文章来源：医脉通

2015年ASCO年会将于5月29日--6月2日在美国芝加哥召开。5月31日下午的肺癌免疫治疗专场，将公布Ⅰ期研究KEYNOTE-021队列D的研究结果。该研究结果表明，pembrolizumab加ipilimumab作为晚期非小细胞肺癌的二线治疗安全有效（摘要号8011）。医脉通对此进行了报道。

Pembrolizumab（pembro)是一种有效的抗PD-1单克隆抗体。Ipilimumab（IPI）是一种抗CTLA-4抗体，已经在晚期NSCLC中显示出有效性。对于黑色素瘤，抗PD-1和抗CTLA-4联合治疗已经显示出强大的功效和可控的毒性。我们将报告一项评估pembro + IPI治疗复发性NSCLC研究的中期结果。

相关报道：[2015 ASCO GI]KEYNOTE-012研究:Pembrolizumab用于胃癌安全有效

研究纳入了既往经≤2种治疗方案后复发的IIIB/IV期NSCLC患者。使他们接受 pembro + IPI 治疗，每三周一次，共4个周期，随后采用pembro维持治疗。基于nivolumab + IPI 治疗晚期NSCLC研究的新数据，pembro的剂量从10mg/kg 降到2mg/kg， IPI的剂量从3mg/kg降到1mg/kg。主要终点是安全和前3周给药剂量的剂量限制毒性（DLTs)发生率。调查者根据RECIST1.1评估缓解，每6周评估一次。

到2014年12月，入组17例患者：3位患者接受pembro 10mg/kg+IPI 3mg/kg、3位接受pembro 10mg/kg + IPI 1mg/kg，11位接受pembro 2mg/kg + IPI 1mg/kg。分析时，治疗的15例患者没有发生DLTs或剂量调整。10例患者发生药物相关的AEs（DRAEs）但没有人停止治疗或死亡。有2次3度 DRAEs，都是皮疹。2度DRAE是腹泻和呕吐（各2例）、寒战，咳嗽，食欲减退，体重下降，脱水，抑郁症，发音困难，乏力，肌痛，皮肤瘙痒和发热（各1例）。分析时，治疗 ≥ 6周时各剂量组的11位患者都可观察到缓解，其中包括1例CR(9%)和5例PRs(45%)（见表)；所有的患者都获得了疾病控制。12例pts仍然在治疗（范围6＋到26+周）；3位患者由于PD停药。

KEYNOTE-021 队列D的初始数据表明，pembro+ IPI对于复发性NSCLC患者，具有可接受的毒性作用和强大的抗肿瘤活性。使用较低剂量的pembro和IPI不会降低效果。临床试验信息：NCT02039674

会议专题》》》2015年ASCO年会专题报道

摘要原文（摘要号8011）

Background: Pembro is a potent anti–PD-1 monoclonal antibody. IPI, an anti–CTLA-4 antibody, has shown activity in advanced NSCLC. In melanoma, combined anti–PD-1 and anti–CTLA-4 treatment has shown robust efficacy and manageable toxicity. We report interim results from a phase 1 study evaluating pembro + IPI in patients (pts) with recurrent NSCLC.

Methods: Pts with stage IIIB/IV NSCLC that recurred after ≤ 2 prior regimens received pembro + IPI every 3 wk for 4 cycles followed by maintenance pembro. Based on emerging data from the nivolumab + IPI advanced NSCLC study, doses were reduced from 10 mg/kg to 2 mg/kg for pembro and from 3 mg/kg to 1 mg/kg for IPI). Primary end point was safety and incidence of dose-limiting toxicities (DLTs) in the first 3 wk of dosing. Response was assessed every 6 wk per RECIST 1.1 by investigator review.

Results: As of Dec 2014,17 pts were enrolled: 3 at pembro 10 mg/kg + IPI 3 mg/kg, 3 at pembro 10 mg/kg + IPI 1 mg/kg, and 11 at pembro 2 mg/kg + IPI 1 mg/kg. No DLTs or dose modifications were reported for the 15 pts treated at the time of analysis. 10 pts experienced drug-related AEs (DRAEs); none led to discontinuation or death. There were 2 gr 3 DRAEs, both rash. Gr 2 DRAEs were diarrhea and vomiting (n = 2 each) and chills, cough, decreased appetite, decreased weight, dehydration, depression, dysphonia, fatigue, myalgia, pruritus, and pyrexia (n = 1 each). Responses were seen in all dose groups among the 11 pts on treatment for ≥ 6 wk at the time of analysis, including 1 CR (9%) and 5 PRs (45%) (Table); all pts achieved disease control. 12 pts remain on treatment (range, 6 + to 26 + wk); 3 pts discontinued for PD.

Conclusions: Preliminary data from KEYNOTE-021 cohort D demonstrate an acceptable toxicity profile and robust antitumor activity for pembro + IPI in pts with recurrent NSCLC.The use of lower pembro and IPI doses did not appear to negatively impact efficacy. Clinical trial information: NCT02039674