重磅!全球首個登上國際頂級期刊JAMA的小細胞肺癌免疫治療臨床研究:H藥漢斯狀

金融界 發佈 2022-09-28T07:03:48.064787+00:00

HANSIZHUANG is the first innovative monoclonal antibody developed by Henlius. Up to date, 1 indication is approved for marketing in China, 3 NDAs have been accepted by the NMPA, and 11 clinical trials are ongoing across the world.

2022年9月27日,由程穎教授牽頭的國際多中心研究——ASTRUM-005研究在全球四大頂級醫學期刊之一的《美國醫學會雜誌》(JAMA,影響因子:157.3)在線發表,成為全球首個登上JAMA主刊的小細胞肺癌免疫治療臨床研究。ASTRUM-005研究是復宏漢霖自主研發的抗PD-1單抗H藥 漢斯狀®(斯魯利單抗)聯合化療一線治療廣泛期小細胞肺癌(ES-SCLC)的Ⅲ期臨床研究,2022年ASCO年會程穎教授首次報告結果後,引起了全球同行的廣泛關注,而今再度登上國際頂級學術舞台,體現了國際學術界的高度認可,彰顯出中國研究者的智慧化和生物醫藥領域國際一流的自主創新實力和臨床運營能力。

程穎教授

通訊作者與第一作者、ASTRUM-005研究主要研究者、吉林省腫瘤醫院程穎教授表示:

ASTRUM-005研究中斯魯利單抗聯合化療獲得了目前廣泛期小細胞肺癌免疫一線治療中最長的OS結果,與化療相比可以延長4.5個月的生存,迄今為止最低的HR:0.63,而且近期療效和遠期療效的結果一致,同時具有良好的安全性。這項研究首次證實了PD-1抑制劑聯合化療同樣能夠改善廣泛期小細胞肺癌的生存,這也是由我們中國研究者牽頭的首個針對ES-SCLC適應症免疫治療的國際多中心臨床Ⅲ期研究,充分彰顯了中國研究者的實力。感謝所有在該研究中做出貢獻的患者及家屬的配合,也感謝其他研究者的付出,這項研究為廣泛期小細胞肺癌一線免疫治療展開了新的一頁,為廣大患者帶去福音。

OS達15.4個月,刷新一線小細胞肺癌總生存期紀錄

小細胞肺癌(SCLC)約占肺癌總數的15%,是肺癌中侵襲性最強的亞型,分為局限期小細胞肺癌(LS-SCLC)和ES-SCLC。二者共同點是惡性程度高、轉移早、疾病進展迅速,總體預後不良。近些年,免疫檢查點抑制劑的出現為ES-SCLC領域的治療帶來新希望,抗PD-L1單抗聯合化療已被國內外權威指南推薦為ES-SCLC一線治療方案,相較化療一定程度上改善了患者總生存期,然而改善程度相對有限,仍需要更有效治療方案。

ASTRUM-005是一項在既往未接受過治療的ES-SCLC患者中比較H藥聯合化療及安慰劑聯合化療的臨床有效性和安全性的隨機、雙盲、國際多中心、Ⅲ期臨床研究,在中國、土耳其、歐盟波蘭、喬治亞等多個國家共開設128個試驗中心,其中114個試驗中心有受試者參與了篩選,共入組585例受試者,約31.5%為白人。截至2021年10月22日,本研究共入組的斯魯利單抗組(n=389)和安慰劑組(n=196)中位隨訪時間為12.3個月。斯魯利單抗組和安慰劑組的中位OS分別為15.4個月(95% CI 13.3–NE)和10.9個月(95% CI 10.0–14.3),風險比(HR)為0.63(95% CI 0.49–0.82;p<;;0.001)。兩組的24個月總生存率分別為43.1%和7.9%。斯魯利單抗組及安慰劑組經獨立影像評估委員會(IRRC)依據RECIST v1.1評估的中位PFS分別為5.7和4.3個月(HR 0.48,95% CI 0.38–0.59)。安全性方面,斯魯利單抗組的免疫相關不良事件(irAEs)發生率與已獲批的PD-1/PD-L1單抗相似。

