肿瘤免疫治疗：三十年磨一剑

《科学》杂志将肿瘤免疫治疗列为2013年十大科学突破的首位。有关肿瘤免疫治疗的临床试验进展、企业合作、并购、融资的新闻层出不穷。CTLA-4、PD-1、PD-L1这些热门靶点也频繁被业界媒体提及。


其实，肿瘤免疫治疗从1891年纽约一名外科医生William Coley用细菌来治疗肿瘤的试验开始，经历了漫长的探索，遭遇重大挫折。直到1984年，美国国立癌症研究院史蒂夫•罗森伯格(Steve Rosenberg)团队成功地用高剂量白细胞介素2(IL-2)治愈第一例病人，给肿瘤免疫治疗带来一线曙光。此后，新技术新治疗方案包括单克隆抗体、肿瘤疫苗不断涌现，虽然对一些病人和适应症有效，但没能被大规模应用。30年后，让这个领域扬眉吐气的是两类治疗途径：一种是针对免疫检验点的抗体;另一种是表达嵌合抗原受体的自体T细胞疗法。

免疫检验点抗体是通过激活病人自身免疫系统中的T细胞来消灭肿瘤细胞(见图1：免疫检验点共信号机制和图2：免疫检验点抗体作用机理)。CTLA-4单抗Ipilimumab是唯一被批准上市的免疫检验点抑制剂。该抗体由Medarex公司发现，授权百时美施贵宝开发，在恶性黑色素肿瘤患者上取得显著生存获益，于2011年在美国批准上市。另一个CTLA-4单抗tremelimumab也是由Medarex公司发现，经辉瑞开发，又转让给阿斯利康继续开发。针对PD-1和PD-L1的单抗有多家公司开发，竞争十分激烈。目前，在后期临床试验的有nivolumab(PD-1)、lambrolizumab(PD-1)和MPDL3280A(PD-L1)。其他针对OX40、4-1BB的多个单抗在早期开发中。与此同时，CTLA-4和PD-1单抗的联合治疗试验也在进行，并取得阶段性成果。过去3年，ASCO(美国临床肿瘤协会)年会上，免疫检验点抑制剂单抗临床试验数据发布都是令人瞩目的亮点。预计今后几年内会有多个免疫检验点抗体上市，适应症也会扩充到其他肿瘤类型。

图1 免疫检验点共信号机制



T细胞的激活依靠“双信号”细致地调控。一个激活信号是MHC（主要组织相容性复合体）-TCR（T细胞受体）的结合。另一个来自共刺激分子（OX40，4-1BB）和共抑制分子（CTLA-4.PD-L1.PD-1）的信号传递，好比是汽车的“油门”或“刹车”。

图2 免疫检验点抗体作用机理





肿瘤细胞入侵后，会压制T-细胞激活，从而逃脱免疫系统的围剿。如果我们能用针对OX40、4-1BB的激活剂单抗来“猛踩油门”，或针对CTLA-4、PD-1/PD-L1的拮抗剂单抗来“松开刹车”，T细胞都可以摆脱肿瘤细胞的压制，重新被激活来识别杀伤肿瘤细胞。

研发领域跌宕起伏

嵌合抗原受体T细胞疗法(CAR)是运用病人自体T细胞的个性化治疗方法。其临床试验由几个美国研究机构主导。根据这些试验结果，CAR在其他治疗方法无效的淋巴癌患者身上有效率很高。对部分病人，血液肿瘤在几天内溶解消失。当然，CAR制备过程的复杂性对临床试验的规模是一个限制，所以现在病例数与免疫检验点抗体相比要少很多，且主要局限于表达CD19抗原的肿瘤(见图3：嵌合抗原受体CAR自体T细胞疗法)。

图3 嵌合抗原受体CAR自体T细胞疗法



嵌合抗原受体（CAR）是一种个性化的治疗方法。病人的T细胞通过基因工程修饰，加上一个嵌合蛋白。经过嵌合蛋白修饰的T细胞仿佛带上了一个“向导”，能像巡航导弹一样，识别攻击带有CD19抗原的肿瘤细胞并引发免疫反应。

