2025年6月2日，复宏汉霖（2696.HK）宣布，公司创新型抗HER2单抗HLX22的最新研究结果在2025年美国临床肿瘤学会（ASCO）年会上公布，包括HLX22联合曲妥珠单抗及化疗一线治疗HER2阳性晚期胃癌的II期临床研究（HLX22-GC-201）的疗效与安全性超两年随访更新数据，以及头对头对比一线标准疗法（曲妥珠单抗+化疗±帕博利珠单抗）的国际多中心III期临床研究（HLX22-GC-301）的研究设计首次发布。HLX22-GC-201研究更新数据显示，经过长期随访，HLX22在HER2阳性胃癌治疗中依然展现出稳定的疗效获益，远超历史数据。HLX22-GC-301研究正在全球范围内高效推进并已在多地完成首例患者给药。目前，全球尚无同类用于治疗HER2阳性胃癌的HER2双靶向疗法获批准上市。双靶向双表位结合HER2突破胃癌一线治疗桎梏据GLOBOCAN数据显示，2022年全球约有100万胃癌新发病例，逾66万死亡病例，疾病负担呈现显著地域不平衡[1]，构成了一大健康问题。多数胃癌患者早期症状隐匿，确诊时已处于疾病晚期，总体预后不良，5年生存率仅为6%[2,3]。尽管近年来靶向治疗（如抗HER2药物）和免疫检查点抑制剂（如抗PD-1/PD-L1单抗）在胃癌的治疗中取得了一定进展[4]，但鉴于该疾病具有高度分子异质性，不同亚型患者对化疗、靶向治疗和免疫治疗的反应差异显著[5]。免疫治疗局限于PD-L1阳性人群，且疗效改善有限。胃癌尤其是HER2阳性胃癌的整体治疗仍存在巨大的未满足的临床需求。HLX22是一款靶向HER2的创新型单克隆抗体，已于2025年获得美国食品药品监督管理局（FDA）和欧盟委员会（EC）授予的孤儿药资格认定（Orphan Drug Designation, ODD），用于胃癌的治疗。HLX22可结合在HER2的胞外亚结构域IV，但结合表位与曲妥珠单抗有所不同，使得该产品能够与曲妥珠单抗同时结合至HER2，有效促进HER2二聚体（HER2同源二聚体及HER2/EGFR异源二聚体）的内吞和降解，将HER2的内吞效率提高了40%-80%，进而产生更强的HER2受体阻断效果。临床前研究表明，HLX22与曲妥珠单抗联合治疗能够协同抑制肿瘤细胞增殖和诱导细胞凋亡，在体内和体外均表现出增强的抗肿瘤活性。II期研究数据亮点：超2年随访，明显延长PFS和OSHLX22联合汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™️，欧洲商品名：Zercepac®）治疗HER2阳性胃癌的II期临床研究（HLX22-GC-201）结果显示，在汉曲优®联用化疗的基础上加入HLX22可提高HER2阳性G/GEJ癌患者一线治疗的生存期和抗肿瘤反应，且安全性可控，有望重塑晚期胃癌的一线标准治疗。该研究结果数据首次发布于2024年美国临床肿瘤学会胃肠道肿瘤研讨会（ASCO GI），其后该研究数据及数据更新亦分别获选发布于Med和2024年欧洲肿瘤学会胃肠道肿瘤研讨会（ESMO GI）、2025年美国临床肿瘤学会胃肠道肿瘤研讨会（ASCO GI）[6-9]，多次验证了研究结果可靠性的同时，更进一步提升了该研究在学术界的影响力。HLX22-GC-201研究纳入未经系统治疗的局部晚期或转移性HER2阳性胃/胃食管结合部癌（G/GEJC）患者，按1:1随机分配至HLX22+曲妥珠单抗+XELOX组或安慰剂+曲妥珠单抗+XELOX组，每3周为一个治疗周期。主要终点为独立影像评估委员会（IRRC）根据实体瘤评价标准（RECIST v1.1）评估的无进展生存期（PFS）和客观缓解率（ORR）；次要终点包括其他疗效及安全性指标。截至2024年12月6日，共有62名患者被随机分组（31 vs 31），其中51名（82.3%）为男性。两组中位随访周期分别为28.5个月和28.7个月。主要有效性结果参见表1。两组分别有30例（96.8%）和31例（100%）患者报告了治疗期间不良事件（TEAEs）。17例（54.8%）和15例（48.4%）患者中发生了3级或以上的TEAEs。安慰剂+曲妥珠单抗+XELOX组中，1例（3.2%）患者发生了HLX22或安慰剂相关的导致死亡的治疗期不良事件（TEAE）。两组各有1例患者（3.2%）报告与HLX22/安慰剂相关的导致治疗终止的TEAE。HLX22-GC-201研究更新结果再次应证了HLX22联合曲妥珠单抗及化疗为HER2阳性G/GEJC患者带来明显的临床获益，且安全性可控。III期头对头研究设计：国际多中心试验全球加速推进基于前瞻性HLX22-GC-201研究，公司进一步在更多人群中评价HLX22联合曲妥珠单抗及化疗一线治疗HER2阳性晚期胃癌的疗效与安全性，并开展一项头对头国际多中心III期临床研究（HLX22-GC-301）。HLX22-GC-301由北京大学肿瘤医院沈琳和MD安德森癌症中心教授、NCCN胃癌与食管癌专委会主席Jaffer A. Ajani教授共同担任牵头主要研究者。此次ASCO大会首次公布HLX22-GC-301的试验设计，该研究是一项随机、双盲、双臂、国际多中心III期临床试验，旨在比较HLX22联合曲妥珠单抗及XELOX方案与曲妥珠单抗及XELOX联合或不联合帕博利珠单抗一线治疗HER2阳性晚期胃/胃食管结合部（G/GEJ）癌的疗效与安全性。HLX22-GC-301关键入选标准包括经组织学或细胞学确诊、既往未接受治疗的局部晚期不可切除或转移性、HER2阳性G/GEJ腺癌；关键排除标准包括既往接受过任何HER2靶向治疗。研究计划从全球多个地区入组约550例患者，按1:1随机分配接受以下治疗：HLX22（15 mg/kg）联合曲妥珠单抗及XELOX±帕博利珠单抗安慰剂，或HLX22安慰剂联合曲妥珠单抗及XELOX±帕博利珠单抗。HLX22的给药在每个21天的治疗周期的第1天通过静脉输注进行，持续给药至丧失临床获益、死亡、出现不可耐受毒性、撤回知情同意或其他原因终止。分层因素包括HER2免疫组化评分（3+相比2+）、地理区域（亚洲相比欧洲/北美相比其他地区）、肿瘤原发部位（胃相比胃食管结合部）及肿瘤PD-L1表达（CPS <1或不可评估相比1≤CPS<10相比CPS≥10）。共同主要终点为独立影像评估委员会基于实体瘤疗效评价标准（RECIST v1.1）评估的无进展生存期（PFS），以及总生存期（OS）；次要终点包括研究者评估的PFS、客观缓解率、后续治疗线的PFS、缓解持续时间、安全性、药代动力学、免疫原性及生活质量。值得一提的是，HLX22-GC-301同步于中国、澳大利亚、欧盟、日本、美国、南美洲等国家和地区开设试验中心。截至目前，该研究已于中国、日本、澳大利亚完成首例受试者给药，并已在美国、智利、韩国等国家和地区获得临床试验开展许可。继HER2阳性胃癌之后，HLX22的治疗领域已逐步拓宽至乳腺癌疾病领域。2025年4月，HLX22单抗联合德曲妥珠单抗治疗HER2低表达HR阳性的局部晚期或转移性乳腺癌的II期临床研究（HLX22-BC201）于中国境内完成首例患者给药。HLX22联合德曲妥珠单抗的临床前动物试验显示，该抗HER2联合疗法展现出协同抗肿瘤作用和良好的安全性，有望为HER2表达肿瘤患者带来更多获益。未来，复宏汉霖也将持续探索新型抗HER2靶向疗法在肿瘤中的治疗潜力，高效推进HLX22的全球临床开发进展，为全球患者提供更多可负担、疗效更好的治疗方案。参考文献[1] Bray F, Laversanne M, Sung H, et al. CA Cancer J Clin. 2024: 1-35.[2] Ajani JA. et al. J Natl Compr Canc Netw 2022;20(2):167-92.[3] Alsina M. et al. Nat Rev Gastroenterol Hepatol 2023;20(3):155-70.[4] Miao, ZF.,et al. Progress and remaining challenges in comprehensive gastric cancer treatment. Holist Integ Oncol 1, 4 (2022).