ASCO肺癌靶向治療新進(jìn)展培訓(xùn)課件

1、1ASCO肺癌靶向治療新進(jìn)展10/2/20221ASCO肺癌靶向治療新進(jìn)展10/1/20222ASCO肺癌靶向治療新進(jìn)展10/2/20222ASCO肺癌靶向治療新進(jìn)展10/1/2022主要內(nèi)容EGFR： 克服耐藥：JNJ-372，U3-1402 延緩耐藥： RELAY研究，化療+TKI，9291+A EGFR-20插入： JNJ-372， TAK788K-RAS：AMG510，曲美替尼+多西他賽ALK：J-ALEX更新，Brigatinib 后線ROS1：RepotrectinibC-met：Tepotinib，CapmatinibRET：BLU-667Her-2：吡咯替尼B-raf: NTR

2、Ks：NCCN指南推薦檢測(cè)八個(gè)基因+K-RAS3ASCO肺癌靶向治療新進(jìn)展10/2/2022主要內(nèi)容EGFR：NCCN指南推薦檢測(cè)八個(gè)基因+K-RAS3主要內(nèi)容EGFR： 克服耐藥：JNJ-372，U3-1402， 延緩耐藥： RELAY研究，化療+TKI，9291+A EGFR-20插入： JNJ-372， TAK788K-RAS：AMG510，曲美替尼+多西他賽ALK：J-ALEX更新，Brigatinib 后線ROS1：RepotrectinibC-met：Tepotinib，CapmatinibRET：BLU-667Her-2：吡咯替尼B-raf: NTRKs：NCCN指南推薦檢測(cè)八個(gè)

3、基因+K-RAS4ASCO肺癌靶向治療新進(jìn)展10/2/2022主要內(nèi)容EGFR：NCCN指南推薦檢測(cè)八個(gè)基因+K-RAS4厄洛替尼吉非替尼含鉑類化療PFS（月）?？颂婺?0項(xiàng)TKI vs. CT的RCT奠定了EGFR-TKI為EGFR+的NSCLC一線標(biāo)準(zhǔn)治療的地位Chen G, et al. Ann Oncol 2013;24:161522; Gefitinib Summary of Product Characteristics 2010; Han JY, et al. J Clin Oncol.2012;30:11228; Maemondo M, et al. N Engl J Med.

4、2010;362:23808; Mok T, et al. N Engl J Med.2009; 361:94757; Mitsudomi T, et al. Lancet Oncol.2010;11:1218; Rosell R, et al.Lancet Oncol.2012;13:23946; Sequist LV, et al. J Clin Oncol.2013;31:332734; Soria JC, et al. N Engl J Med. 2018 Jan 11;378(2):113-125. Wu YL, et al. Lancet Oncol.2014;15:21322;

5、Wu YL, et al. Ann Onc.2015; Ann Oncol.2015; 26:1883-9; Zhou C, et al. Lancet Oncol.2011; 8:73542.阿法替尼5ASCO肺癌靶向治療新進(jìn)展10/2/2022厄洛替尼吉非替尼含鉑類化療PFS（月）?？颂婺?0項(xiàng)TKI 二代 vs. 一代TKI無進(jìn)展生存率（%）100806040200時(shí)間（月）03691215182124273033263942454851阿法替尼（n=160）吉非替尼（n=159）中位數(shù)，月11.010.9HR（95% CI）p值0.74（0.57-0.95）0.017827%16%16

6、%8%達(dá)可替尼（N=227）吉非替尼（N=225）中位數(shù)，月14.79.2HR（95% CI）p值0.59 (0.47 - 0.74)p0.0001042363024181260.00.20.40.60.81.0PFS概率月刪失PFS率30.6% vs 9.6%LUX-Lung 7ARCHER-10506ASCO肺癌靶向治療新進(jìn)展10/2/2022二代 vs. 一代TKI無進(jìn)展生存率（%）100806040二代 vs. 一代TKIJ Clin Oncol.2018 Jun 4第一個(gè)OS陽性結(jié)果阿法替尼 vs 吉非替尼 達(dá)克替尼 vs 吉非替尼Paz-Ares et al. Ann Oncol

