全球研發｜漢曲優國際多中心III期臨牀研究更新結果發表於The Breast，長...

近日，由中國醫學科學院腫瘤醫院國家新藥（抗腫瘤）臨牀研究中心主任徐兵河院士牽頭開展的漢曲優（曲妥珠單抗，美國商品名：HERCESSI，歐洲商品名：Zercepac）國際多中心III期臨牀試驗HLX02-BC01（臨牀試驗號：NCT；歐洲臨牀試驗號：2016-000206-10）3年隨訪更新結果在乳腺癌領域專業期刊The Breast發表。隨訪分析結果表明，漢曲優與原研曲妥珠單抗在未經系統治療的HER2陽性轉移性乳腺癌患者中具有相似的長期療效、安全性和免疫原性，進一步驗證了其臨牀等效性。

HLX02-BC01是一項在中國、菲律賓、波蘭等89箇中心同步開展的隨機、雙盲、國際多中心的III期臨牀研究，旨在評估國產曲妥珠單抗（漢曲優）和原研曲妥珠單抗在未經系統治療的HER2陽性轉移性乳腺癌患者中的療效、安全性和免疫原性。該研究共計入組了649例受試者，受試者按照1:1的比例隨機分爲兩組，分別靜脈注射給予漢曲優聯合多西他賽或歐洲市售（EU-）曲妥珠單抗聯合多西他賽（初始劑量爲8 mg/kg，隨後每三週注射6 mg/kg，最多給藥12個月）。研究的主要終點爲24周的總緩解率（ORR24w），次要終點包括總生存期（OS）、無進展生存期（PFS）、安全性和免疫原性等。

本次發表的研究結果主要更新了PFS和OS等數據。結果顯示，在3年隨訪中，漢曲優組（n=324）中位PFS爲11.7 個月， EU-曲妥珠單抗組（n=325）中位PFS爲10.6個月，HR= 0.86 ，p = 0.158，與之前研究分析差異不大，兩組間相似。漢曲優組36個月的中位OS爲37.3個月（95% CI 36.2-不可評估），EU-曲妥珠單抗組未達到（95% CI 34.2-不可評估），HR=0.86，p = 0.229，兩組36個月的OS率分別爲57.5%和54.0%，無顯著差異。此外，漢曲優與歐洲市售曲妥珠單抗在長期安全性和免疫原性方面的結果相似。研究結果充分證明，在全球各地區招募的HER2陽性轉移性乳腺癌患者中，漢曲優與原研曲妥珠單抗在長期療效、安全性和免疫原性方面均無臨牀意義的差別。

漢曲優是中美歐三地獲批的國產單抗生物類似藥，也是獲批上市國家和地區最多的國產生物類似藥。圍繞該產品，復宏漢霖開展了一系列的頭對頭比對研究，包括質量對比研究、臨牀前研究、臨牀I期和國際多中心臨牀III期研究等，並於BioDrugs、Cancer Chemotherapy and Pharmacology、歐洲腫瘤內科學會（ESMO）、歐洲乳腺癌大會（EBCC）等國際生物醫藥領域知名期刊和學術舞臺進行發表，充分證明了漢曲優與原研曲妥珠單抗在質量、安全性和有效性方面高度相似。截至目前，漢曲優已於中國、美國、英國、加拿大、法國、德國、瑞士、澳大利亞、芬蘭、西班牙、阿根廷、沙特阿拉伯、泰國等50多個國家和地區獲批上市，覆蓋亞洲、歐洲、拉丁美洲、北美洲和大洋洲，對外授權覆蓋約100個國家和地區，並進入中國、英國、法國和德國等國家醫保目錄，惠及全球超過23萬名患者。