肿瘤免疫疗法是一个广大领域。除了免疫检验点抗体、CAR捷报频传之外，还有其他途径，比如肿瘤疫苗。2010年美国批准上市的Sipuleucel-T是一种针对前列腺癌的自体树突状细胞疫苗，也是第一个被批准上市的治疗性肿瘤疫苗。这个产品在上市时给业界带来很高期望。可惜在市场上表现差强人意。2014年3月17日，溶瘤病毒疫苗OncoVex在恶性黑色素瘤患者的Ⅲ期试验阶段性结果公布，数据不错。3天之后，MAGE-A3抗原疫苗的针对非小细胞肺癌的大型Ⅲ期试验没有到达预期效果。4月4日，OncoVex Ⅲ期试验的正式结果公布，达到了主要终点，但次要终点OS总生存期没有达到，可谓一波三折。这种跌宕起伏充分反映了我们对肿瘤疫苗分子细胞水平上机制的了解依然十分有限，该领域潜力和研发风险巨大，对以后的肿瘤疫苗研发有很多启发。

革命性医药技术的发展往往是一个在黑暗中摸索的过程，需要科学家持续的努力和不断的调整，输赢不在起跑线上。以CTLA-4单抗为例，tremelimumab的临床试验与ipilimumab并驾齐驱，本来有机会成为第一个被批准的免疫检验点抗体，但可惜因多种因素，一线治疗的Ⅲ期试验意外提前中止。Ipilimumab后来居上，是汲取了tremelimumab的教训，在临床试验方案上作了改进。

CAR技术自1989年起，经过三代演进：第一代只有T细胞刺激因子，没有共刺激因子；第二代只有单个共刺激因子;第三代才有两个共刺激因子。这些改进都是基于一系列临床试验，对CAR的有效性有显著提高。（如下图所示）

图4 嵌合抗原受体CAR的演化



三代CAR技术的演化反映了共刺激分子的重要作用

从更宏观的角度来看，CAR是肿瘤过继细胞转移治疗的一种。其他的疗法还有肿瘤浸润性淋巴细胞(TIL)和T细胞受体(TCR)等等。这些疗法都在早期试验阶段，尚有大量未知因素。CAR的成功是免疫学家集思广益，不断试错的结晶。

中国古人说：“失败是成功之母”，用在肿瘤免疫的案例上是再恰当不过了。

试验设计的思维框架

肿瘤免疫治疗不但对一部分病人疗效显著，而且对该类新药临床试验方案设计与安全性评估都带来新的范式(Paradigm)和思维框架。

首先，传统的临床试验终点依赖在不同药剂量下对肿瘤大小的评估，假设肿瘤体积的变化趋势是单一的。在免疫检验点单抗的临床试验中，有一部分病人的肿瘤体积在前几个月会变大，药物的疗效要几个月后才能逐渐显现，然后肿瘤体积再逐渐变小，得到控制。所以该类新药的临床试验方案设计需要考虑到这些新的变数，以最优化的疗程、终点与统计学方法来测试新药的疗效。

其次，在免疫检验点单抗的临床试验中，应答率并不高。但对小部分有疗效的病人，药物的作用往往可以持续一年到几年的时间。在ipilimumab的长期试验中，1861个黑色素瘤病人中，22%存活3年，17%存活7年或更长时间。这与肿瘤小分子靶向药物有不少区别。在宾州大学CAR的首次临床试验中只有3个病人，都有疗效，两个病人症状完全缓解。

一个很关键的、悬而未解的问题，是怎样运用生物标记物依照个性化医疗的原理来挑选最合适接受肿瘤免疫治疗的病人。这是我从事转化科学研究的同事和同行们都很关注的。

最后，肿瘤免疫治疗虽然避免了一些传统肿瘤药物的毒性，但带来新的安全性的挑战。CAR会引起急性不良反应(包括发烧、低血压和极度疲乏)。免疫检验点单抗也可能引起自身免疫系统相关的严重不良反应(例如大肠炎和下垂体炎等)，甚至死亡。