7、20177ASCO肺癌靶向治療新進(jìn)展10/2/2022二代 vs. 一代TKIJ Clin Oncol.2018PFSWHO體力狀態(tài)為0 / 1*日本為年齡20 ； #中心實(shí)驗(yàn)室進(jìn)行敏感性評(píng)估； cobas EGFR 突變檢測(cè)(Roche Molecular Systems);Sites在研究中心啟動(dòng)前選擇吉非替尼或厄洛替尼作為唯一對(duì)照藥的研究中心；18個(gè)月后每12周一次；CNS，中樞神經(jīng)系統(tǒng)；EGFR，表皮生長因子受體；NSCLC，非小細(xì)胞肺癌；PFS，無進(jìn)展期； p.o，口服；RECIST 1.1，1.1版實(shí)體瘤療效評(píng)價(jià)標(biāo)準(zhǔn)；qd，每日一次；SoC，標(biāo)準(zhǔn)治療；FLAURA數(shù)據(jù)截止日期：20

8、17年6月12日；NCT02296125Ramalingam SS, et al. 2017 ESMO Abstract LBA2.本研究有90%的把握度以雙側(cè)5%的水平檢出0.71的風(fēng)險(xiǎn)比(代表中位PFS從10個(gè)月延長至14.1個(gè)月)次要終點(diǎn)：客觀緩解率、緩解持續(xù)時(shí)間、疾病控制率、緩解深度、總生存期、患者自評(píng)結(jié)果、安全性 按突變狀態(tài)(Del 19/ L858R) 和種族(亞裔/非亞裔)分層奧希替尼(80 mg p.o. qd)(n=279)EGFR-TKI SoC;吉非替尼 (250 mg p.o. qd) 或厄洛替尼 (150mg p.o. qd) (n=277)每6周進(jìn)行一次RECIST

9、 1.1評(píng)估，直至出現(xiàn)客觀疾病進(jìn)展SoC組患者允許交叉，如果中心實(shí)驗(yàn)室確認(rèn)疾病進(jìn)展且T790M陽性，患者可接受奧希替尼開放治療FLAURA雙盲研究設(shè)計(jì)局部晚期或轉(zhuǎn)移性NSCLC的患者關(guān)鍵入選標(biāo)準(zhǔn) 18歲*R Del 19/ L858R(當(dāng)?shù)? 或中心實(shí)驗(yàn)室EGFR檢測(cè)) 既往未接受全身性抗癌/ EGFR-TKI 治療 允許穩(wěn)定性CNS 轉(zhuǎn)移1:1主要終點(diǎn)：研究者評(píng)估的PFS (基于RECIST 1.1)ORR (95%Cl)奧希替尼(n=279)80% (75,85)SoC(n=277)76% (70,81)OR# (95%Cl)1.28 (0.85,1.93); P=0.2335CR, n(

10、%)PR, n(%)SD6周, n(%)進(jìn)展, n(%)不可評(píng)估, n(%)7 (3)216 (77)47 (17)3 (1)6 (2)4 (1)206 (74)46 (17)14 (5)7 (3)仍持續(xù)緩解估值,(95%Cl)12個(gè)月18個(gè)月中位DOR (月)64% (58, 71)49% (41, 56)17.2(N=223)37% (31, 44)19% (13, 26)8.5(N=210)0151821242712時(shí)間 (月)0.20.00.80.60.41.0奧希替尼(n=279)標(biāo)準(zhǔn)治療(SoC)(n=277)中位PFS, 月 (95% Cl)18.9 (15.2， 21.4)10