復宏漢霖深耕腫瘤治療領域，針對肺癌、消化道腫瘤、乳腺癌等高發瘤種的治療進行了全面佈局，豐富的管線覆蓋多款乳腺癌治療產品，其中，公司小分子抗腫瘤藥物漢奈佳（奈拉替尼）用於HER2陽性早期乳腺癌的強化輔助治療，可與漢曲優實現序貫治療，爲HER2陽性早期乳腺癌患者提供了全新的治療選擇。公司自主研發的帕妥珠單抗生物類似藥HLX11的上市註冊申請（NDA）已在中國和美國獲受理，用於治療HER2陽性乳腺癌，並將有潛力與漢曲優聯合用藥，爲患者帶來更全面、有效的治療方案。此外，公司還引進了一款處於全球III期臨牀階段的新型乳腺癌內分泌療法lasofoxifene，可用於治療ESR1突變的ER+/HER2-乳腺癌，並在2024年12月完成了中國首例患者給藥。圍繞乳腺癌，公司積極推進單藥產品和聯合療法的臨牀研究，充分發揮管線產品間的協同效應，以期覆蓋不同分型乳腺癌患者、不同疾病分期的全線治療，爲患者帶去更佳的生存獲益。

未來，復宏漢霖將持續推動漢曲優在更多國家和地區的商業化落地，進一步深化該產品在全球市場的佈局和影響力，同時加快探索創新治療方案，持續提升乳腺癌患者的生存、生活質量，爲全球患者帶去更多高質量、可負擔的治療選擇。

關於The Breast

The Breast是一本國際性的、多學科的學術期刊，專注於乳腺癌預防、診斷和治療的轉化和臨牀研究。該期刊涵蓋了乳腺癌領域的廣泛學科，包括流行病學、轉化研究、篩查、治療和護理等，爲全球研究人員和臨牀醫生提供了一個高質量的學術交流平臺。

關於復宏漢霖

復宏漢霖（2696.HK）是一家國際化的創新生物製藥公司，致力於爲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，4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製藥平臺，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範（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。

復宏漢霖前瞻性佈局了一個多元化、高質量的產品管線，涵蓋50多個分子，並全面推進基於自有抗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，歐盟商品名：Hetronifly）以及漢奈佳（奈拉替尼）。公司亦同步就16個產品在全球範圍內開展30多項臨牀試驗，對外授權全面覆蓋歐美主流生物藥市場和衆多新興市場。

Recently, the updated 3-year follow-up results of the international multicenter Phase 3 clinical trial HLX02-BC01(NCT and EudraCT: 2016-000206-10) of HANQUYOU (trastuzumab, trade name: HERCESSI in the U.S., Zercepac in Europe), led by Academician Binghe Xu, director of the National New Drug (Antitumor) Clinical Research Center of Cancer Hospital Chinese Academy of Medical Sciences, were published in the professional breast cancer journal The Breast. The follow-up analysis results demonstrated that HANQUYOU exhibited comparable long-term efficacy, safety, and immunogenicity to the reference trastuzumab in patients with previously untreated HER2-positive metastatic breast cancer, further validating their clinical equivalence.

HLX02-BC01 is a randomized, double-blind, international multicenter Phase 3 clinical study conducted across 89 centers in China, the Philippines, Poland and other countries. The study aimed to evaluate the efficacy, safety, and immunogenicity of the domestically developed trastuzumab (HANQUYOU) compared to the reference trastuzumab in previously untreated HER2-positive metastatic breast cancer patients. A total of 649 subjects were enrolled and were randomized in a 1:1 ratio to receive either HANQUYOU or the European Union (EU)-sourced trastuzumab in combination with docetaxel (initial dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks for up to 12 months). The primary endpoint was the overall response rate up to week 24 (ORR24w), with secondary endpoints including overall survival (OS), progression-free survival (PFS), safety, and immunogenicity.