2014年4月9日，纪念斯隆-凯特琳癌症中心基于安全性原因，暂停了一个CAR临床试验的病人入组。时值美国肿瘤研究协会AACR年会期间，这个决定引起了业界高度关注。怎样理解这些不良反应的成因并制订相应的安全性评价标准与临床试验方案也是业界的当务之急。


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高盛：肿瘤免疫药物上市时间及市场份额预测

放大字体  缩小字体 发布日期：2014-06-04  来源：高盛  浏览次数：574
【新药汇www.xinyaohui.com讯】 肿瘤免疫药物的临床数据在2014ASCO年会上轮番轰炸眼球，高盛基于已知数据对暂时处于领先地位的4个anti-PD-1/PD-L1药物在黑色素瘤、NSCLC和肾细胞癌等适应症上的上市时间表进行了预测，具体时间如下：

预计上市
药物
方案
适应症
2014年底
MK-3475
二线
Yervoy治疗后复发黑色素瘤




2015年中
nivolumab
三线
鳞状NSCLC
2015下半年
nivolumab
二线
鳞状NSCLC
2015下半年
nivolumab
二线
非鳞状NSCLC




2016上半年
MK-3475
二线
转移性黑色素瘤
2016年中
nivolumab
一线/二线
转移性黑色素瘤
2016年中
MK-3475

PD-L1阳性 NSCLC
2016下半年
nivolumab
二线
肾细胞癌
2016年底
MPDL3280A
二线/三线
NSCLC
2016年底
MEDI4736
三线
PD-L1阳性 NSCLC




2017年中
nivolumab+Yervoy

黑色素瘤
2017年底
MPDL3280A+ Avastin
一线
肾细胞癌




2018上半年
nivolumab+Yervoy

肾细胞癌
2018上半年
nivolumab+Yervoy

NSCLC
2018上半年
MEDI4736
二线
III期NSCLC

在高盛看来，2015年对于BMS异常关键，nivolumab将在NSCLC这个适应症上寻求全方位突破，阿斯利康的MEDI4736和罗氏的MPDL3280A可能最早也要等到2016年才会上市，不过这两家公司如果发布其他重磅数据，这两个药物的上市进程则有可能被加快。
根据Bloomberg的预测，目前推进最快的5个肿瘤免疫药物（Yervoy已获批用于治疗黑色素瘤）在2020年的销售额将达到130亿美元，其中BMS的anti-PD-1单抗nivolumab将达到46亿美元，再加上Yervoy(ipilimumab)的26亿美元，BMS将成为肿瘤免疫药物市场的最大赢家。默沙东1月13日启动了MK-3475的滚动新药申请程序，FDA在5月6日正式受理了MK-3475的BLA，进入加速审批通道后的预定审批期限是10月28日。MK-3475极有可能成为首个获批上市的靶向PD-1的免疫检查点（immune checkpoint）调节药物。Bloomberg预测2020年MK-3475会占据肿瘤免疫药物市场第2大的份额，达到33亿美元。

百时美施贵宝nivolumab+Yervoy组合疗法Ib期1年总生存率高达94%
来源：生物谷 2014-06-04 08:59


2014年6月4日讯 /生物谷BIOON/ --百时美施贵宝（BMS）6月2日公布了一项多组Ib期剂量范围试验Study-004的随访数据。该研究在晚期黑色素瘤患者中开展，调查了实验性PD-1免疫检查点抑制剂nivolumab和黑色素瘤药物Yervoy（ipilimumab）同时给药或先后给药的安全性和疗效。对nivolumab（1mg/kg）+Yervoy（3mg/kg）同时给药组的随访数据表明，该治疗组患者一年总生存率（OS）达94%，两年总生存率达88%。这一剂量方案已用于正在开展的II期和III期临床试验。同时给药组中，未出现新的安全性信号。相关数据已提交至美国临床肿瘤学会（ASCO）第50届年会上。

