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PD-1/PD-L1领域竞争加剧:百时美联手2家日企开发免疫鸡尾酒Opdivo/mogamulizumab

  1. mogamulizumab
  2. Opdivo
  3. PD-1免疫疗法
  4. 百时美施贵宝

来源:生物谷 2014-12-11 16:44

PD-1/PD-L1免疫疗法竞争异常激烈,百时美近日联合小野和协和发酵麒麟,合作开发免疫鸡尾酒疗法Opdivo/mogamulizumab。此前,阿斯利康也与协和发酵麒麟达成合作,开发2种免疫鸡尾酒疗法。

2014年12月11日讯 /生物谷BIOON/ --目前,PD-1/PD-L1免疫疗法竞争异常激烈,该领域的佼佼者默沙东、百时美施贵宝、罗氏、阿斯利康均在火速推进各自的临床项目。继昨日默沙东联手安进合作开发免疫鸡尾酒疗法T-vec/Keytruda,近日百时美施贵宝(BMS)也与日本小野制药(Ono Pharmaceutical)、协和发酵麒麟(Kyowa Hakko Kirin)达成临床试验合作协议,计划开展一项I期临床试验,调查PD-1免疫检查点抑制剂Opdivo(nivolumab)和抗CCR4单抗mogamulizumab组合疗法。该研究将在日本开展,侧重评估Opdivo/mogamulizumab免疫鸡尾酒作为一种潜在的治疗方案,用于治疗晚期或转移性实体瘤的安全性、耐受性和抗肿瘤活性。(相关阅读:癌症疫苗迎来转机:安进与默沙东合作开发癌症免疫鸡尾酒T-vec/Keytruda

Opdivo于2014年9月在日本上市,是全球获批的首个PD-1免疫疗法,首个适应症为晚期黑色素瘤。目前,百时美施贵宝正在全球范围内开展50多个临床试验,评估Opdivo用于多种类型肿瘤的治疗。mogamulizumab于2012年5月在日本上市,用于治疗复发性/难治性CCR4阳性成人T细胞白血病淋巴瘤(ATL),并在2014年3月扩大适应症用于复发性/难治性CCR4阳性外周T细胞淋巴瘤(PTCL)和皮肤T细胞淋巴瘤(CTCL)的治疗。在美国和欧盟,评估mogamulizumab治疗ATL、PTCL、CTCL的相关临床试验正在进行中。

Opdivo和mogamulizumab均属于名为肿瘤免疫疗法的新一类抗癌药物,旨在通过靶向免疫系统中特定的调控元件,利用人体自身的免疫系统攻击肿瘤。Opdivo能够结合至活化T细胞上表达的免疫检查点受体PD-L1,阻断该通路使免疫系统攻击肿瘤。mogamulizumab则可以抑制帮助肿瘤逃逸免疫系统监视的某些免疫细胞。这2种药物各自的临床前证据表明,Opdivo/mogamulizumab免疫鸡尾酒疗法可能能够增强抗肿瘤免疫应答。

百时美施贵宝表示,与小野制药和协和发酵麒麟的合作,将进一步完善Opdivo广泛的临床项目,将推动对Opdivo/mogamulizumab免疫鸡尾酒疗法的了解,同时也是公司致力于开发免疫组合疗法用于转移性癌症患者的一个例子。

该I期研究将由小野制药和协和发酵麒麟开展,进一步的合作细节尚未披露。早在今年7月,百时美已与小野制药达成了一项免疫肿瘤学战略合作,联合开发和商业化PD-1免疫检查点抑制剂Opdivo和CTLA-4免疫检查点抑制剂Yervoy(易普利姆玛),同时开发以Opdivo为基础的组合疗法用于广泛类型的肿瘤。此次合作,将显著提升百时美免疫肿瘤学产品组合在全球范围内的潜在价值,尤其是亚洲地区。另外,阿斯利康今年7月也与协和发酵麒麟达成了战略合作,开发2种免疫鸡尾酒疗法。(相关阅读:百时美与小野制药在亚洲地区达成免疫肿瘤学战略合作阿斯利康与协和发酵麒麟合作开发免疫鸡尾酒疗法

关于PD-1/PD-L1免疫疗法:

癌细胞可利用“调节子(regulator)”途径,如检查点(checkpoint)途径,逃避机体免疫系统的侦察,从而保护肿瘤免受免疫系统的攻击。PD-1/PD-L1免疫疗法是当前备受瞩目的新一类抗癌免疫疗法,旨在利用人体自身的免疫系统抵御癌症,通过阻断PD-1/PD-L1信号通路使癌细胞死亡,具有治疗多种类型肿瘤的潜力,有望实质性改善患者总生存期(OS)。该领域的佼佼者——默沙东、百时美施贵宝、阿斯利康、罗氏均在火速推进各自的临床项目,调查单药疗法和组合疗法用于多种癌症的治疗,以彻底发掘该类药物的最大临床潜力。

此次竞赛中,百时美和默沙东稍微领先。百时美的PD-1抑制剂Opdivo(nivolumab)于今年7月获日本批准,是全球批准的首个PD-1抑制剂;而默沙东的PD-1抑制剂Keytruda(pembrolizumab)于今年9月初获FDA批准,是美国批准的首个PD-1抑制剂;这2种药物获批的首个适应症均为黑色素瘤。阿斯利康和罗氏的PD-L1抑制剂也已处于III期临床。(生物谷Bioon.com)

英文原文:Ono Pharmaceutical, Bristol-Myers Squibb and Kyowa Hakko Kirin Announce Immuno-Oncology Clinical Collaboration Studying Opdivo (nivolumab) and Mogamulizumab in Advanced Solid Tumors

TOKYO & OSAKA, Japan & NEW YORK--(BUSINESS WIRE)--Ono Pharmaceutical Co.,Ltd. (Tokyo: 4528), Bristol-Myers Squibb Company (NYSE:BMY) and Kyowa Hakko Kirin Co., Ltd. (Tokyo: 4151,“Kyowa Hakko Kirin”) announced today the companies have entered into a clinical trial collaboration agreement to conduct a Phase 1 combination study with Opdivo (nivolumab), a PD-1 immune checkpoint inhibitor, and mogamulizumab, an anti-CCR4 antibody. The study, which will be conducted in Japan, will focus on evaluating the safety, tolerability and anti-tumor activity of combining Opdivo and mogamulizumab as a potential treatment option for patients with advanced or metastatic solid tumors.