The published results primarily updated PFS and OS. The findings showed that during the 36-month follow-up period, the median PFS for the HANQUYOU group (n=324) was 11.7 months, and the median PFS for the EU-trastuzumab group (n=325) was 10.6 months, HR= 0.86 ，p = 0.158, showing little difference from the previous study analysis and indicating similarity between the two groups. The median OS for the HANQUYOU group at 36 months was 37.3 months (95% CI 36.2-not evaluable), while the median OS for the EU-trastuzumab group was not reached (95% CI 34.2-not evaluable), HR=0.86，p = 0.229‍. The 36-month OS rates for the two groups were 57.5% and 54.0% respectively, with no significant difference observed. Furthermore, HANQUYOU demonstrated long-term safety and immunogenicity profiles comparable to those of the EU-sourced trastuzumab. These results conclusively demonstrate that, among HER2-positive metastatic breast cancer patients recruited globally, HANQUYOU and the reference trastuzumab exhibit no clinically meaningful differences in long-term efficacy, safety, and immunogenicity.

HANQUYOU is the first China-developed monoclonal antibody biosimilar to receive approval in China, the U.S., and Europe, making it the most widely approved Chinese biosimilar across multiple countries and regions. Henlius has conducted a series of head-to-head comparative studies for this product, including quality comparison studies, preclinical studies, Phase 1 clinical trials, and international multicenter Phase 3 clinical trials. The results have been published in renowned international biomedical journals and conferences such as BioDrugs, Cancer Chemotherapy and Pharmacology, the European Society for Medical Oncology (ESMO), and the European Breast Cancer Conference (EBCC). These data robustly demonstrate that HANQUYOU is highly comparable to the reference trastuzumab in terms of quality, safety, and efficacy. To date, HANQUYOU has gained marketing approval in over 50 countries and regions, including China, the U.S., the U.K., Canada, France, Germany, Switzerland, Australia, Finland, Spain, Argentina, Saudi Arabia, and Thailand, spanning Asia, Europe, Latin America, North America, and Oceania. The product has also been licensed in approximately 100 countries and regions and has been included in the national medical insurance catalogs of countries such as China, the UK, France, and Germany, benefiting over 230,000 patients globally.

Henlius has been deeply committed to the field of oncology, with a comprehensive portfolio targeting high-incidence cancers such as lung cancer, gastrointestinal tumors, and breast cancer. Its robust pipeline includes multiple breast cancer treatments, among which HANNAIJIA (neratinib), approved for the extended adjuvant treatment of HER2-positive early breast cancer, can be used in sequential therapy with HANQUYOU, offering a new treatment option for HER2-positive early breast cancer patients. The company’s self-developed pertuzumab biosimilar, HLX11, has had its New Drug Application (NDA) accepted in China and the U.S. for the treatment of HER2-positive breast cancer. It has the potential to be used in combination with HANQUYOU, providing patients with a more comprehensive and effective treatment regimen. Additionally, the company has acquired a novel endocrine therapy for breast cancer, lasofoxifene, which is currently in global Phase 3 clinical trials, targeting ESR1-mutated ER+/HER2- breast cancer. The first patient in China was dosed in December 2024. Henlius is actively advancing clinical studies on both monotherapies and combination therapies, leveraging the synergistic effects among its pipeline products. This strategy aims to address the full spectrum of breast cancer patients across different stages and subtypes, providing comprehensive treatment options and thereby maximizing clinical benefits to patients.

Moving forward, Henlius will accelerate the commercialization of HANQUYOU in more countries and regions, further expanding its global market presence and influence. The company will also continue to advance its commercialization efforts while actively exploring innovative treatment options. These initiatives aim to improve survival rates and quality of life for breast cancer patients, as well as provide global patients with more high-quality and affordable treatment options.

About The Breast

The Breast is an international, multidisciplinary academic journal focusing on translational and clinical research in breast cancer prevention, diagnosis, and treatment. The journal covers a wide range of disciplines in the field of breast cancer, including epidemiology, translational research, screening, treatment, and care, providing a high-quality academic exchange platform for researchers and clinicians 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 4 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 over 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 the EU), 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 16 products, expanding its presence in major markets as well as emerging markets.

(復星醫藥)