关于Nivolumab（BMS-936559）:

癌细胞可能利用“调节子（regulator）”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。

关于Yervoy：

Yervoy是一种重组人单克隆抗体，阻断细胞毒性T淋巴细胞相关抗原4（CTLA-4）。CTLA-4是一种T细胞活化的负调控因子，Yervoy与CTLA-4结合后，能阻断CTLA-4与其配体CD80/CD86的相互作用。阻断CTLA-4已被证明能够增强T细胞的活化和增殖。Yervoy在黑色素瘤患者中的疗效作用机制，是间接通过T细胞介导的抗肿瘤免疫反应。FDA于2011年3月批准Yervoy 3mg/kg单药疗法用于不能手术切除或转移性黑色素瘤患者的治疗，目前该药已获全球40多个国家批准。（生物谷Bioon.com）

英文原文：One- & Two-Year Survival Rates of 94% and 88% Announced from Phase 1b Trial of Investigational PD-1 Checkpoint Inhibitor Nivolumab and Yervoy® (ipilimumab) in Advanced Melanoma; Ongoing Phase 2/3 Trials to Confirm Results

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) today announced follow up results from Study -004, a multi-arm Phase 1b dose-ranging trial evaluating the safety and activity of the combination regimen of nivolumab, an investigational PD-1 immune checkpoint inhibitor, and Yervoy® (ipilimumab) given either concurrently or sequentially in patients with advanced melanoma (n=127). After an additional year of follow up of the cohort that received the concurrent combination regimen of nivolumab 1 mg/kg plus Yervoy 3mg/kg (n=17), the one-year overall survival (OS) rate was 94% and the two-year OS rate was 88%. These are the doses used in the ongoing Phase 2 and Phase 3 trials, CheckMate -069 and -067. No new safety signals were reported in the concurrent combination cohorts with additional follow up (n=53) and grade 3-4 treatment-related adverse events (AEs) occurred in 62% of patients. The most common were asymptomatic increases in lipase (15%), ALT (12%) and AST (11%). These data will be presented today at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) and featured during an ASCO press briefing at 8 a.m. CDT (Abstract # LBA9003).

“The treatment of advanced melanoma has changed dramatically in the last few years, but there continues to be a need to increase the number of patients who experience a long-term survival benefit,” said Dr. Mario Sznol, Yale University School of Medicine and Yale Cancer Center, presenter of the results. “While these are Phase 1b data, the duration of response and one- and two-year survival rates observed with the combination regimen of nivolumab and Yervoy are very encouraging and support the rationale for the ongoing, late stage trials of this combination regimen.”

“The science of immuno-oncology – harnessing the patient’s immune system to treat cancer – is rapidly evolving,” said Michael Giordano, senior vice president, Head of Development, Oncology & Immunology at Bristol-Myers Squibb. “These results are the most advanced data set to date evaluating the potential of combining immune checkpoint inhibitors. As leaders in the field, they reinforce our aspiration that combining immunotherapies may be foundational and may have the potential to change the standard of care by transforming survival expectations.”

Results from Phase 1b Combination Regimen (Study -004)

Study 004 is a dose-ranging Phase 1 study (n=127) evaluating the safety, antitumor activity and pharmacokinetics of the combination regimen of nivolumab and Yervoy given concurrently or sequentially in patients with advanced melanoma. Prior to enrollment, patients could have received up to three systemic therapies.