Opdivo, launched in Japan in September 2014 for the treatment of patients with unresectable melanoma, is being developed in multiple tumor types in more than 50 clinical trials worldwide. Mogamulizumab was launched in Japan in May 2012 for the treatment of relapsed or refractory CCR4-positive Adult T-cell Leukemia-Lymphoma (ATL), and granted the indication expansion in March 2014 for relapsed or refractory CCR4-positive Peripheral T-Cell Lymphoma (PTCL) and Cutaneous T-Cell Lymphoma (CTCL). Clinical trials with mogamulizumab in ATL, PTCL, and CTCL are ongoing in the U.S., European Union (EU) and other countries.

Opdivo and mogamulizumab are part of a new class of cancer treatments known as immunotherapies, which are designed to harness the body’s own immune system in fighting cancer by targeting distinct regulatory components of the immune system. Opdivo binds to the checkpoint receptor PD-1 expressed on activated T-cells, blocking this pathway and enabling the immune system to attack tumors, while mogamulizumab can suppress some of the immune cells that shield the tumor from the immune system. Pre-clinical evidence for each therapy suggests the combination of Opdivo and mogamulizumab may lead to an enhanced anti-tumor immune response compared to either agent alone.

“Studying combination regimens of immunotherapies offers the opportunity to explore the potential of enhanced efficacy compared to current standards of care in treating cancer,” said Hiroshi Awata, Member of the Board of Directors, Vice President Executive Officer/ Executive Director, Clinical Development & Clinical Development Planning, Ono. “We are delighted to be able to pursue the possibility of immunotherapies through this collaboration with Kyowa Hakko Kirin. We believe that there is a strong rationale to explore the combination of Opdivo and mogamulizumab with the goal of identifying a new treatment option for these cancer patients.”

“Our collaboration with Kyowa Hakko Kirin further complements the broad clinical development program for Opdivo, will advance our understanding of the combination of Opdivo and mogamulizumab, and is an example of our commitment to develop combination immuno-oncology regimens for patients with metastatic cancer,” stated Michael Giordano, senior vice president, Head of Development, Oncology, Bristol-Myers Squibb.

“It is exciting for us to build a partnership with Ono and Bristol-Myers Squibb in immuno-oncology,” said Yoichi Sato, Managing Executive Officer, Vice President, Head of Research and Development Division of Kyowa Hakko Kirin. “The planned combination study will help determine whether the combination of these two immunotherapies can deliver better outcomes in patients with advanced cancers.”

The study will be conducted by Ono and Kyowa Hakko Kirin. Additional details of the collaboration were not disclosed.

About Opdivo (nivolumab)

Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. Opdivo is an investigational, human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 expressed on activated T-cells.

Opdivo is being studied across multiple tumor types in more than 50 trials – as monotherapy or in combination with other therapies – in which more than 7,000 patients have been enrolled worldwide. Among these are several potentially registrational trials in non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), head and neck cancer, glioblastoma and non-Hodgkin lymphoma (NHL).

In 2012, the FDA granted Fast Track designation for Opdivo in NSCLC, melanoma and RCC. In April 2014, the company initiated a rolling submission with the FDA for Opdivo in third-line pre-treated squamous cell NSCLC and expects to complete the submission by year-end. The FDA granted Opdivo Breakthrough Therapy Designation in May 2014 for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab. On July 4, Ono Pharmaceutical Co. announced that Opdivo received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma and launched on September 2, making Opdivo the first PD-1 immune checkpoint inhibitor approved and launched anywhere in the world. On September 26, Bristol-Myers Squibb announced that the FDA accepted for priority review the Biologics License Application for previously treated advanced melanoma, and the Prescription Drug User Fee Act goal date for a decision is March 30, 2015. The FDA also granted Opdivo Breakthrough Therapy status for this indication. In the EU, the European Medicines Agency (EMA) has validated for review the Marketing Authorization Application (MAA) for Opdivo in advanced melanoma. The application has also been granted accelerated assessment by the EMA’s Committee for Medicinal Products for Human Use. The EMA also validated for review the MAA for Opdivo in NSCLC.

About Mogamulizumab

Mogamulizumab (Brand name: POTELIGEO®) is a novel, humanized mAb directed against CC chemokine receptor type 4 (CCR4). Engineered by Kyowa Hakko Kirin's unique POTELLIGENT® Technology, the antibody is designed to kill its target cells through potent antibody-dependent cellular cytotoxicity. Mogamulizumab was launched in Japan in May 2012 for the treatment of patients with relapsed or refractory CCR4-positive adult T-cell leukemia-lymphoma (ATL). The drug was approved for indication expansion and was granted marketing authorization in Japan for the treatment of patients with relapsed or refractory CCR4-positive, peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) in March 2014. Clinical trials with mogamulizumab in ATL, PTCL, and CTCL are ongoing in the US, EU and other countries.

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