（來源：復星醫藥）

轉自：復星醫藥

2025年7月14日，復星醫藥子公司復宏漢霖（2696.HK）宣布，公司創新型抗HER2單抗HLX22頭對頭對比一線標準療法（曲妥珠單抗+化療±帕博利珠單抗）的國際多中心III期研究（HLX22-GC-301）完成美國首例患者給藥，擬用于聯合曲妥珠單抗及化療一線治療HER2陽性晚期胃癌。目前，全球尚無同類用于治療HER2陽性胃癌的HER2雙靶向療法獲批準上市。

HLX22-GC-301由北京大學腫瘤醫院沈琳教授與NCCN胃癌與食管癌專委會主席，MD安德森癌癥中心的Jaffer A. Ajan教授牽頭開展，此前已于中國、日本、澳大利亞、韓國完成首例受試者給藥，并已在智利、巴西、阿根廷等國家和地區獲得臨床試驗開展許可。此外，HLX22已于2025年獲得美國食品藥品監督管理局（FDA）和歐盟委員會（EC）授予的孤兒藥資格認定（Orphan Drug Designation, ODD），用于胃癌的治療。

據GLOBOCAN數據顯示，2022年全球約有100萬胃癌新發病例，逾66萬死亡病例，疾病負擔呈現顯著地域不平衡[1]，構成了一大健康問題。多數胃癌患者早期癥狀隱匿，確診時已處于疾病晚期，總體預后不良，5年生存率僅為6%[2,3]。盡管近年來靶向治療（如抗HER2藥物）和免疫檢查點抑制劑（如抗PD-1/PD-L1單抗）在胃癌的治療中取得了一定進展[4]，但鑒于該疾病具有高度分子異質性，不同亞型患者對化療、靶向治療和免疫治療的反應差異顯著[5]。免疫治療局限于PD-L1陽性人群，且療效改善有限。胃癌尤其是HER2陽性胃癌的整體治療仍存在巨大的未滿足的臨床需求。

HLX22為靶向HER2的創新型單克隆抗體，可結合在HER2的胞外亞結構域IV，但結合表位與曲妥珠單抗有所不同，使得該產品能夠與曲妥珠單抗同時結合至HER2，有效促進HER2二聚體（HER2同源二聚體及HER2/EGFR異源二聚體）的內吞和降解，將HER2的內吞效率提高了40%-80%，進而產生更強的HER2受體阻斷效果。HLX22聯合漢曲優?（曲妥珠單抗，美國商品名：HERCESSI??，歐洲商品名：Zercepac?）治療HER2陽性胃癌II期臨床研究（HLX22-GC-201）更新結果于2025年美國臨床腫瘤學會（ASCO）發布[6]，數據顯示經過長期隨訪（中位隨訪周期超2年），HLX22在HER2陽性胃癌治療中依然展現出穩定的療效獲益，遠超歷史數據。

HLX22-GC-301臨床研究是一項雙盲、國際多中心隨機對照III期研究，旨在比較HLX22聯合曲妥珠單抗和化療對比曲妥珠單抗和化療聯合或不聯合帕博利珠單抗，一線治療HER2陽性局部晚期或轉移性胃癌/胃食管結合部癌患者的療效和安全性。符合條件的受試者將以1:1的比例隨機分配至試驗組（接受HLX22（15 mg/kg）聯合曲妥珠單抗和化療）或對照組（接受安慰劑聯合曲妥珠單抗和化療，聯合或不聯合帕博利珠單抗）。該研究的主要終點為獨立影像評估委員會（IRRC）基于RECIST v1.1評估的無進展生存期（PFS）和總生存期（OS）。次要終點包括研究者評估的PFS、IRRC或研究者評估的客觀緩解率（ORR）、下一線治療的PFS2、緩解持續時間（DOR）、生活質量、安全性、免疫原性和藥代動力學特征。

除胃癌外，復宏漢霖近期亦啟動一項HLX22聯合德曲妥珠單抗治療HER2低表達HR陽性乳腺癌的II期臨床研究（HLX22-BC201）并于中國境內完成首例患者給藥。未來，復宏漢霖也將持續探索新型抗HER2靶向療法在腫瘤中的治療潛力，高效推進HLX22的全球臨床開發進展，為全球患者提供更多可負擔、療效更好的治療方案。

參考文獻

[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 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