有望惠及全球患者,填補未來五年臨床空白

ASTRUM-005研究的成功是PD-1抑制劑治療ES-SCLC的重大突破,基於該項研究,國家藥品監督管理局(NMPA)已受理H藥一線治療ES-SCLC適應症的上市申請;《CSCO小細胞肺癌診療指南(2022版)》也新增斯魯利單抗聯合化療EC方案作為ES-SCLC一線治療推薦,為中國ES-SCLC一線治療提供了更多的選擇。不僅如此,H藥用於治療SCLC於2022年4月獲美國食品藥品監督管理局(FDA)孤兒藥資格認定。同時,基於FDA針對H藥治療ES-SCLC遞交上市申請的正向反饋及FDA C類諮詢會議的討論結果,公司將在美國啟動一項橋接臨床試驗,並擬於2024年Q1前在美國遞交相應的上市申請。目前全球尚無一線治療SCLC的抗PD-1單抗獲批,H藥有望成為全球首個一線治療SCLC的抗PD-1單抗,填補未來五年PD-1抑制劑一線治療小細胞肺癌的臨床空白。

未來,復宏漢霖將持續加碼創新,以臨床需求為先導,繼續高效地為全球患者提供更多可負擔、療效更好的治療方案。

關於JAMA

JAMA是同行評審的國際綜合性醫學期刊,以促進醫學的科學與藝術以及改善公共衛生為主要目標。自1883年連續出版以來,JAMA已成為醫學和科學領域最具影響力的期刊之一,目前影響因子為157.3。JAMA也是世界上發行最廣泛的綜合性醫學類期刊,印刷版訂閱數超過29萬,網絡訂閱數超過160萬,期刊網站的年訪問量超過3800萬,具有強大的社交媒體影響力和國際新聞媒體的曝光率。

關於H藥 漢斯狀®

H藥 漢斯狀®為重組人源化抗PD-1單抗注射液(通用名:斯魯利單抗注射液),是復宏漢霖首個自主研發的創新型單抗,目前1項適應症獲批上市,3項適應症上市申請獲受理,11項臨床試驗同步在全球開展。

2022年3月,H藥正式獲批用於治療微衛星高度不穩定(MSI-H)實體瘤。圍繞H藥,復宏漢霖積極推進其與公司其他產品的協同以及與創新療法的聯合,相繼獲得中國、美國、歐盟等國家及地區的臨床試驗許可,在全球同步開展11項腫瘤免疫聯合療法臨床試驗,廣泛覆蓋肺癌、食管癌、頭頸鱗癌和胃癌等適應症,全面覆蓋肺癌一線治療。截至目前,H藥已於中國、土耳其、波蘭、喬治亞等國家和地區累計入組超3100人,其中2項國際多中心臨床試驗入組白人的比例超過30%,是擁有國際臨床數據較多的抗PD-1單抗之一。H藥聯合化療一線治療鱗狀非小細胞肺癌(sqNSCLC)、廣泛期小細胞肺癌(ES-SCLC)和食管鱗狀細胞癌(ESCC)的NDA已獲得NMPA受理,H藥有望成為全球首個一線治療SCLC的抗PD-1單抗。此外,該藥入選《2022 CSCO小細胞肺癌診療指南》作為ES-SCLC治療推薦,針對ES-SCLC的國際多中心臨床研究ASTRUM-005成為全球首個登上JAMA的小細胞肺癌免疫治療臨床研究,其治療小細胞肺癌(SCLC)也已獲得美國FDA孤兒藥資格認定。

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,已在中國上市5款產品,在國際上市1款產品,13項適應症獲批,5個上市註冊申請獲得中國藥監局受理。自2010年成立以來,復宏漢霖已建成一體化生物製藥平台,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台,其中,上海徐匯基地已獲得中國和歐盟GMP認證,松江基地(一)也已獲得中國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20多種創新單克隆抗體,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。繼國內首個生物類似藥漢利康®(利妥昔單抗)、中國首個自主研發的中歐雙批單抗藥物漢曲優®(曲妥珠單抗,歐洲商品名:Zercepac®,澳大利亞商品名:Tuzucip®和Trastucip®)、漢達遠®(阿達木單抗)和漢貝泰®(貝伐珠單抗)相繼獲批上市,創新產品漢斯狀®(斯魯利單抗)已獲批用於治療微衛星高度不穩定(MSI-H)實體瘤,其鱗狀非小細胞肺癌、廣泛期小細胞肺癌和食管鱗狀細胞癌3項適應症的上市註冊申請也正在審評中。公司亦同步就13個產品、11個免疫聯合治療方案在全球範圍內開展20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。

