nsclc精准靶向治疗进展alkmet靶点

1、1会计学nsclc精准靶向治疗进展精准靶向治疗进展alkmet靶点靶点Effect of expanded genomic testing in lung adenocarcinoma (LUCA) on survival benefit: The Lung Cancer Mutation Consortium II (LCMC II) experienceASCO 2016, Abstract 11510uALK靶点的治疗进展uMET靶点的治疗进展ALK TKIROS1 activityStatusOngoing StudiesCeritinibYesFDA Approved(4-29-20

2、14)Phase 3(vs. chemo)AlectinibNoApproved in Japan(7-4-2014) FDA Breakthrough TherapyDesignationPhase 3(vs. crizotinib)AP26113YesInvestigationalPhase 2X-396YesInvestigationalPhase 1TSR-011NoInvestigationalPhase 1/2aRXDX-101YesInvestigationalPhase 1/2aCEP-37440UnkInvestigationalPhase 1PF-06463922YesIn

3、vestigationalPhase 1/2Pall G. Current Opinion in Oncology 2015激酶抑制活性激酶抑制活性在小在小鼠鼠模型对颅内模型对颅内ALK阳性肿瘤的活性阳性肿瘤的活性B/期或复发的期或复发的ALK阳阳性性NSCLCALK中心实验室检测中心实验室检测(IHC和和FISH或或RT-PCR)ECOG评分评分02研究者评估的研究者评估的 1可测量病可测量病灶灶经治经治/无症状脑转移可入无症状脑转移可入组组既往既往未接受化疗或未接受化疗或1次化疗次化疗Alectinib，300 mg，BID PO,28天一周期天一周期（n=100）克唑替尼克唑替尼，250

4、 mg，BID PO,28天一周期天一周期（n=100）主要终点：主要终点：-PFS(独立评审独立评审委员会评估委员会评估)次要终点次要终点-OS-ORR-PK-QOL-CNS PFS-安全性安全性R 1:1特征特征Alectinib（n=103）克唑替尼（克唑替尼（n=104）性别男/女41（39.8%）/62（60.2%）41（39.4%）/63（60.6%）中位年龄（范围）61.0（27-85）59.5（25-84）ECOG PS*0/1/254（52.4%）/47（45.6%）/2（1.9%）48（46.2%）/54（51.9%）/2（1.9%）既往化疗疗程*0/166（64.1%）/

5、37（35.9%）67（64.4%）/37（35.6%）临床分期*IIIb/IV/术后复发3（2.9%）/76（73.8%）/24（23.3%）3（2.9%）/75（72.1%）/26（25.0%）组织学鳞癌/腺癌/其他2（1.9%）/100（97.1%）/1（1.0%)0/103（99.0%）/1（1.0%）脑转移（独立评审）是/否14（13.6%）/89（86.4%）29（27.9%）/75（72.1%）吸烟状态从不/既往或目前56（54.4%）/47（45.6%）61（58.7%）/43（41.3%）ALK检测方法IHC及FISH/RT-PCR96（93.2%）/7（6.8%）94（90

6、.4%）/10（9.6%）*分层因素Alectinib（n=103）克唑替尼克唑替尼（n=104）任何AE100（97.1%）104（100.0%）3/4级级AE27（26.2%）54（51.9%）治疗相关死亡00SAE15（14.6%）27（26.0%）由于由于AE中断中断治疗治疗9（8.7%）21（20.2%）由于由于AE药物药物减量减量30（29.1%）77（74.0%）导致治疗导致治疗中断中断AEAlectinib（9）克唑替尼克唑替尼（23）ILD88小肠结肠炎10肝功能异常05 ALT升高04 AST升高01血胆红素升高01QT延长01心动过缓01急性髓性白血病01斑丘样皮疹01所

7、有级别所有级别3/4级级Alectinib（n=103）克唑替尼克唑替尼（n=104）Alectinib（n=103）克唑替尼克唑替尼（n=104）便秘便秘36（35.0%）46（44.2%）1（1.0%）1（1.0%）恶心恶心11（10.7%）77（74.0%）02（1.9%）腹泻腹泻9（8.7%）76（73.1%）02（1.9%）呕吐呕吐6（5.8%）60（57.7%）02（1.9%）AST升高升高11（10.7%）32（30.8%）1（1.0%）5（4.8%）ALT升高升高9（8.7%）33（31.7%）1（1.0%）13（12.5%）视力障碍视力障碍1（1.0%）57（54.8%）00