[5] Guan, WL.,et al. Gastric cancer treatment: recent progress and future perspectives. J Hematol Oncol 16, 57 (2023). [6] Jin Li et al., HLX22 plus HLX02 and XELOX for first-line treatment of HER2-positive locally advanced or metastatic gastric/gastroesophageal junction cancer: A randomized, double-blind, multicenter phase 2 study.. JCO 42, 354-354(2024).DOI:10.1200/JCO.2024.42.3_suppl.354[7] J. Li et al., 422P HLX22 plus HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric/gastroesophageal junction cancer: Updated results from a randomized, double-blind phase II study, Annals of Oncology,Annals of Oncology (2024) 35 (suppl_1): S162-S204. 10.1016/annonc/annonc1482[8] Li N, et al. A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer. Med. 2024;5(10):1255-1265.e2. [9] Jin Li et al. HLX22 plus trastuzumab and XELOX for first-line treatment of HER2-positive locally advanced or metastatic gastric/gastroesophageal junction cancer (G/GEJC): Updated results with additional patients.. JCO 43, 440-440(2025). DOI:10.1200/JCO.2025.43.4_suppl.440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。Henlius Unveils Updated Phase 2 Results and Phase 3 Trial Design for Anti-HER2 mAb HLX22 in First-Line HER2+ Gastric CancerOn June 2, 2025, Henlius (2696.HK) announced that the latest research results of novel anti-HER2 monoclonal antibody (mAb) HLX22 were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. These included updated efficacy and safety data with over two years of follow-up from the phase 2 clinical study (HLX22-GC-201) evaluating HLX22 in combination with trastuzumab and chemotherapy as a first-line treatment for HER2-positive advanced gastric cancer, as well as the debut of the study design for the international multicentre phase 3 clinical trial (HLX22-GC-301), which features a head-to-head comparison with the first-line standard of care therapy (trastuzumab + chemotherapy ± pembrolizumab).Updated data from the HLX22-GC-201 study demonstrated that the efficacy benefit of HLX22 in HER2-positive gastric cancer remained stable with extended follow-up, outperforming previous data. Meanwhile, the HLX22-GC-301 study is progressing efficiently worldwide and has already completed its first patient dosing in multiple countries and regions. As of now, no similar dual HER2 blockade therapy for the treatment of HER2-positive gastric cancer has received approval for commercialization globally.Dual-Blockade, Dual-Epitope HER2 Therapy Breaks Through First-Line Treatment Barriers in Gastric CancerUntil now, gastric cancer still constitutes a major global health problem. According to GLOBOCAN 2022, there were around 1 million new cases and over 660 thousand new deaths of gastric cancer in 2022 globally [1]. Gastric cancer is often diagnosed at an advanced stage, with a poor prognosis and a 5-year relative survival rate of only 6%[2,3]. Despite the advancements in targeted therapies, such as anti-HER2 agents, and immune checkpoint inhibitors (anti-PD-1/PD-L1 mAbs) for gastric cancer treatment in recent years[4], the disease's high molecular heterogeneity leads to markedly varied responses to chemotherapy, targeted therapy, and immunotherapy across different subtypes[5]. Immunotherapy remains limited to PD-L1 positive populations with only modest efficacy improvements. This underscores the urgent unmet clinical needs in the overall