ASTRUM-005: The first immunotherapy clinical study of SCLC published in JAMA, one of the top medical journals in the world

Shanghai, China, September 27th, 2022 – Shanghai Henlius Biotech, Inc. (2696.HK) announced thatASTRUM-005, an international multi-centre study led by Professor Ying Cheng, has been published in The Journal of the American Medical Association (JAMA, impact factor of 157.3), one of the top four medical journals in the world.ASTRUM-005 trial is a phase 3 study of HANSIZHUANG (serplulimab), an anti-PD-1 monoclonal antibody (mAb) developed by Henlius independently, plus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC). After Prof. Ying Cheng orally presented them at the 2022 ASCO annual meeting, the results of ASTRUM-005 attract wide attention among the global research community. And now, ASTRUM-005 makes its way to the international arena once again, demonstrating the high level of academic acclaim on a global scale, the intelligence of Chinese researchers, and the strength of Chinese pharmaceuticals in terms of independent innovation research and clinical development.

Prof. Ying Cheng, the corresponding author and first author, as well as the leading principal investigator of the study, from Jilin Cancer Hospital, said, 「In the ASTRUM-005 trial, serplulimab combined with chemotherapy achieved by far the longest OS in first-line immunotherapy for ES-SCLC. Compared with chemotherapy, the treatment prolonged median OS by 4.5 months and had the lowest HR of 0.63. In addition, the study showed good safety and consistent efficacy over time. ASTRUM-005 is the first study to demonstrate that PD-1 inhibitors plus chemotherapy can improve survival for patients with ES-SCLC. It is also the first international multi-centre phase 3 clinical study led by Chinese researchers to employ immunotherapy for ES-SCLC treatment, showcasing the expertise and excellence of Chinese researchers. I would like to thank all patients and their families, as well as researchers who contributed to this study. It opens a new chapter in first-line ES-SCLC immunotherapy, which will benefit a large number of patients."

OS 15.4 months, a new record

SCLC is the most aggressive subtype of lung cancer, accounting for around 15% of all lung cancer cases. Both limited stage SCLC (LS-SCLC) and ES-SCLC exhibit high malignancy, strong invasiveness, early metastasis, fast disease progression, and a poor prognosis. The advent of immune checkpoint inhibitors has brought new hope to patients with ES-SCLC. At present, anti-PD-L1 mAbs combined with chemotherapy have been recommended by clinical practice guidelines at home and abroad as the first-line treatment for ES-SCLC. Compared with chemotherapy, the overall survival (OS) of patients with SCLC has been prolonged to a certain extent, but the improvements were still modest, suggesting the need for more effective treatments in this patient population.

ASTRUM-005 is a randomised, double-blind, international, multi-centre, phase 3 clinical study that aims to compare the efficacy and safety of HANSIZHUANG with placebo when combined with chemotherapy in previously untreated patients with ES-SCLC. ASTRUM-005 has set up a total of 128 sites in various countries including China, Turkey, Poland, and Georgia, and enrolled 585 subjects who were screened from 114 sites, among whom 31.5% were White. As of data cutoff for this interim analysis (October 22, 2021), 585 eligible patients were randomised (serplulimab group, n=389; placebo group, n=196), with a Median follow-up duration of 12.3 months.Median OS was significantly longer in the serplulimab group (15.4 months, 95% confidence interval [CI] 13.3-not evaluable) than in the placebo group (10.9 months, 95% CI 10.0-14.3) (hazard ratio [HR] 0.63, 95% CI 0.49-0.82; P <;;0.001).The 24-month OS rate in the two treatment groups were 43.1% and 7.9%, respectively. Median progression-free survival assessed by an independent radiology review committee per RECIST v1.1 was also longer in the serplulimab group compared to the placebo group (5.7 months vs. 4.3 months; HR 0.48, 95% CI 0.38-0.59). Incidence of immune-related adverse events (irAEs) was similar to the approved PD-1/PD-L1 antibodies.