11、.2 (9.6, 11.1)HR 0.46(95% Cl 0.37, 0.57)P0.00013 6 9三代 vs. 一代TKIOS仍不成熟8ASCO肺癌靶向治療新進(jìn)展10/2/2022PFSWHO體力狀態(tài)為0 / 1*日本為年齡20 ； #三代同堂9ASCO肺癌靶向治療新進(jìn)展10/2/2022三代同堂9ASCO肺癌靶向治療新進(jìn)展10/1/2022EGFR-TKIs耐藥：Camidge, et al. Nat Rev Clin Oncol.2014Aug;11(8):473-81.FLAURA研究: 奧希替尼 (n=91)*的獲得性耐藥機(jī)制10ASCO肺癌靶向治療新進(jìn)展10/2/2022EGF

12、R-TKIs耐藥：Camidge, et al. Na解決治療瓶頸的策略1、克服耐藥2、延緩耐藥11ASCO肺癌靶向治療新進(jìn)展10/2/2022解決治療瓶頸的策略1、克服耐藥11ASCO肺癌靶向治療新進(jìn)展克服T790M介導(dǎo)的耐藥：9291第三代TKI直接一線使用克服耐藥（T790M）1、N Engl J Med. 2017 Feb 16;376(7):629-640； 2、N Engl J Med. 2018 Jan 11;378(2):113-12512ASCO肺癌靶向治療新進(jìn)展10/2/2022克服T790M介導(dǎo)的耐藥：9291第三代TKI直接一線使用克Clinical trials -

13、EGFR + cMET inhibitors the world of TKIsPresented By Jessica Bauman at 2019 ASCO Annual Meeting克服c-met介導(dǎo)耐藥的臨床研究13ASCO肺癌靶向治療新進(jìn)展10/2/2022Clinical trials - EGFR + cMET 新藥： EGFR-cMET雙特異性抗體JNJ-37214ASCO肺癌靶向治療新進(jìn)展10/2/2022新藥： EGFR-cMET雙特異性抗體JNJ-37214AS新藥： EGFR-cMET雙特異性抗體JNJ-37215ASCO肺癌靶向治療新進(jìn)展10/2/2022新藥： E

14、GFR-cMET雙特異性抗體JNJ-37215AS作用機(jī)制16ASCO肺癌靶向治療新進(jìn)展10/2/2022作用機(jī)制16ASCO肺癌靶向治療新進(jìn)展10/1/2022研究設(shè)計(jì)17ASCO肺癌靶向治療新進(jìn)展10/2/2022研究設(shè)計(jì)17ASCO肺癌靶向治療新進(jìn)展10/1/2022入組患者特征18ASCO肺癌靶向治療新進(jìn)展10/2/2022入組患者特征18ASCO肺癌靶向治療新進(jìn)展10/1/2022Slide 12JNJ-372用于C797S、20ins、MET擴(kuò)增患者有效 32/108 (30%)19ASCO肺癌靶向治療新進(jìn)展10/2/2022Slide 12JNJ-372用于C797S、20ins

15、、MPost 3GTKI:RR 28%exon20ins:RR 30%克服第三代TKI耐藥： JNJ-372C797S、c-met擴(kuò)增、其他機(jī)制均有一定有效率ORR=28%，N=5820ASCO肺癌靶向治療新進(jìn)展10/2/2022Post 3GTKI:RR 28%Safety and preliminary antitumor activity of U3-1402, a HER3-targeted antibody drug conjugate, in EGFR TKI-resistant, EGFRm NSCLC Presented By Pasi Janne at 2019 ASCO A

16、nnual Meeting克服耐藥：新藥U3-140221ASCO肺癌靶向治療新進(jìn)展10/2/2022Safety and preliminary Slide 4Presented By Pasi Janne at 2019 ASCO Annual MeetingHer-3廣泛表達(dá)于EGFR突變細(xì)胞22ASCO肺癌靶向治療新進(jìn)展10/2/2022Slide 4Presented By Pasi JanneSlide 5Presented By Pasi Janne at 2019 ASCO Annual Meeting藥物設(shè)計(jì)23ASCO肺癌靶向治療新進(jìn)展10/2/2022Slide 5Pre