management of HER2 positive gastric cancer.HLX22, an innovative anti-HER2 mAb, was granted Orphan Drug Designation (ODD) from both the FDA and the EC for the treatment of gastric cancer. HLX22 can bind to HER2 extracellular subdomain IV at a binding site different from that of trastuzumab via differentiated molecular design and mechanism of action, which allows simultaneous binding of HLX22 and trastuzumab to HER2 dimers (HER2 homodimer and HER2/EGFR heterodimer) on tumour cell surface, resulting in a 40%–80% increase in HER2 internalisation. thereby strengthening the blockade of HER2-mediated signalling pathways. Pre-clinical studies showed that the co-treatment with HLX22 and trastuzumab synergistically inhibited tumour cell proliferation and apoptosis, which led to enhanced anti-tumour activity in vitro and in vivo. Phase 2 Data Highlights: Significantly Prolonged PFS & OS with Over Two Years of Follow-UpThe phase 2 clinical data on the combination of HLX22 and HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe) demonstrate that the addition of HLX22 to trastuzumab plus chemotherapy significantly improves survival and anti-tumour efficacy in first-line treatment of HER2-positive gastric/gastroesophageal junction cancer (GC/GEJC) patients, with manageable safety profiles. This combination holds potential to redefine the first-line standard of care for advanced gastric cancer.The study data were first presented at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI). Subsequent updates were also showcased at prominent journal and conferences, including Med, the 2024 ESMO Gastrointestinal Cancers Congress (ESMO GI), and the 2025 ASCO GI [6-9]. These repeated recognitions not only further solidified the reliability of the findings but also significantly enhanced the study’s influence within the research community.Patients with locally advanced or metastatic HER2+ G/GEJC and no prior systemic antitumor therapy were enrolled in HLX22-GC-201 and randomized in a 1: 1 ratio to receive either HLX22 + trastuzumab + XELOX or placebo + trastuzumab + XELOX in 3-week cycles. Primary endpoints were independent radiology review committee (IRRC)-assessed progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included other efficacy and safety endpoints.As of December 6, 2024, 62 patients were randomized to the respective groups (31 vs 31), of whom 51 (82.3%) were male. Median follow-up duration was 28.5 and 28.7 months for the respective groups. Major efficacy findings are shown in Table 1. Treatment-emergent adverse events (TEAEs) were reported in 30 (96.8%) and 31 (100%) patients, respectively. TEAEs of grade 3 or higher were observed in 17 (54.8%) and 15 (48.4%) patients. HLX22- or placebo-related TEAE leading to death occurred in 1 (3.2%) patient in the placebo + trastuzumab + XELOX group. One patient (3.2%) in each group reported HLX22/placebo-related TEAEs leading to treatment discontinuation. The updated results of HLX22-GC-201 again demonstrated that combination of chemotherapy and dual HER2 blockade with HLX22 and trastuzumab conferred survival benefit to HER2-positive G/GEJC patients along with a manageable safety profile.Phase 3 Head-to-Head Trial Design: Global Acceleration of MRCTBased on the prospective HLX22-GC-201 study, the company further evaluated the efficacy and safety of HLX22 in combination with trastuzumab and chemotherapy as a first-line treatment for