免疫检查点抑制剂Immune Checkpoint inhibitor

ONO Files for Regulatory Approval of “Nivolumab (ONO-4538/BMS-936558)” for Treatment of Malignant Melanoma

Ono Pharmaceutical Co., Ltd. (Head Office: Osaka City; President and Representative Director: Gyo Sagara;”ONO”) announced today that ONO filed an application to obtain a manufacturing and marketing approval for fully-human IgG4 PD-1 immune checkpoint inhibitor “Nivolumab (ONO- 4538/BMS-936558)” for treatment of malignant melanoma.

Malignant melanoma is considered to be a tumor which develops through malignant transformation of pigment-producing skin cells. In Japan, the prognosis of patients with unresectable malignant melanoma is extremely poor and there is no drug therapy that improves the prognosis significantly ,
the development of a new drug for the disease has been required. Nivolumab is a fully-human lgG4 PD-1 immune checkpoint inhibitor. PD-1 is one of the receptors expressed on activated lymphocytes, and is involved in a negative regulatory system to suppress the activated lymphocytes (a negative signal). It has been reported that tumor cells utilize this system to escape from the host immune responses.

Nivolumab is expected to have anti-tumor activity by blocking the interaction of PD-1 with its ligands (PD-L1 and PD-L2), preventing the negative regulatory signal mediated by the receptor (PD-1)-ligand interaction and thereby promoting the host immune response in which tumor cells and viruses are recognized as foreign and eliminated. Nivolumab was designated as an orphan drug indicated for malignant melanoma by Ministry of Health, Labour and Welfare on June 17, 2013.

Nivolumab is a fully-human lgG4 PD-1 immune checkpoint inhibitor generated under a research collaboration agreement entered into in May 2005 between ONO and Medarex, Inc. When Medarex, Inc. was acquired by Bristol-Myers Squibb Company (“BMY”) in 2009, BMY succeeded the rights to
develop and commercialize Nivolumab in North America.

Under a strategic license agreement enterd into in September 2011 between ONO and BMY, ONO granted BMY exclusive rights to develop and commercialize Nivolumab in the rest of the world, except in Japan, Korea and Taiwan where ONO retained all the rights to develop and commercialize
Nivolumab. “Nivolumab is an antibody drug with a new mechanism of action, which is expected to have efficacy in several cancers including malignant melanoma, non-small-cell lung cancer, and renal cell carcinoma,” said Gyo Sagara, the President and Representative Director of ONO. “We are happy to
submit a manufacturing and marketing approval for Nivolumab as a drug targeting the PD-1 pathway for the first time in the world. “

http://www.ono.co.jp/eng/news/pdf/sm_cn131224.pdf

哎，后面好要越来越多{:soso_e109:}

几个新开的临床


MPDL3280A + 特罗凯
A Study of the Safety and Pharmacology of Combined MPDL3280A and Tarceva Treatment in Patients With Non-Small Cell Lung Cancer
http://clinicaltrials.gov/ct2/show/NCT02013219



MK-3475 + Pazopanib
Merck Collaborates with GlaxoSmithKline to Evaluate Novel Combination Regimen for Advanced Renal Cell Carcinoma

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the initiation of a clinical trial to evaluate the combination of the company’s investigational anti-PD-1 immunotherapy, MK-3475, and GlaxoSmithKline’s orally administered kinase inhibitor, pazopanib, in advanced renal cell carcinoma.

“Collaborations like this are central to Merck’s strategy to evaluate the potential of MK-3475 for the treatment of cancer,” said Iain Dukes, senior vice president, Licensing and External Scientific Affairs, Merck Research Laboratories. “We look forward to initiating further collaborations to investigate MK-3475 in combination with other anti-cancer agents across a range of tumor types.”

Merck and GlaxoSmithKline entered a collaboration to study MK-3475 with pazopanib and other agents in the GlaxoSmithKline portfolio in the future. This Phase I/II clinical trial is designed to evaluate the safety and efficacy of a combination of MK-3475 and pazopanib in treatment naïve patients with advanced renal cell carcinoma. Further details of the collaboration were not disclosed.
http://www.mercknewsroom.com/new ... luate-novel-combina

0 mg/10 mL (5 mg/mL)（7200美元）和200 mg/40 mL (5 mg/mL)(28800美元)。
对于100kg的病人，一个周期价格是43200美元，四个周期是172800美元

Cancer immunotherapy comes of age

Ira Mellman, George Coukos & Glenn Dranoff

Activating the immune system for therapeutic benefit in cancer has long been a goal in immunology and oncology. After decades of disappointment, the tide has finally changed due to the success of recent proof-of-concept clinical trials. Most notable has been the ability of the anti-CTLA4 antibody, ipilimumab, to achieve a significant increase in survival for patients with metastatic melanoma, for which conventional therapies have failed. In the context of advances in the understanding of how tolerance, immunity and immunosuppression regulate antitumour immune responses together with the advent of targeted therapies, these successes suggest that active immunotherapy represents a path to obtain a durable and long-lasting response in cancer patients.

nature10673.pdf (590.42 KB, 下载次数: 38)

2014-1-7 10:06 上传

点击文件名下载附件

OncologyMeetsImmunology:TheCancer-ImmunityCycle

Daniel S. Chen and Ira Mellman

The genetic and cellular alterations that define cancer provide the immune system with the means to generate T cell responses that recognize and eradicate cancer cells. However, elimination of cancer by T cells is only one step in the Cancer-Immunity Cycle, which manages the delicate balance between the recognition of nonself and the prevention of autoimmunity. Identification of cancer cell T cell inhibitory signals, including PD-L1, has prompted the development of a new class of cancer immunotherapy that specifically hinders immune effector inhibition, reinvigorating and potentially expanding preexisting anticancer immune responses. The presence of suppressive factors in the tumor microenvironment may explain the limited activity observed with previous immune-based therapies and why these therapies may be more effective in combination with agents that target other steps of the cycle. Emerging clinical data suggest that cancer immunotherapy is likely to become a key part of the clinical management of cancer.

Chen and Mellman Review.pdf (1.7 MB, 下载次数: 41)

2014-1-7 10:09 上传

点击文件名下载附件

求论坛找个翻译吧,

贵不过命，哎，

希望早日能普及，价格惠民。

BMS的936558对化疗的III期临床即将开始

An Open-Label, Randomized, Phase 3 Trial of Nivolumab Versus Investigator's Choice Chemotherapy as First-Line Therapy for Stage IV or Recurrent PD-L1+ Non-Small Cell Lung Cancer (CheckMate 026)

http://clinicaltrials.gov/ct2/show/NCT02041533

MRK先下手的针对PD-1+患者的I期临床：

Study of MK-3475 in Participants With Advanced Non-small Cell Lung Cancer (MK-3475-025)

http://clinicaltrials.gov/ct2/show/NCT02007070