關于復宏漢霖

復宏漢霖（2696.HK）是一家國際化的創新生物制藥公司，致力于為全球患者提供可負擔的高品質生物藥，產品覆蓋腫瘤、自身免疫疾病、眼科疾病等領域，已有6款產品在中國獲批上市，4款產品在國際獲批上市，5個上市申請分別獲中國藥監局、美國FDA和歐盟EMA受理。自2010年成立以來，復宏漢霖已建成一體化生物制藥平臺，高效及創新的自主核心能力貫穿研發、生產及商業運營全產業鏈。公司已建立完善高效的全球創新中心，按照國際藥品生產質量管理規范（GMP）標準進行生產和質量管控，不斷夯實一體化綜合生產平臺，其中，公司商業化生產基地已相繼獲得中國、歐盟和美國GMP認證。

復宏漢霖前瞻性布局了一個多元化、高質量的產品管線，涵蓋約50個分子，并全面推進基于自有抗PD-1單抗H藥漢斯狀?的腫瘤免疫聯合療法。截至目前，公司已獲批上市產品包括國內首個生物類似藥漢利康?（利妥昔單抗）、自主研發的中美歐三地獲批單抗生物類似藥漢曲優?（曲妥珠單抗，美國商品名：HERCESSI?，歐洲商品名：Zercepac?）、漢達遠?（阿達木單抗）、漢貝泰?（貝伐珠單抗）、全球首個獲批一線治療小細胞肺癌的抗PD-1單抗漢斯狀?（斯魯利單抗，歐洲商品名：Hetronifly?）以及漢奈佳?（奈拉替尼）。公司亦同步就19個產品在全球范圍內開展30多項臨床試驗，對外授權全面覆蓋歐美主流生物藥市場和眾多新興市場。

Shanghai, China, July 14, 2025 — Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the first patient in the United States has been dosed in the company’s international multicentre phase 3 head-to-head clinical trial (HLX22-GC-301) comparing its novel anti-HER2 monoclonal antibody (mAb) HLX22 in combination with trastuzumab and chemotherapy with the current first-line standard of care therapy (trastuzumab + chemotherapy ± pembrolizumab) as the first-line treatment for HER2-positive advanced gastric cancer. As of now, no similar dual HER2 blockade therapy for the treatment of HER2-positive gastric cancer has received approval for commercialization globally.

The study is co-led by Prof. Lin Shen from Peking University Cancer Hospital and Professor Jaffer A. Ajani (MD Anderson Cancer Center; Chair of the NCCN Guidelines Panel for Gastric and Esophageal Cancers), and has previously dosed first patients in China, Japan, Australia, and South Korea, with investigational new drug (IND) approvals obtained in Chile, Brazil, Argentina and other countries and regions. HLX22 has been granted Orphan Drug Designation (ODD) by both the US Food and Drug Administration (FDA) and the European Commission (EC) for the treatment of gastric cancer.

Until 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, 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. Updated results from a phase 2 study (HLX22-GC-201) of HLX22 in combination with HANQUYOU (trastuzumab, trade name: HERCESSI? in the U.S., Zercepac? in Europe) and chemotherapy as a first-line treatment for HER2-positive advanced gastric cancer were presented at ASCO 2025 [6]. The data demonstrated that the efficacy benefit of HLX22 in HER2-positive gastric cancer remained stable with extended follow-up (median follow-up exceeding two years), outperforming previous data.

This double-blind, randomized, controlled multicenter phase 3 study aims to compare the efficacy and safety of HLX22 in combination with Trastuzumab and chemotherapy versus trastuzumab and chemotherapy with or without pembrolizumab as first-line treatment in patients with HER2-positive, locally advanced or metastatic gastroesophageal junction cancer and gastric cancer. Eligible participants will be randomized at 1:1 to the experimental arm (treated with HLX22 (15 mg/kg) in combination with Trastuzumab and chemotherapy) or the control group (placebo plus Trastuzumab and chemotherapy with or without pembrolizumab). The primary endpoints of this study are progression-free survival (PFS) assessed by independent radiology review committee (IRRC) per RECIST v1.1 and overall survival (OS), the secondary endpoints include investigator-assessed PFS, IRRC or investigator-assessed objective response rate (ORR), PFS2, duration of response (DOR), quality of life, safety, immunogenicity and pharmacokinetic characteristics.

Beyond gastric cancer, Henlius has also recently initiated a phase 2 clinical trial (HLX22-BC201) of HLX22 in combination with trastuzumab deruxtecan (T-DXd) as second-line therapy for HER2-low, hormone receptor (HR)-positive locally advanced or metastatic breast cancer and has dosed the first patient in China. 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 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.