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美国FDA批准Keytruda扩展治疗晚期非小细胞肺癌

2015-10-04 09:29:19 作者：新特药房来源：互联网浏览次数：6 文字大小：【大】【中】【小】

简介： 2015年10月2日，美国食品和药品监管局(FDA)授权加快批准为Keytruda(pembrolizumab/MK-3475)治疗患者有晚期(转移)非-小细胞肺癌(NSCLC)其疾病在其它治疗和有表达蛋白被称为PD-L1的肿瘤。Keytruda是与批准使 ...

关键字：派姆单抗 pembrolizumab商品名 keytruda 突破性治疗非小细胞肺癌指定优先审评加快审批程序

2015年10月2日，美国食品和药品监管局(FDA)授权加快批准为Keytruda(pembrolizumab/MK-3475)治疗患者有晚期(转移)非-小细胞肺癌(NSCLC)其疾病在其它治疗和有表达蛋白被称为PD-L1的肿瘤。Keytruda是与批准使用一种协同诊断， PD-L1 IHC 22C3 pharmDx测试，第一个测试被设计检测在非-小细胞肺肿瘤表达PD-L1。
根据美国国家癌症研究所肺癌是美国癌症死亡的首要原因，在2015年有一个估算的221,200 新诊断和158,040例死亡。NSCLC是肺癌最常见类型。
FDA的药品评价和研究中心中血液学和肿瘤室主任Richard Pazdur，M.D.说：“我们对潜在的分子途径和我们的免疫系统如何与癌症的交互作用了解的日益增长导致医疗中重要的进展。” “今天Keytruda的批准给予医生靶向最可能从药物获益的特异性患者的能力。”
Keytruda通过靶向细胞通路被称为(机体的免疫细胞和某些癌症细胞上发现的蛋白)起作用。通过阻断这个通路，Keytruda可能有助于机体免疫系统与癌症细胞斗争。在2014年，Keytruda 被批准治疗用普利姆玛[ipilimumab]，免疫治疗的一种类型治疗后有晚期患。在2015年另一种药物，Opdivo (nivolumab)，由Bristol-Meyers Squibb公司制造，也靶向PD-1/PD-L1通路和被批准治疗鳞状上皮非-小细胞肺癌(NSCLC的某种类型)。
在550例有晚期NSCLC患者中研究Keytruda的安全性。Keytruda的最常见副作用包括疲乏，食欲减退，气短或受损的呼吸(呼吸困难)和咳嗽。Keytruda还有潜能致来自Keytruda的免疫系统结果(被称为 “免疫-介导副作用”)严重副作用。
在一项较大多中心，开放，多-部分研究内纳入一个61例患者亚组证实对这个使用Keytruda的有效性。这个亚组由有晚期NSCLC在基于铂化疗后进展或，如适当，对某些遗传突变(ALK或EGFR)靶向治疗患者组成。这个亚组还有PD-L1根据22C3 pharmDx诊断测试阳性肿瘤的结果。研究参加者接受10 mg/kg的Keytruda每2或2周。主要结局测量是总体反应率(患者经历他们的肿瘤完全和部分缩小患者的百分率)。用Keytruda治疗患者41%肿瘤缩小和效应持续2.1和9.1 个月间。
在550例有晚期NSCLC研究参加者，严重免疫-介导副作用发生涉及肺，结肠和激素-产生腺。其他不常见免疫-介导副作用为皮疹和血管炎症(血管炎)。妊娠或哺乳喂养妇女不应用 Keytruda因为它可能危害发育中胎儿或新生儿。跨越临床研究，还发生一种疾病其中机体的免疫系统攻击的周围神经系统的一部分(Guillain-Barre综合证)。
FDA授权Keytruda对这个适应证突破性治疗指定因为Merck证实通过初步临床证据药物可能提供超过可得到治疗的一种实质上改进。药物还接受优先审评状态，它被授权于药物在这个时间申请被递交，有将是在一种严重情况治疗中在安全性或有效性显著改进的潜能。
Keytruda是在监管局加快批准程序下被批准，这个程序允许根据临床数据显示该药物对一个替代性终点可能合理地预测对患者临床获益批准一个药物治疗一个严重或危及生命疾病。这个程序提供This program provides earlier 患者较早得到鼓舞人有前途新药而公司进行验证性临床试验。未曽确定用Keytruda 治疗在正在被治疗患者中生存或疾病相关症状改善。
Keytruda由总部设在新泽西白宫站默克公司上市和PD-L1 IHC 22C3 pharmDx诊断测试由加州 Carpinteria的Dako North America公司上市。
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125514s005lbl.pdf
HOW SUPPLIED/STORAGE AND HANDLING
KEYTRUDA for injection (lyophilized powder): carton containing one 50 mg single-use vial (NDC 0006-3029-02).
Store vials under refrigeration at 2°C to 8°C (36°F to 46°F).
KEYTRUDA injection (solution): carton containing one 100 mg/4 mL (25 mg/mL), single-use vial (NDC 0006-3026-02)
Store vials under refrigeration at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Do not shake.
New Drugs Online Report for pembrolizumab
Information
Generic Name: pembrolizumab
Trade Name: Keytruda
Synonym: MK 3475, SCH900475
Entry Type: New molecular entity
Development and Regulatory status
UK: Phase III Clinical Trials
EU: Phase III Clinical Trials
US: Pre-registration (Filed)
UK launch Plans: Available only to registered users
Actual UK launch date:
Comments
June 15: The FDA has accepted for review the sBLA for KEYTRUDA® (pembrolizumab), to treat pts with advanced NSCLC whose disease has progressed on or after platinum-containing chemotherapy. The FDA granted Priority Review with a target action date of October 2, 2015 and the sBLA will be reviewed under the FDA’s Accelerated Approval program [6].