Providing more treatment options for patients worldwide

The success of ASTRUM-005 is a breakthrough in the treatment of ES-SCLC with PD-1 inhibitors. Based on the results of ASTRUM-005, the New Drug Application (NDA) of HANSIZHUANG in combination with chemotherapy for the first-line treatment of ES-SCLC has been accepted by the National Medical Products Administration (NMPA). Furthermore, HANSIZHUANG has been recommended for the first-line treatment of ES-SCLC by the 2022 CSCO Guidelines for Diagnosis and Treatment of SCLC.

In April 2022, the US Food and Drug Administration (FDA) has granted Orphan-Drug Designation (ODD) for HANSIZHUANG for the treatment of SCLC. Based on the positive feedback from FDA Biologics License Application (BLA) submission for HANSIZHUANG for the treatment of ES-SCLC and the discussion on the FDA's Type C consultation meeting, Henlius is planning to soon carry out a bridging study in the US and expected to submit BLA to FDA before Q1 of 2024. At present, there is no anti-PD-1 mAb approved for the first-line treatment of SCLC worldwide. HANSIZHUANG is expected to become the world's first anti-PD-1 mAb for the first-line treatment of SCLC and to fill the clinical gap in the next five years.

Looking forward, Henlius will actively improving efficiency through innovations, focusing on unmet medical needs to bring more high-quality and affordable therapies to patients worldwide.

AboutJAMA

JAMA, published continuously since 1883, is an international peer-reviewed general medical journal aiming to promote the science and art of medicine and the betterment of the public health. JAMA (impact factor of 157.3, one of the highest in medicine and science) is the most widely circulated general medical journal in the world, with more than 290,000 recipients of the print journal, more than 1.6 million recipients of electronic tables of contents and alerts, and over 38 million annual visits to the journal's website. JAMA's reach includes a growing social media presence and vast international news media exposure.

About HANSIZHUANG

HANSIZHUANG (recombinant humanised anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. Up to date, 1 indication is approved for marketing in China, 3 NDAs have been accepted by the NMPA, and 11 clinical trials are ongoing across the world.

HANSIZHUANG was approved by the NMPA for the treatment of MSI-H solid tumours in March 2022 and its synergy with in-house products of the company and innovative therapies are being actively promoted. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 11 clinical trials on immuno-oncology combination therapies in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. As of now, the company has enrolled more than 3,100 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of White is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The NDAs of the first-line treatment for squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC) have been accepted by the NMPA, which makes HANSIZHUANG potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. Furthermore, HANSIZHUANG was recommended by the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer (SCLC) for the treatment of ES-SCLC, and the related clinical trial has also become the first study published in JAMA on SCLC immunotherapy. Serplulimab was also granted orphan drug designation by the FDA for treatment of SCLC.

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, 5 products have been launched in China, 1 approved for marketing in overseas markets, 13 indications approved worldwide, and 5 New Drug Applications (NDAs) accepted for review in China. 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 centers and Shanghai-based manufacturing facilities in line with global Good Manufacturing Practice (GMP), including Xuhui Plant certificated by China and the EU GMP and Songjiang First Plant certificated by China GMP.

Henlius has pro-actively built a diversified and high-quality product pipeline covering over 20 innovative monoclonal antibodies (mAbs) and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as backbone. Apart from the launched products HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab; trade name in Europe: Zercepac®; trade names in Australia: Tuzucip®and Trastucip®), the first China-developed mAb biosimilar approved both in China and Europe, HANDAYUAN (adalimumab) and HANBEITAI (bevacizumab), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumors and its NDA for the treatment of squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC) are under review. What's more, Henlius has conducted over 20 clinical studies for 13 products and 11 combination therapies, expanding its presence in major markets as well as emerging markets.

【參考文獻】

Cheng Y, Han L, Wu L, et al. Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer:The ASTRUM-005 Randomized Clinical Trial.JAMA.2022;328(12):1223–1232. doi:10.1001/jama.2022.16464

*圖片素材來源於JAMA官網

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