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百时美施贵宝与Incyte合作开发nivolumab/INCB24360免疫组合疗法

  1. INCB24360
  2. Incyte
  3. nivolumab
  4. 免疫疗法
  5. 百时美施贵宝

来源:生物谷 2014-05-28 10:10

百时美施贵宝与Incyte达成临床开发合作,调查免疫组合疗法nivolumab+INCB24360用于多种癌症的治疗。这2种药物均属于新一类的免疫疗法,利用人体自身的免疫系统对抗癌症。

2014年5月27日讯 /生物谷BIOON/ --百时美施贵宝(BMS)与Incyte公司5月27日联合宣布,双方已签署一项临床合作协议,在一项I/II期研究中,评估实验性单抗nivolumab+INCB24360组合疗法的安全性、耐受性及初步疗效。该项研究将涉及多种类型的肿瘤,可能包括黑色素瘤、非小细胞肺癌(NSLCL)、卵巢癌、结直肠癌(CRC)、头颈部鳞状细胞癌(SCCHN)和弥漫性大B细胞淋巴癌(DLBCL)。该项研究预计将于2014年第四季度开始。进一步的合作细节尚未披露。

nivolumab是一种实验性PD-1免疫检查点抑制剂,INCB24360则是一种口服吲哚胺双加氧酶-1(IDO-1)抑制剂。这2者均属于新一类的免疫疗法,旨在利用机体自身的免疫系统对抗癌症。

nivolumab和INCB24360靶向免疫系统中不同的调控元件。临床前证据显示,与任一单药疗法相比,2者组合疗法可能会带来更强的抗肿瘤免疫应答。

关于Nivolumab(BMS-936559):

癌细胞可能利用“监管(regulatory)”途径,如检查点(checkpoint)途径,逃避机体免疫系统,保护肿瘤免受免疫攻击。

Nivolumab是一种实验性、全人源化IgG4、抗程序性死亡受体1(PD-1)单克隆抗体,能够抑制PD-1与程序性死亡配体1(PD-L1/B7-H1)和程序性死亡配体2(PD-L2/B7-DC)的结合。阻断PD-1与其配体的相互作用,可能使T细胞恢复抗肿瘤免疫应答。目前,百时美施贵宝正调查nivolumab用于恶性黑色素瘤、肾癌、非小细胞肺癌及其他癌症的治疗。

nivolumab的开发项目研究总数超过25个:调查作为单药疗法或与其他药物联合用药,用于多个肿瘤类型的治疗,包括:非小细胞肺癌、小细胞肺癌、黑色素瘤、肾细胞癌、肝癌、血液癌症、三阴性乳腺癌、胃癌、胰腺癌。FDA于2013年授予nivolumab治疗黑色素瘤、肾细胞癌和非小细胞肺癌的快速通道地位。

关于INCB24360:

INCB24360是一种口服生物可利用的吲哚胺双加氧酶-1(IDO-1)小分子抑制剂,在生化和细胞试验中具有纳摩尔级药性,在体外试验中能够强劲提高T淋巴细胞、树突状细胞和自然杀死细胞反应。在小鼠模型中,该药作为单药疗法及组合疗法,已显示出对癌症的疗效。

目前,该药处于转移性黑色素瘤I/II期临床开发,以及作为单药疗法用于卵巢癌的治疗。

此外,Incyte也已与默沙东达成临床合作,将INCB24360与默沙东PD-1免疫检查点抑制剂联合用于非小细胞肺癌的治疗。

英文原文:Bristol-Myers Squibb and Incyte Enter Clinical Collaboration Agreement to Evaluate Combination Regimen of Two Novel Immunotherapies

Phase I/II study to evaluate nivolumab, Bristol-Myers Squibb’s investigational PD-1 immune checkpoint inhibitor with Incyte’s investigational oral IDO1 inhibitor for multiple cancers

NEW YORK & WILMINGTON, Del.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) and Incyte Corporation (Nasdaq:INCY) announced today the establishment of a clinical trial collaboration to evaluate the safety, tolerability and preliminary efficacy of a combination regimen of Bristol-Myers Squibb’s investigational PD-1 immune checkpoint inhibitor, nivolumab, and Incyte’s oral indoleamine dioxygenase-1 (IDO1) inhibitor, INCB24360, in a Phase I/II study. Multiple tumor types will be explored in the study, which could potentially include melanoma, non-small cell lung (NSCLC), ovarian, colorectal (CRC), squamous cell carcinoma of the head and neck (SCCHN) and diffuse large B-cell lymphoma (DLBCL).

Nivolumab and INCB24360 are part of a new class of cancer treatments known as immunotherapies that are designed to harness the body’s own immune system in fighting cancer. Nivolumab and INCB24360 target distinct regulatory components of the immune system, and there is preclinical evidence suggesting that the combination of these two agents may lead to an enhanced anti-tumor immune response compared to either agent alone.

“Bristol-Myers Squibb is committed to pursuing the full potential of its immuno-oncology portfolio through the study of promising approaches to combination regimens,” stated Michael Giordano, senior vice president, Oncology and Immunosciences Development. “Given the encouraging data for Incyte’s IDO1 inhibitor and our current understanding of nivolumab’s anti-tumor immune response, we see this as an important area of study to add to our broad clinical development program.”

“The field of immunotherapy has the potential to transform the treatment of many cancers and significantly improve patient outcomes,” stated Hervé Hoppenot, President and Chief Executive Officer of Incyte. “Given the synergistic activity we have seen with our IDO1 inhibitor when combined with checkpoint inhibitors in preclinical models, and based on our emerging clinical data, we look forward to collaborating with Bristol-Myers Squibb to explore this combination across a wide range of tumor types.”

The study, which is expected to begin in the fourth quarter of 2014, will be co-funded by the companies and conducted by Incyte. Additional details of the collaboration were not disclosed.

About Nivolumab

Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. Nivolumab is an investigational, fully-human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells. By blocking this pathway, nivolumab can enable the immune system to resume its ability to recognize, attack and destroy cancer cells.

Bristol-Myers Squibb has a broad, global development program in place to study nivolumab in multiple tumor types consisting of more than 35 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 NSCLC, melanoma and renal cell carcinoma. In 2013, the FDA granted Fast Track designation for nivolumab in these three tumor types.

About INCB24360

INCB24360 is an orally bioavailable small molecule inhibitor of IDO1 that has nanomolar potency in both biochemical and cellular assays, potent activity in enhancing T lymphocyte, dendritic cell and natural killer cell responses in vitro, with a high degree of selectivity. INCB24360 has been shown to be efficacious in mouse models of cancer as a single agent and in combination with cytotoxic and immunotherapy agents, and its ability to reduce tumor growth is dependent on a functional immune system – consistent with its proposed mechanism of action. A Phase I dose-escalation trial demonstrated that INCB24360 results in greater than 90 percent inhibition of IDO1 activity at generally well-tolerated doses.

INCB24360 is currently in Phase I/II development for metastatic melanoma in combination with ipilimumab (www.clinicaltrials.gov Identifier: NCT01604889) and as monotherapy for ovarian cancer (www.clinicaltrials.gov Identifier: NCT01685255). Incyte has also established a clinical agreement with Merck to combine INCB24360 with Merck’s novel anti-PD-1 immunotherapy checkpoint inhibitor in a non-small cell lung cancer study.

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