HER2-positive advanced gastric cancer across broader populations. A head-to-head international multicentre phase 3 clinical trial (HLX22-GC-301) was subsequently initiated.Co-led by Prof. Lin Shen from Peking University Cancer Hospital and Prof. Jaffer A. Ajani (MD Anderson Cancer Center; Chair of the NCCN Guidelines Panel for Gastric and Esophageal Cancers) as global principal investigators, the trial design of HLX22-GC-301 was unveiled for the first time at the 2025 ASCO. This randomized, double-blinded, two-arm international phase 3 clinical study aims to compare the efficacy and safety of HLX22 in combination with trastuzumab and XELOX versus trastuzumab and XELOX with or without (±) pembrolizumab in patients with HER2-positive, advanced G/GEJ cancer and no prior antitumor therapy in the advanced setting.The study’s key inclusion criteria include histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2-positive G/GEJ adenocarcinoma. Key exclusion criteria include prior use of any HER2-target therapy. Approximately 550 eligible patients will be enrolled from multiple regions across the globe and randomly assigned in a 1:1 ratio to receive HLX22 (15 mg/kg) + trastuzumab + XELOX ± placebo (for pembrolizumab) or placebo (for HLX22) + trastuzumab + XELOX ± pembrolizumab. HLX22 will be administered intravenously on Day 1 of each 21-day treatment cycle until loss of clinical benefit, death, intolerable toxicity, withdrawal of informed consent, or other reasons. The stratification factors include HER2 immunohistochemistry (3+ vs 2+), geographic region (Asia vs Europe/North America vs rest of the world), primary tumour site (gastric vs gastroesophageal junction), and tumour PD-L1 expression (CPS < 1 or not evaluable vs 1 ≤ CPS < 10 vs CPS ≥ 10). The dual primary endpoints are PFS assessed by independent radiology review committee per RECIST v1.1 and overall survival. Secondary endpoints include investigator-assessed PFS, objective response rate, PFS on the subsequent line of therapy, duration of response, safety, pharmacokinetics, immunogenicity, and quality of life.Notably, HLX22-GC-301 has set up trial sites across China, Australia, the European Union, Japan, the United States, South America, and other countries and regions. As of now, the first patient was dosed in China, Japan, and Australia, and the study has obtained investigational new drug (IND) approvals in countries and regions including the United States (U.S.), Chile and Korea. Following its focus on HER2-positive gastric cancer, HLX22’s therapeutic scope has expanded into breast cancer. In April 2025, a phase 2 clinical trial (HLX22-BC201) of HLX22 in combination with trastuzumab deruxtecan (T-DXd) has completed the first patient dosing for the treatment of HER2-low, hormone receptor (HR)-positive locally advanced or metastatic breast cancer in China. Preclinical animal studies of HLX22 combined with T-DXd showed synergistic anti-tumour effect and good safety profiles, which may offer more benefits to patients with HER2-expressing tumours. Moving forward, Henlius will continue to explore the therapeutic potential of novel HER2-targeted therapies in tumours, accelerating HLX22’s global development to deliver more affordable and effective treatment options for patients worldwide.About HenliusHenlius (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.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
