-4. Later-line options^5-7 such as regorafenib, fruquintinib, and TAS-102 offer limited clinical overall benefits, underscoring a critical unmet need for more effective and combination-ready therapies. Immunotherapies targeting the CD47-SIRPα signaling pathway have entered clinical trials in colorectal cancer and other solid and hematologic malignancies. Notably, its combination regimens have shown potential synergy in specific molecular subtypes of cancer^8-9. As next-generation CD47-SIRPα-targeted therapies continue to advance, further clinical validation is warranted to establish their efficacy and optimal combination strategies.

HLX701 is a next-generation SIRPα-Fc fusion protein in-licensed from FBD Biologics Limited (“FBD”), a subsidiary of HanchorBio, and is being advanced under a collaboration agreement between the parties. This molecule is an engineered fusion protein combining a human SIRPα immunoglobulin (IgV) domain with the crystallizable fragment (Fc) region of human Immunoglobulin G4 (IgG4). It binds to CD47 on tumor cells with high affinity, effectively blocking the inhibitory CD47 "don't eat me" signaling, thereby promoting macrophage-mediated phagocytosis of tumor cells and enhancing anti-tumor activity. It further activates T cells via antigen presentation, ultimately achieving synergistic engagement of both innate and adaptive immunity.

Notably, nonclinical and early clinical data suggest that HLX701, while binding selectively and with high affinity to tumor CD47, exhibits minimal binding to CD47 on normal cells such as red blood cells (RBCs). Consequently, it neither induces RBC agglutination nor promotes macrophage-mediated RBC phagocytosis, thereby demonstrating a lower potential to cause common hematological adverse events, including anemia and thrombocytopenia, in clinical settings. In animal models, HLX701 has shown additive or synergistic antitumor activity when combined with chemotherapy, immune checkpoint inhibitors, epidermal growth factor receptor (EGFR) inhibitors, or anti-angiogenic agents across multiple tumor models, including colorectal, gastric, breast, and lung cancers. Currently, a Phase 1 dose-escalation study of HLX701 monotherapy is ongoing in both China and the U.S., and Ib/2a studies of HLX701 in combination with various agents are also underway in China.

Among them, the company's self-developed anti-PD-1 monoclonal antibody (mAb), serplulimab, is the world's first anti-PD-1 mAb approved for first-line treatment of small cell lung cancer (SCLC), and the first and only anti-PD-1 with positive results from a phase 3 registrational trial in the perioperative treatment of gastric cancer (GC). To date, it has been approved in over 40 countries and regions, including China, Germany, the UK, India, and Singapore. HLX43 is a potential best-in-class pan-tumor ADC targeting PD-L1 that integrates dual mechanisms: immune checkpoint blockade and payload-mediated cytotoxicity. It has shown broad therapeutic potential in preclinical and early clinical studies, with an encouraging safety profile and preliminary efficacy in non-small cell lung cancer (NSCLC), cervical cancer (CC), and esophageal squamous cell carcinoma (ESCC)， with ongoing validation in other solid tumors such as cervical cancer (CC) and esophageal squamous cell carcinoma (ESCC). HLX701 represents a key asset in Henlius' immuno-oncology pipeline. Its differentiated molecular design holds promise for an improved safety profile and the potential to synergize deeply with Henlius' existing pipeline assets, thereby paving the way for next-generation immuno-oncology treatment strategies.

Guided by unmet clinical needs and its antibody platform strength, Henlius will pursue novel targets with high potential, actively explore frontier technologies, and seek partnerships for premium, innovative assets to bring more quality, affordable treatment options to patients worldwide.