17、sented By Pasi JanneSlide 11Presented By Pasi Janne at 2019 ASCO Annual Meeting研究設(shè)計(jì)24ASCO肺癌靶向治療新進(jìn)展10/2/2022Slide 11Presented By Pasi JannSlide 15Presented By Pasi Janne at 2019 ASCO Annual MeetingORR=31%療效數(shù)據(jù)25ASCO肺癌靶向治療新進(jìn)展10/2/2022Slide 15Presented By Pasi Jann解決治療瓶頸的策略1、克服耐藥2、延緩耐藥26ASCO肺癌靶向治療新進(jìn)展10/

18、2/2022解決治療瓶頸的策略1、克服耐藥26ASCO肺癌靶向治療新進(jìn)展延緩耐藥：A+T JO25567：厄洛替尼 貝伐珠單抗（II期） NEJ026：厄洛替尼 貝伐珠單抗（III期） 2018-ASCO27ASCO肺癌靶向治療新進(jìn)展10/2/2022延緩耐藥：A+T JO25567：厄洛替尼 貝伐珠單抗（RELAY: A multicenter, double-blind, randomized Phase 3 study of erlotinib in combination with ramucirumab or placebo in previously untreated patie

19、nts with epidermal growth factor receptor mutation-positive metastatic non-small cell lung cancerPresented By Kazuhiko Nakagawa at 2019 ASCO Annual Meeting延緩耐藥：A+T28ASCO肺癌靶向治療新進(jìn)展10/2/2022RELAY: A multicenter, double-b1. Garon EB et al. Clin Lung Cancer 2017; 2. Reck M et al. Clin Lung Cancer 2018 Pr

20、esented By Kazuhiko Nakagawa at 2019 ASCO Annual MeetingRELAY研究：厄洛替尼聯(lián)合雷莫蘆單抗用于初治EGFR M+ NSCLC患者的多中心、雙盲、隨機(jī)對(duì)照3期研究29ASCO肺癌靶向治療新進(jìn)展10/2/20221. Garon EB et al. Clin Lung CSlide 8Presented By Kazuhiko Nakagawa at 2019 ASCO Annual MeetingPFS數(shù)據(jù)30ASCO肺癌靶向治療新進(jìn)展10/2/2022Slide 8Presented By Kazuhiko NSlide 13Pres

21、ented By Kazuhiko Nakagawa at 2019 ASCO Annual MeetingT790M耐藥占比31ASCO肺癌靶向治療新進(jìn)展10/2/2022Slide 13Presented By Kazuhiko 延緩耐藥：9291+AvastinORR: 80%PFS: 18.4N= 4932ASCO肺癌靶向治療新進(jìn)展10/2/2022延緩耐藥：9291+AvastinORR: 80%N= 49延緩耐藥：化療+TKIsJMIT33ASCO肺癌靶向治療新進(jìn)展10/2/2022延緩耐藥：化療+TKIsJMIT33ASCO肺癌靶向治療新進(jìn)Gefitinib versus gef

22、itinib-pemetrexed-carboplatin in EGFR mutated lung cancer (Gef vs. Gef + C)Presented By Vanita Noronha at 2019 ASCO Annual Meeting延緩耐藥：化療+TKI34ASCO肺癌靶向治療新進(jìn)展10/2/2022Gefitinib versus gefitinib-pem研究設(shè)計(jì)Presented By Vanita Noronha at 2019 ASCO Annual MeetingJ Clin Oncol 37, 2019 (suppl; abstr 9001)35ASC

23、O肺癌靶向治療新進(jìn)展10/2/2022研究設(shè)計(jì)Presented By Vanita Noronh療效數(shù)據(jù)36ASCO肺癌靶向治療新進(jìn)展10/2/2022療效數(shù)據(jù)36ASCO肺癌靶向治療新進(jìn)展10/1/2022NSCLC中的EGFR突變ASCO肺癌靶向治療新進(jìn)展EGF結(jié)合 EGF結(jié)合TM 酪氨酸激酶區(qū) 外顯子2 5 7 13 16 17 18-21 22-24 28688728729761762823824875外顯子18外顯子19外顯子20外顯子21Ex19DelL858RG719XL861QEx20 Ins3710/2/2022NSCLC中的EGFR突變ASCO肺癌靶向治療新進(jìn)展EGF結(jié)E