In the concurrent regimen cohort (n=53), eligible patients received nivolumab and Yervoy every three weeks for four doses, followed by nivolumab alone every three weeks for four doses. This concurrent combination regimen treatment was subsequently continued every 12 weeks for up to eight doses. Cohorts of a maximum of 17 patients per dose level were enrolled (nivolumab 0.3 mg/kg + Yervoy 3 mg/kg [n=14]; nivolumab 1 mg/kg + Yervoy 3 mg/kg [n=17]; nivolumab 3 mg/kg + Yervoy at an investigational dose of 1 mg/kg [n=16]; nivolumab 3 mg/kg + Yervoy 3 mg/kg [n=6]). In an expansion cohort (n=41), eligible patients received the concurrent combination regimen of nivolumab 1 mg/kg and Yervoy 3 mg/kg every three weeks for four doses, followed by nivolumab alone at 3 mg/kg every two weeks until progression, which is the same schedule utilized in the ongoing Phase 2 and Phase 3 trials. In the sequenced regimen cohort (n=33), patients previously treated with Yervoy received nivolumab alone at 1 mg/kg or 3 mg/kg every two weeks.

Results from this trial were first published in the New England Journal of Medicine and presented at ASCO in 2013. The updated data, including those shown below, are based on a median follow up of 22 months and reflect an additional year of follow up from patients initially enrolled in the trial.

Efficacy Summary: Concurrent and Sequenced Cohorts

Nivolumab (mg/kg) + Yervoy (mg/kg) [n]     ORR, %     CR, %     1-Year OS, %     2-Year OS, %
Concurrent Cohorts [53]     42     17     85     79
0.3 + 3 [14]     21     14     57     50
1 + 3 [17]     53     18     94     88
3 + 1 [16]     44     25     94     NC
3 + 3 [6]     50     0     100     NC
Expansion 1 + 3 [41]     43     10**     NC     NC
Sequenced Cohort [33]     31     3     70 [23]     NC
NC: Not calculated/insufficient follow up; ORR: objective response rate; CR: complete response
**Two unconfirmed responses

Responses were observed regardless of BRAF mutational status or PD-L1 expression.

No new safety signals were reported with additional follow up. Grade 3-4 treatment-related AEs occurred in 62% of patients in the concurrent cohorts, managed with standard algorithms. The most common were asymptomatic increases in lipase (15%), ALT (12%) and AST (11%). Twenty-two patients (23%) discontinued treatment due to related AEs. There was one drug-related death due to fatal multi-organ failure following an initial event of colitis.

About Advanced Melanoma

Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease, and occurs when cancer spreads beyond the surface of the skin to other organs, such as the lymph nodes, lungs, brain or other areas of the body. The incidence of melanoma has been increasing for at least 30 years. In 2012, an estimated 232,130 melanoma cases were diagnosed globally. Melanoma is mostly curable when treated in its early stages. However, in its late stages, the average survival rate has historically been just six months with a one-year mortality rate of 75%, making it one of the most aggressive forms of cancer.

About Bristol-Myers Squibb Immuno-Oncology Trials in Melanoma

Bristol-Myers Squibb is committed to the research and development of immuno-oncology as an innovative approach to treating melanoma and has a broad development program evaluating its approved and investigational immunotherapies – either as single agents or as part of a regimen - across lines of therapy, stages of disease and biomarker expression. Among these are five Phase 3 trials. There are two ongoing Phase 3 trials evaluating nivolumab as a single agent at the 3 mg/kg dose in treatment-naïve patients (CheckMate -066) as well as in patients who have been previously treated (CheckMate -037). A Phase 3 trial evaluating Yervoy 3 mg/kg vs. Yervoy 10 mg/mg in patients with previously treated or treatment-naïve metastatic melanoma is ongoing (Study -169) and the first results of a Phase 3 trial evaluating the investigational use of Yervoy 10 mg/kg in patients with Stage 3 melanoma who are at high risk of recurrence following complete surgical resection (Study -029) will be featured today during an ASCO press briefing at 8 a.m. CDT and presented in an oral session at 3 p.m. CDT (Abstract #LBA9008). Additionally, a Phase 3 trial evaluating the combination regimen of nivolumab and Yervoy in treatment-naïve patients is ongoing (CheckMate -067).

About Nivolumab and Yervoy

Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. Nivolumab and Yervoy are both monoclonal antibodies and immune checkpoint inhibitors, but target different receptors for distinct T-cell checkpoint pathways.

