MK-3475治疗非小细胞肺癌显示出良好前景

Merck公司10月2日宣布，在一项Ib期研究中，接受免疫治疗药物MK-3475(lambrolizumab，anti-PD-1)治疗的难治性NSCLC患者的客观应答率为24%。MercK称，此项研究的结果是推进MK-3475进入II/III期研究的主要依据，具体结果将在10月29日召开的世界肺癌大会上公布。

Interim Data for Merck’s MK-3475, an Investigational Anti-PD-1 Immunotherapy, in Previously Treated Patients with Non-Small Cell Lung Cancer to be Presented at 15th World Conference on Lung Cancer

Public Company Information:
NYSE:MRK
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, confirmed today that interim data from the company’s Phase IB expansion study (PN 001) evaluating the efficacy and safety of *MK-3475 in patients with refractory non-small cell lung cancer (NSCLC) is scheduled for presentation at the 15th World Conference on Lung Cancer on Oct. 29 at 4:15 p.m., (1:15 a.m. EDT), in Sydney, Australia.

An abstract (# 2416) published today summarized preliminary findings from 38 patients with NSCLC treated with MK-3475. Data from additional patients and an analysis of tumor PD-L1 expression is scheduled to be presented by Dr. Edward Garon, Director of Thoracic Oncology, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, during the conference.

“These early data in lung cancer patients were the basis for Merck’s decision to rapidly advance MK-3475 into a Phase II/III clinical trial in NSCLC,” said Dr. Eric H. Rubin, vice president, Oncology, Merck Research Laboratories. “We look forward to further discussion of the data following its presentation at the conference.”

The published abstract describes early data for 38 patients with NSCLC treated with MK-3475 as a single agent dosed at 10mg/kg every three weeks. The preliminary objective response rate (confirmed and unconfirmed) was 24 percent as measured using investigator-assessed immune related response criteria (irRC) and 21 percent, (confirmed and unconfirmed), by RECIST v1.1. The most common treatment-related adverse events observed were fatigue, rash, and pruritus (16 percent each); diarrhea grade 1 or 2 occurred in 13 percent of patients. One case of a drug-related grade 3 pulmonary edema was reported.

38位患者，单药10mg/kg每三周
客观应答率：irRC->24% RECIST->21%
最常见的AE（发生率16%）：疲劳、皮疹、瘙痒
13%的患者发生1-2级腹泻
1位患者发生药物相关的3级肺水肿

About MK-3475

Many tumors are able to evade the immune system through a mechanism that exploits the PD-1 inhibitory checkpoint protein. MK-3475 is an investigational, highly selective anti-PD-1 immunotherapy designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, MK-3475 enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system.

MK-3475 is currently being studied in seven clinical trials estimated to enroll over 3,000 patients across a broad range of cancer types including: bladder, colorectal, head and neck, melanoma, non-small cell lung and triple negative breast. The expansion of MK-3475 clinical development program is based on preliminary clinical evidence from Merck’s large foundational Phase IB trial (PN 001) evaluating MK-3475 monotherapy in over 1,000 patients with diverse late stage cancers (metastatic carcinoma).

这个不是靶向药，是免疫治疗药物，似乎对于患者来说，更有利于长治久安治疗的目的。不知这样理解对不对。

也算靶向药吧，不过这个是抗体，很多癌细胞表达PD-1，可以阻止免疫细胞如T细胞对癌细胞的攻击，抗体阻断PD-1，免疫细胞可以识别杀死癌细胞。是很令人振奋的药，但是因为是抗体，生产很难，不会有非正版，所以上市以后会很贵，像西妥昔单抗。但还是好消息。同样的原理，别的公司也在做，效果也很好，希望竞争的结果，会有有效又相对便宜的药。

BMS936558单抗也是阻断PD-1过表达的，是不是阻断PD-1过表达的药物都必须是抗体药物呀，如果是，那草根抗癌群体就有可能消受不起了

望而却步啊。。。心存侥幸，万一有机会呢，呵呵。

ORR真心低 这也能进II/III期 各种不看好

啥时候能上市或有非正版啊？

根据最新临床试验数据显示，默沙东旗下抗PD-1药物Lambrolizumab(MK-3475)治疗的晚期黑色素瘤患者中，超过80%的患者在一年之后仍存活。来自默沙东Lambrolizumab的Ib期临床试验首批生存期数据巩固了之前的结果，之前结果显示该免疫疗法获得38%的总有效率，而在最高剂量（每两周10mg/kg）下总有效率可升至52%。
研究人员向本周费城举行的黑色素瘤研究学会国际会议上提交了该最新结果，透露又经过五个月的随访后总有效率增加到41%，有88%的患者呈现部分或完全缓解，其疾病未显示有进展。“我们的数据使我们满怀希望，该新试验药物有可能为患有这种恶性疾病的患者提供有意义的收益，”默沙东研发主管Roger Perlmutter如此评论道。
Lambrolizumab于今年四月份被FDA授予突破性治疗药物资格，该药物可激活患者自身的免疫系统，增强一种T细胞介导的免疫反应，通过去除肿瘤细胞用来帮助它们逃避检测的一种面具来对抗黑色素瘤。
目前进行的一项II期临床研究正将该药物与传统的化疗药物进行对比，受试者为经过先前治疗疾病仍有进展的患者，同时一项III临床试验将该药物与百时美施贵宝的CTLA-4抑制剂伊匹单抗(Ipilimumab)进行对比，伊匹单抗正在成为晚期黑色素瘤二线治疗的首选药物。
默沙东正为上市首款抗PD-1治疗药物而与其它制药商进行竞争，特别是百时美施贵宝，其Nivolumab候选药物正处于III期临床试验阶段，罗氏的MPDL3280A处于II期临床试验中，而阿斯利康有款抗PD-1药物MEDI4736和AMP-514，均处于早期试验中。分析人士估计Nivolumab将会第一个上市，其销售峰值大约为10亿美元，而Lambrolizumab预计投放市场会稍晚一些，其销售额每年会达到5亿美元。
除了黑色素瘤，抗PD-1受体类药物在治疗非小细胞肺癌(NSCLC)及肾癌方面已显示出成功的希望。Perlmutter于今年早些时候说，默沙东也对Lambrolizumab治疗激素受体阴性乳腺癌、神经上皮肿瘤、头颈癌及结直肠癌开始进行试验。默沙东称计划今年启动合并用药的临床试验，2014年初将在黑色素瘤和其他癌症基础上开展此项工作。

是啊，啥时有啊!