24、GFR-20外顯子插入突變: EGFR第一、二代TKIs均不敏感38ASCO肺癌靶向治療新進(jìn)展10/2/2022EGFR-20外顯子插入突變: EGFR第一、二代TKIs均39ASCO肺癌靶向治療新進(jìn)展10/2/202239ASCO肺癌靶向治療新進(jìn)展10/1/2022EGFR Exon 20 Insertions 肺癌： EGFR和cMET雙特異性抗體JNJ-372 ORR= 30%, N=2740ASCO肺癌靶向治療新進(jìn)展10/2/2022EGFR Exon 20 Insertions 肺癌： EGLung Cancer 127 (2019) 146152C225增加阿法替尼、AZD9291

25、的療效41ASCO肺癌靶向治療新進(jìn)展10/2/2022Lung Cancer 127 (2019) 146152新方案：阿法替尼+C225J Thorac Oncol. 20183/4 PR42ASCO肺癌靶向治療新進(jìn)展10/2/2022新方案：阿法替尼+C225J Thorac Oncol. 2研究方案IIIB或IV晚期NSCLC EGFR-20外顯子插入ECOG PS 0-1一線標(biāo)準(zhǔn)治療后A組: Afatinib: 30mg或AZD9291 C225：250mg/m2/兩周B組： Afatinib: 30mg或AZD9291 C225：500mg/m2/兩周主要研究終點(diǎn)：safety次要終

26、點(diǎn)：ORR，PFS，OS, Bio-markersC組： Afatinib: 40mg或AZD9291 C225：250mg/m2/兩周D組： Afatinib: 40mg或AZD9291 C225：500mg/m2/兩周N=3-12N=3-12N=3-12N=3-12Ib II IIIB或IV晚期NSCLC EGFR-20外顯子插入ECOG PS 0-1一線標(biāo)準(zhǔn)治療后A or B or C or D (Best) , N=60例主要研究終點(diǎn)：ORR次要終點(diǎn)：PFS，OS, Bio-markers注冊(cè)臨床研究43ASCO肺癌靶向治療新進(jìn)展10/2/2022研究方案IIIB或IV晚期NSCLC

27、A組: AfatinAntitumor activity of TAK-788 in NSCLC with EGFR exon 20 insertionsPresented By Pasi Janne at 2019 ASCO Annual MeetingEGFR Exon 20 Insertions 肺癌新藥：TAK78844ASCO肺癌靶向治療新進(jìn)展10/2/2022Antitumor activity of TAK-788 TAK-788 Antitumor Activity in Patients With EGFR Exon 20 InsertionsPresented By Pas

28、i Janne at 2019 ASCO Annual Meeting有效率：ORR=43%45ASCO肺癌靶向治療新進(jìn)展10/2/2022TAK-788 Antitumor Activity in TAK-788 Antitumor Activity in Patients With EGFR Exon 20 InsertionsPresented By Pasi Janne at 2019 ASCO Annual Meeting不用類型均有效46ASCO肺癌靶向治療新進(jìn)展10/2/2022TAK-788 Antitumor Activity in EGFR陽性肺癌新進(jìn)展： 現(xiàn)狀：三代同堂

29、未來：克服耐藥 (JNJ-372，U3-1402 聯(lián)合、IO+C) 延緩耐藥（A+T、化療聯(lián)合TKIs） EGFR-20插入：波奇替尼、TAK-788、 JNJ-372, C255+afatinib 47ASCO肺癌靶向治療新進(jìn)展10/2/2022EGFR陽性肺癌新進(jìn)展：47ASCO肺癌靶向治療新進(jìn)展10/主要內(nèi)容EGFR： 克服耐藥：JNJ-372，U3-1402， 延緩耐藥： RELAY研究，化療+TKI，9291+A EGFR-20插入： JNJ-372， TAK788K-RAS：AMG510，曲美替尼+多西他賽ALK：J-ALEX更新，Brigatinib 后線ROS1：Repotre