About HLX701-CRC201

This Phase 1b/2 clinical study compares HLX701 in combination with cetuximab and chemotherapy (FOLFOX/FOLFIRI) versus placebo in combination with cetuximab and chemotherapy (FOLFOX/FOLFIRI) in patients with recurrent, unresectable, or metastatic RAS/BRAF wild-type colorectal cancer who have previously received chemotherapy. This study consists of three stages: In Stage 1 (safety run-in), a 3+3 dose-escalation design is used, with a total of 4 dose levels ranging from 5 mg/kg to 18 mg/kg. Subjects will be treated with HLX701 in combination with cetuximab and chemotherapy at different dose levels, with intravenous administration once per week. In Stage 2, there are 3 dose groups ranging from 8 mg/kg to 18 mg/kg, administered once weekly by intravenous infusion, to evaluate the clinical efficacy and safety of HLX701 in combination with cetuximab and chemotherapy at different dose levels. Stage 3 is a randomized, double-blind, multi-center study comparing the efficacy and safety of HLX701 or placebo in combination with cetuximab and chemotherapy. The primary endpoint for Stage 1 is the proportion of dose-limiting toxicities (DLTs), while secondary endpoints include safety indicators such as adverse events, efficacy indicators such as objective response rate (ORR) and disease control rate (DCR), pharmacokinetic (PK) parameters, and immunogenicity. The primary endpoints for Stage 2 are determination of the recommended Phase 2 dose (RP2D) and the ORR and progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR). The primary endpoints for Stage 3 are the ORR and PFS as assessed by BICR. The secondary endpoints of Stage 2 and Stage 3 include safety indicators such as adverse events, efficacy endpoints (e.g., ORR and PFS assessed by investigators, overall survival [OS]), PK parameters, and immunogenicity, as well as the exploration of the association between biomarkers and efficacy.

About Henlius

Shanghai Henlius Biotech, Inc. (2696.HK) is a global, innovation-driven biopharmaceutical company committed to delivering high-quality, affordable biologic therapies to patients worldwide. The Company focuses on major disease areas including oncology, autoimmune diseases, and ophthalmic diseases. Founded in 2010, Henlius has established an integrated, end-to-end biopharmaceutical platform encompassing global R&D, clinical operations, regulatory affairs, manufacturing, and commercialisation. The Company employs nearly 4,000 people globally and operates across multiple regions, including China, the United States, and Japan. Leveraging the stable cash flow generated from its biosimilar portfolio to support innovation, Henlius is steadily advancing into its “Globalisation 2.0” phase, building a scalable and sustainable global growth model. As of early 2026, Henlius has achieved regulatory approvals for 10 products across 60 countries and regions worldwide, including seven approvals in China. The Company has also reached multiple milestones in major biopharmaceutical markets, with four products approved by the U.S. Food and Drug Administration (FDA) and four products approved by the European Commission (EC), reflecting its globally aligned R&D capabilities, quality systems, and manufacturing standards.

Driven by innovation, Henlius has built a diversified, platform-based technology ecosystem through coordinated R&D efforts across Shanghai, the United States, and other regions. Its innovation platforms span immune checkpoint inhibitors, immune cell engager technologies (including multispecific T cell engagers), antibody-drug conjugates (ADCs), and AI-enabled early discovery platforms. The Company currently has more than 50 early-stage innovative assets, approximately 70% of which are expected to be best-in-class, with over 30 clinical trials ongoing globally. Henlius’ core product, serplulimab (trade name: Hetronifly^® in Europe), is the world’s first anti–PD-1 mAb approved for first-line treatment of small cell lung cancer and has been approved in more than 40 markets worldwide with an accelerated globalisation process. In parallel, multiple high-potential innovative assets—including the PD-L1 ADC HLX43 and the novel epitope anti-HER2 mAb HLX22—are advancing through global pivotal clinical development. Supported by a biologics manufacturing network with a total capacity of 84,000L and GMP certifications from regulatory authorities in China, Europe, and the United States, Henlius has established a stable global supply system serving six continents. Guided by a patient-centred mission, Henlius remains focused on addressing unmet medical needs and translating scientific innovation into meaningful clinical value and patient access, contributing sustainably to the global biopharmaceutical ecosystem.

To learn more about Henlius, visit https://www.henlius.com/en/index.html and connect with us on LinkedIn at https://www.linkedin.com/company/henlius/.

References

1. Bray F, 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. Han B, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024 Feb 2;4(1):47-53.

3. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Colon Cancer version 5.2025

4. 2025 CSCO结直肠癌诊疗指南

5. Grothey A, et al; CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):303-12.

6. Mayer R J, et al. Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer[J]. New England Journal of Medicine, 2015, 372(20):1909-1919.

7. Li J, et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients with Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018;319(24):2486–2496.

8. Eng C, et al. A Phase 1b/2 Study of the Anti-CD47 Antibody Magrolimab with Cetuximab in Patients with Colorectal Cancer and Other Solid Tumors. Target Oncol. 2025 May;20(3):519-530.

9. Lentz RW, et al. Phase II Clinical Trial and Preclinical Evaluation of a Novel CD47 Blockade Combination in Refractory Microsatellite-Stable Metastatic Colorectal Cancer. Cancer Res Commun. 2025 Nov 1;5(11):2039-2052.

联系方式

媒体：PR@Henlius.com

投资者：IR@Henlius.com