8、鼻咽炎21（20.4%）24（23.1%）00味觉障碍味觉障碍19（18.4%）54（51.9%）00发热10（9.7%）21（20.2%）1（1.0%）0食欲下降1（1.0%）21（20.2%）1（1.0%）1（1.0%）研究者评估研究者评估ITT人群人群Alectinib（n=103）克唑替尼克唑替尼（n=104）ORR95% CI85.4%78.6-92.3 70.2%61.4-79.0CR 或 PR8873IRF评估评估Alectinib（n=83）克唑替尼克唑替尼（n=90）ORR95% CI91.6%85.6-97.5 78.9%70.5-87.3CR 或 PR7671uALK靶点

9、的治疗进展uMET靶点的治疗进展方法：用免疫组化技术（IHC）检测晚期NSCLC患者de novo c-Met表达情况，FISH技术检测基因拷贝数变化。c-Met阳性为有50%以上肿瘤细胞中高强度染色Abstract titleAbstract IDEfficacy and safety of crizotinib in patients (pts) with advanced MET exon 14-altered non-small cell lung cancer (NSCLC) 108Crizotinib in children and adolescents with advance

10、d ROS1, MET, or ALK-rearranged cancer: Results of the AcS phase II trial 11509Amethyst NSCLC trial: Phase 2, parallel-arm study of receptor tyrosine kinase (RTK) inhibitor, MGCD265, in patients (pts) with advanced or metastatic non-small cell lung cancer (NSCLC) with activating genetic alterations i

11、n mesenchymal-epithelial transition factor (MET)TPS9099Comprehensive genomic profiling of 298 lung cancers of varying histologies harboring MET exon 14 alterations (poster discussion)9021Phase (Ph) II safety and efficacy results of a single-arm ph ib/II study of capmatinib (INC280) + gefitinib in pa

12、tients (pts) with EGFRmutated (mut), cMET-positive (cMET+) non-small cell lung cancer(NSCLC) 9020Phase (Ph) I study of the safety and efficacy of the cMET inhibitor capmatinib (INC280) in patients (pts) with advanced cMET+ nonsmall cell lung cancer (NSCLC)9067GEOMETRY duo-1: A phase (Ph) Ib/II, mult

13、icenter trial of oral cMET inhibitor capmatinib (INC280) erlotinib vs platinum + pemetrexed in adult patients (pts) with epidermal growth factor receptor (EGFR)-mutated, cMET-amplified, locally advanced/metastatic non-small cell lung cancer (NSCLC) with acquired resistance to prior EGFR tyrosine kin

14、ase inhibitor (TKI) therapy.TPS9109A randomized, open-label, phase 2 study of emibetuzumab plus erlotinib (LY+E) and emibetuzumab monotherapy (LY) in patients with acquired resistance to erlotinib and MET diagnostic positive (MET Dx+) metastatic NSCLC9070Phase 1, open-label, dose-escalation and expa

15、nsion study of ABBV-399, an antibody drug conjugate (ADC) targeting c-Met, in patients (pts) with advanced solid tumors2510Response to tyrosine kinase inhibitors in advanced non-small-cell lung cancer with concomitant c-MET overexpression and EGFR mutation9054MET 14外显子剪接突变外显子剪接突变ASCO 2016, Abstract

16、108l 随着检测技术的突飞猛进，越来越多的驱动基因被发现，NSCLC的分子分型也越来越精准。l 针对驱动基因的靶向治疗，包括在ALK及MET突变NSCLC的治疗中取得了飞跃。谢谢您的参与、呤听！Alectinib（n=103）克唑替尼克唑替尼（n=104）任何AE100（97.1%）104（100.0%）3/4级级AE27（26.2%）54（51.9%）治疗相关死亡00SAE15（14.6%）27（26.0%）由于由于AE中断中断治疗治疗9（8.7%）21（20.2%）由于由于AE药物药物减量减量30（29.1%）77（74.0%）导致治疗导致治疗中断中断AEAlectinib（9）克唑替尼克唑替尼（23）