30、ctinibC-met：Tepotinib，CapmatinibRET：BLU-667Her-2：吡咯替尼B-raf: NTRKs：NCCN指南推薦檢測(cè)八個(gè)基因+K-RAS48ASCO肺癌靶向治療新進(jìn)展10/2/2022主要內(nèi)容EGFR：NCCN指南推薦檢測(cè)八個(gè)基因+K-RAS4Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics (PK) and Efficacy of AMG 510, a Novel Small Molecule KRASG12C Inhibitor, in Advanced Solid T

31、umors Presented By Marwan Fakih at 2019 ASCO Annual MeetingK-RAS 新藥：AMG 51049ASCO肺癌靶向治療新進(jìn)展10/2/2022Phase 1 Study Evaluating the SAMG 510 is a First in Class KRASG12C InhibitorPresented By Marwan Fakih at 2019 ASCO Annual MeetingK-RAS 新藥：AMG 51050ASCO肺癌靶向治療新進(jìn)展10/2/2022AMG 510 is a First in Class KRAM

32、G 510 First in Human Study DesignPresented By Marwan Fakih at 2019 ASCO Annual Meeting研究設(shè)計(jì)51ASCO肺癌靶向治療新進(jìn)展10/2/2022AMG 510 First in Human Study DPatient Incidence of Common (10%) and Serious Treatment Emergent Adverse Events (TEAE)Presented By Marwan Fakih at 2019 ASCO Annual Meeting安全性52ASCO肺癌靶向治療新進(jìn)

33、展10/2/2022Patient Incidence of Common (NSCLC: Best Tumor Response* (n=10)Presented By Marwan Fakih at 2019 ASCO Annual MeetingORR=50%NSCLC療效數(shù)據(jù)打響了肺癌K-ras單藥靶向治療的第一槍53ASCO肺癌靶向治療新進(jìn)展10/2/2022NSCLC: Best Tumor Response* (nCRC and Other Solid Tumors: Best Tumor Response* (n=19)Presented By Marwan Fakih at

34、2019 ASCO Annual Meeting腸癌及其他瘤種療效數(shù)據(jù)54ASCO肺癌靶向治療新進(jìn)展10/2/2022CRC and Other Solid Tumors: BeDuration of Treatment by Tumor Types and Responses (n=29)Presented By Marwan Fakih at 2019 ASCO Annual Meeting持續(xù)治療時(shí)間55ASCO肺癌靶向治療新進(jìn)展10/2/2022Duration of Treatment by TumorORR=33%ORR=26%ORR=37%(n=54)(n=19)(n=35)56

35、ASCO肺癌靶向治療新進(jìn)展10/2/2022ORR=33%ORR=26%ORR=37%(n=54)(n=主要內(nèi)容EGFR： 克服耐藥：JNJ-372，U3-1402， 延緩耐藥： RELAY研究，化療+TKI，9291+A EGFR-20插入： JNJ-372， TAK788K-RAS：AMG510，曲美替尼+多西他賽ALK：J-ALEX更新，Brigatinib 后線ROS1：RepotrectinibC-met：Tepotinib，CapmatinibRET：BLU-667Her-2：吡咯替尼B-raf: NTRKs：NCCN指南推薦檢測(cè)八個(gè)基因+K-RAS57ASCO肺癌靶向治療新進(jìn)展1

