医脉通编译整理，转载请务必注明出处。
2016年6月3-7日，一年一度的美国临床肿瘤学会（American SocietyofClinicalOncology, ASCO）年会将在芝加哥举办。本次大会将吸引30000名全世界的肿瘤领域专家学者和参会人员，会议摘要收录了多个我国学者主导的肿瘤前沿研究。
由广东省人民医院副院长、国内肺癌领域的顶尖专家吴一龙教授带领的国际多中心团队开展了一项单臂、开放标签的Ⅰb/Ⅱ临床研究，主要目的是评估cMET靶向药物INC280联合吉非替尼治疗EGFR TKI治疗进展的cMET+非小细胞肺癌（NSCLC）患者的安全性和疗效。在2014年ASCO年会上，该研究Ⅰb期结果显示口服INC280联合吉非替尼耐受性良好，且未发现INC280与吉非替尼在药代动力学上有相互作用。
对于伴随EGFR基因突变的NSCLC患者，大多数在经过EGFR酪氨酸激酶抑制剂（TKI）治疗后会出现耐药，而癌细胞cMET扩增是获得性耐药的原因之一，约占15%-25%。INC280是一种高选择性口服小分子cMET抑制剂，在cMET+ NSCLC患者中与EGFR TKI联合使用显现出一定的临床效用。2016年ASCO年会上，吴一龙教授团队将公布Ⅱ期扩大研究的结果。
摘要编号：9020
时间：6月4日，上午8:00-11:30
报告形式：壁报展示
患者主要入组标准：
◆年龄≥18岁
◆NSCLC
◆EGFR+（exon19del/L858R，无T790M）
◆曾接受过EGFR TKI治疗并有可测量的临床获益
◆耐药后cMET+（免疫组化3+, 或免疫组化2+且基因拷贝数[GCN] ≥ 5）
◆ECOG PS≤2
◆期望寿命≥3个月
截至2015年9月，该研究Ⅱ期扩大试验共纳入83名患者。Ⅱ期推荐剂量（RP2D）为INC280/400mg（BID）+吉非替尼/250mg（QD）。
Ⅱ期研究主要目标是评价INC280联合吉非替尼的总体临床效用，次要目标是评价治疗方案安全性、耐受性和时间依赖的临床效用。
结果
在83例入组肺癌患者中，66例（80%）曾接受EGFR TKI单药或联合治疗，42例（51%）中断了治疗，多数（34%）是因为疾病进展。
在65例可评估肺癌患者中，治疗后12例出现部分缓解（ORR=18%），40例肿瘤稳定（SD=62%），疾病总体控制（ORR+SD）率为80%。
在53例IHC 3+或IHC 2+且GCN≥ 5的肺癌患者中，10例出现部分缓解（ORR=19%）；
在23例GCN≥ 6的肺癌患者中，7例出现部分缓解（ORR=30%）。
最常见的不良反应依次为低蛋白血症（29%）、周围性水肿（27%）、食欲减退（23%）。最常见的3-4级不良反应为淀粉酶升高（7%）。
结论
对于EGFR TKI 耐药的cMET+NSCLC患者，ICN280/400mg（BID）联合吉非替尼治疗具有较好的耐受性，并表现出一定的临床疗效。cMET基因拷贝数高的患者可能临床获益更大。
会议专题》》》2016年ASCO年会专题报道
摘要阅读
Abstract No: 9020
Phase (Ph) II safety and efficacy results of a single-arm ph ib/II study of capmatinib (INC280) + gefitinib in patients (pts) with EGFR-mutated (mut), cMET-positive (cMET+) non-small cell lung cancer (NSCLC)
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Author(s): Yi-Long Wu,Dong-Wan Kim,Enriqueta Felip,et al.
Background: Most pts with EGFR-mut NSCLC progress on EGFR tyrosine kinase inhibitor (TKI) therapy despite high initial response rates. cMET is dysregulated in 15?25% of NSCLC pts with acquired EGFR TKI resistance. INC280 is a highly selective cMET inhibitor with preclinical and preliminary clinical activity in EGFR-mut, cMET+ NSCLC when combined with EGFR TKIs. This Ph Ib/II study evaluates the safety and efficacy of INC280 + gefitinib in pts with EGFR-mut, cMET+ NSCLC who have progressed on gefitinib, erlotinib, or afatinib (NCT01610336). We report here on the Ph II expansion part.
Methods: The Ph II primary objective is to estimate the overall clinical activity of INC280 + gefitinib. Secondary objectives include assessing safety and tolerability, and time-dependent clinical activity. Eligible pts ( ≥18 years; ECOG PS ≤ 2) must have documented EGFR-mut (exon19del/L858R; no T790M) NSCLC. Pts must have had RECIST-recorded clinical benefit on prior single-agent EGFR TKI before progression, and centrally assessed cMET+ (IHC 3+, or IHC 2+ and gene copy number [GCN] ≥ 5) post-progression. Pts were treated at the RP2D of INC280 400 mg BID (tablet/capsule) + gefitinib 250 mg QD.
Results: As of Sep 28 2015, 83 pts were enrolled in the Ph II expansion part (median age 61 years; 84% Asian; 14% PS 0; 55% had 1 prior line of therapy). 66/83 (80%) pts received EGFR TKI as their last single or combined therapy. 42/83 (51%) pts discontinued treatment, mainly due to disease progression (34%). The most common AEs (regardless of causality) were hypoalbuminemia (29%), peripheral edema (27%), and decreased appetite (23%). The most common Grade 3/4 AE (regardless of causality) was increased amylase (7%). Partial responses (PRs) were seen in 12/65 evaluable pts (ORR 18%) and 40/65 (62%) pts had stable disease (SD); disease control rate [PR + SD] 80%. 10/53 pts with IHC 3+ or IHC 2+ and GCN ≥ 5 had PRs (ORR 19%) and 7/23 pts with GCN ≥ 6 had PRs (ORR 30%).
Conclusions: INC280 400 mg BID + gefitinib is well-tolerated and shows encouraging clinical activity in EGFR TKI-resistant NSCLC pts, particularly in pts with high cMET GCN. Clinical trial information: NCT01610336
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医脉通编译自：Yi-Long Wu,et al. Phase(Ph) II safety and efficacy results of a single-arm ph ib/II study ofcapmatinib (INC280) + gefitinib in patients (pts) with EGFR-mutated (mut),cMET-positive (cMET+) non-small cell lung cancer (NSCLC).JClin Oncol 34, 2016 (suppl; abstr 9020).