03/06/2015 14:55:10
Apr 15: Filed in the US for use in patients with advanced NSCLC whose disease has progressed despite platinum-containing chemotherapy and a therapy for certain mutations (if present) [5].
20/04/2015 13:35:00
Oct 14: Granted breakthrough therapy status in the US for NSCLC which has progressed on or following platinum-based chemotherapy [4].
27/10/2014 16:42:51
Trial or other data
Aug 14: Pfizer and Merck announce they will explore the therapeutic potential of marrying Pfizer’s Xalkori (crizotinib) with Merck’s anti-PD-1 antibody pembrolizumab in a PIb clinical study assessing safety and tolerability in patients with ALK-positive advanced or metastatic NSCLC. Pfizer will conduct the multi-center, open-label study, which is expected to begin sometime next year, but further specifics of the deal were not disclosed [3].
27/08/2014 12:13:20
Jun 14: Data presented at ASCO show a group of previously untreated patients with NSCLC, pembrolizumab triggered a 47% response rate. And for another group of evaluable patients with one post baseline scan, the response rate was 80%. The median figure for the duration of response still hasn´t been determined in the study, with some patients being treated for up to a year now. The lung cancer data in Phase Ib sets the stage for a pivotal PIII study that Merck plans to start in in Q4 2014 [2].
09/06/2014 12:23:15
Jul 13: NCT01905657 (MK-3475-010) this PIII study will compare two doses of lambrolizumab vs docetaxel in 920 participants with NSCLC who have experienced disease progression after platinum-containing systemic therapy. Participants will be assigned randomly to either low or high dose lambrolizumab every three weeks (or docetaxel at 75 mg/m^2 every 3 weeks). The study will use an adaptive trial design so that the total number of participants randomized will depend on demonstration of sufficient objective responses at interim analysis. If the lambrolizumab low dose arm is closed, participants may receive lambrolizumab high dose therapy. The co-primary endpoints are PFS and OS. The study starts Aug 13 and is due to complete in 2020 (primary outcome data collection Sep 15). [1].
29/07/2013 11:50:32
Evidence Based Evaluations
NHSC/NIHR http://www.hsc.nihr.ac.uk/topics/mk-3475-for-advanced-or-recurrent-pd-l1-positive-n/
References
Available only to registered users
Category
BNF Category: Other immunomodulating drugs (08.02.04)
Pharmacology: Humanised monoclonal IgG4 antibody against the programmed death-1 (PD-1) protein
Epidemiology: The incidence rate of lung cancer in 2006 was 72.2 per 100,000 in men and 50.8 per 100,000 in women. Lung cancer belongs to the three most common cancers in men (14.8 % of all cancers) and women (10.9% of all cancers).
Indication: Non-small cell lung cancer (NSCLC)
Additional Details: PD-1 positive - second-line
Method(s) of Administration
Intravenous
Company Information
Name: Merck Sharp & Dohme
US Name: Merck Pharmaceuticals
Further Information
Anticipated commissioning route (England) NHSE
High cost drug list? Awaiting Update
Implications Available only to registered users