36、0/2/2022主要內(nèi)容EGFR：NCCN指南推薦檢測(cè)八個(gè)基因+K-RAS5阿來替尼在NSCLC的PFS創(chuàng)造了一個(gè)新的高峰34.858ASCO肺癌靶向治療新進(jìn)展10/2/2022阿來替尼在NSCLC的PFS創(chuàng)造了一個(gè)新的高峰34.858A阿來替尼 300mg BID每28天一個(gè)周期n=103克唑替尼 250mg BID每28天一個(gè)周期n=104R1:1IIIB/IV期 NSCLC經(jīng)IHC、FISH 或 RT-PCR檢測(cè)確診為ALK+ 腫瘤未接受過化療 或 接受過一線化療未接受過ALK抑制劑治療ECOG PS 02（n=207）J-ALAX研究數(shù)據(jù)更新：PFS：34.1 MLancet 2017

37、; 390: 29392019ASCO-909259ASCO肺癌靶向治療新進(jìn)展10/2/2022阿來替尼 300mg BID每28天一個(gè)周期n=103克Brigatinib 后線療效數(shù)據(jù)至少一個(gè)二代ALK抑制劑后 接受至少兩個(gè)ALK抑制劑后ORR=40%ORR=50%PFS=6.4MPFS=6.6MAbstract ID：9027Abstract ID：904560ASCO肺癌靶向治療新進(jìn)展10/2/2022Brigatinib 后線療效數(shù)據(jù)至少一個(gè)二代ALK抑制劑后主要內(nèi)容EGFR： 克服耐藥：JNJ-372，U3-1402， 延緩耐藥： RELAY研究，化療+TKI，9291+A EGFR

38、-20插入： JNJ-372， TAK788K-RAS：AMG510，曲美替尼+多西他賽ALK：J-ALEX更新，Brigatinib 后線ROS1：RepotrectinibC-met：Tepotinib，CapmatinibRET：BLU-667Her-2：吡咯替尼B-raf: NTRKs：NCCN指南推薦檢測(cè)八個(gè)基因+K-RAS61ASCO肺癌靶向治療新進(jìn)展10/2/2022主要內(nèi)容EGFR：NCCN指南推薦檢測(cè)八個(gè)基因+K-RAS6ROS1 inhibitors in TKI naive patientsPresented By Benjamin Besse at 2019 ASCO

39、Annual Meeting（洛普替尼）（恩曲替尼）62ASCO肺癌靶向治療新進(jìn)展10/2/2022ROS1 inhibitors in TKI naive pROS1 inhibitors in TKI pretreated patientsPresented By Benjamin Besse at 2019 ASCO Annual Meeting63ASCO肺癌靶向治療新進(jìn)展10/2/2022ROS1 inhibitors in TKI pretreaROS1 inhibitorsPresented By Benjamin Besse at 2019 ASCO Annual Meetin

40、g64ASCO肺癌靶向治療新進(jìn)展10/2/2022ROS1 inhibitorsPresented By Be主要內(nèi)容EGFR： 克服耐藥：JNJ-372，U3-1402， 延緩耐藥： RELAY研究，化療+TKI，9291+A EGFR-20插入： JNJ-372， TAK788K-RAS：AMG510，曲美替尼+多西他賽ALK：J-ALEX更新，Brigatinib 后線ROS1：RepotrectinibC-met：Tepotinib，CapmatinibRET：BLU-667Her-2：吡咯替尼B-raf: NTRKs：NCCN指南推薦檢測(cè)八個(gè)基因+K-RAS65ASCO肺癌靶向治療新

41、進(jìn)展10/2/2022主要內(nèi)容EGFR：NCCN指南推薦檢測(cè)八個(gè)基因+K-RAS6Paik Cancer Discovery 2015 * Tong - Clin Cancer Res 2016.Drilon A et al, J Thoracic Oncol, 2016.C-met異常肺癌66ASCO肺癌靶向治療新進(jìn)展10/2/2022Paik Cancer Discovery 2015 *C-met異常肺癌：第1類MET抑制劑Cui JJ, et al, J Med Chem. 2011 Sep 22;54(18):6342-63; Bladt F, et al, Clin Cancer