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. We are investigating whether by blocking this pathway, nivolumab would enable the immune system to resume its ability to recognize, attack and destroy cancer cells.

Bristol-Myers Squibb has a broad, global development program 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 non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), head and neck cancer, glioblastoma and non-Hodgkin lymphoma. In 2013, the FDA granted Fast Track designation for nivolumab in NSCLC, melanoma and RCC. Earlier this month, the FDA granted nivolumab Breakthrough Therapy Designation for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab.

Yervoy, which is a recombinant, human monoclonal antibody, blocks the cytotoxic T- lymphocyte antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation. Ipilimumab binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of ipilimumab’s effect in patients with melanoma is indirect through T-cell mediated anti-tumor immune responses. On March 25, 2011, the FDA approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is now approved in more than 40 countries.

YERVOY® (ipilimumab) INDICATION & IMPORTANT SAFETY INFORMATION

YERVOY (ipilimumab) is indicated for the treatment of unresectable or metastatic melanoma.

Nektar新型抗癌药临床前研究结果显著
来源：生物谷 2014-06-06 11:07
2014年6月6日讯 /生物谷BIOON/ --最近旧金山的生物技术公司Nektar公司表示公司开发的新型抗癌药NKTR－214能够明显抑制恶性肿瘤的生长并对多种恶性肿瘤都有疗效。这种药物主要是通过激活IL－2受体复合物来激活患者自身免疫系统以达到清除肿瘤细胞的效果。同时，研究人员还在乳腺癌模型EMT6以及大肠癌模型CT26上检验了NKTR－214与其他免疫药物如抗PD-1药物以及抗CTLA-4药物联合使用的疗效。结果表明联合治疗相对于单独使用抗PD－1或抗CTLA－4类药物有明显改善。例如在EMT6模型中，只使用抗CTLA－4类药物或抗PD－1药物对肿瘤的抑制率进位23％，而联合用药的抑制率则达到了74％。这一研究结果被公布在本月一号在芝加哥举办的全美肿瘤学会年会上。（生物谷Bioon.com）

详细英文报道：

In a preclinical study, San Francisco-based Nektar Therapeutics ($NKTR) found that its investigational cancer drug, NKTR-214, inhibited growth in highly aggressive tumors, showing potential to treat a variety of cancers.

The investigational cancer immunotherapy selectively activates the IL-2 receptor complex to stimulate the patient's own immune system to kill tumor cells. The drug is being developed as a potential treatment for multiple cancers.

"This ability to exploit complementary pathways in the immune system by combining NKTR-214, a new immune activator, with an effective checkpoint inhibitor, such as anti-CTLA-4 or anti-PD-1, holds promise for durable responses in patients," said Stephen Doberstein, senior vice president and chief scientific officer of Nektar Therapeutics, in a statement.

Using preclinical models of breast tumors--EMT6--and colon tumors--CT26--Nektar researchers tested NKTR-214 on its own as well as NKTR-214 in combination with checkpoint inhibitors, either an anti-PD-1 therapy or an anti-CTLA-4 therapy. The studies also compared NKTR-214 single-agent and combination-dosing regimens with single-agent and combination-dosing regimens of anti-PD-1 and anti-CTLA-4 therapies.

In both the breast and colon tumor models, the combination therapy of NKTR-214 with anti-PD-1 therapy or anti-CTLA-4 therapy resulted in significant tumor growth inhibition. In the aggressive EMT6 breast tumor model, a single-agent anti-PD-1 therapy or single-agent anti-CTLA-4 therapy showed growth inhibition of 23%, but when dosing of NKTR-214 preceded anti-PD-1, the combination therapy showed stronger tumor growth inhibition at 74%.

The results were presented June 1 at the 2014 American Society of Clinical Oncology Annual Meeting in Chicago.

Nektar, which has 8 approved products between the U.S. and Europe, is continuing studies on NKTR-214 with an investigational new drug application in mind.

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