42、Res. 2013 Jun 1;19(11):2941-51.(INC280)（特泊替尼）67ASCO肺癌靶向治療新進(jìn)展10/2/2022C-met異常肺癌：第1類MET抑制劑Cui JJ, et C-met擴(kuò)增肺癌：克唑替尼、Capmatinib68ASCO肺癌靶向治療新進(jìn)展10/2/2022C-met擴(kuò)增肺癌：克唑替尼、Capmatinib68ASCC-met-14skipping肺癌：克唑替尼69ASCO肺癌靶向治療新進(jìn)展10/2/2022C-met-14skipping肺癌：克唑替尼69ASCO肺Capmatinib in METex14-mutated advanced non-sm

43、all cell lung cancer (NSCLC): Efficacy data from the phase II GEOMETRY mono-1 studyPresented By Juergen Wolf at 2019 ASCO Annual Meeting70ASCO肺癌靶向治療新進(jìn)展10/2/2022Capmatinib in METex14-mutatedGEOMETRY mono-1: A phase II trial of capmatinib in patients with advanced NSCLC harboring MET exon14 skipping m

44、utationPresented By Juergen Wolf at 2019 ASCO Annual Meeting71ASCO肺癌靶向治療新進(jìn)展10/2/2022GEOMETRY mono-1: A phase II tr Best overall response (pretreated cohort 4)Presented By Juergen Wolf at 2019 ASCO Annual Meeting72ASCO肺癌靶向治療新進(jìn)展10/2/2022 Best overall response (pretreBest overall response (treatment na

45、ive cohort 5b)Presented By Juergen Wolf at 2019 ASCO Annual Meeting73ASCO肺癌靶向治療新進(jìn)展10/2/2022Best overall response (treatmeTumor shrinkage per BIRCPresented By Juergen Wolf at 2019 ASCO Annual Meeting74ASCO肺癌靶向治療新進(jìn)展10/2/2022Tumor shrinkage per BIRCPresenProgression-free survival per BIRCPresented By J

46、uergen Wolf at 2019 ASCO Annual Meeting75ASCO肺癌靶向治療新進(jìn)展10/2/2022Progression-free survival per Conclusions Presented By Juergen Wolf at 2019 ASCO Annual Meeting反應(yīng)率：54%;7/13；4例CR76ASCO肺癌靶向治療新進(jìn)展10/2/2022Conclusions Presented By JuergPhase II study of tepotinib in NSCLC patients with METex14 mutations Pr

47、esented By Paul Paik at 2019 ASCO Annual Meeting77ASCO肺癌靶向治療新進(jìn)展10/2/2022Phase II study of tepotinib inVISION study designPresented By Paul Paik at 2019 ASCO Annual Meeting研究設(shè)計(jì)78ASCO肺癌靶向治療新進(jìn)展10/2/2022VISION study designPresented BEfficacy: Best overall response (IRC/Investigator) Presented By Paul Pa

48、ik at 2019 ASCO Annual Meeting客觀有效率79ASCO肺癌靶向治療新進(jìn)展10/2/2022Efficacy: Best overall responsEfficacy: Tumor shrinkage by line of therapyPresented By Paul Paik at 2019 ASCO Annual Meeting療效數(shù)據(jù)80ASCO肺癌靶向治療新進(jìn)展10/2/2022Efficacy: Tumor shrinkage by lEfficacy: Progression-free survivalPresented By Paul Paik a

49、t 2019 ASCO Annual MeetingPFS數(shù)據(jù)81ASCO肺癌靶向治療新進(jìn)展10/2/2022Efficacy: Progression-free sur主要內(nèi)容EGFR： 克服耐藥：JNJ-372，U3-1402， 延緩耐藥： RELAY研究，化療+TKI，9291+A EGFR-20插入： JNJ-372， TAK788K-RAS：AMG510，曲美替尼+多西他賽ALK：J-ALEX更新，Brigatinib 后線ROS1：RepotrectinibC-met：Tepotinib，CapmatinibRET：BLU-667Her-2：吡咯替尼B-raf: NTRKs：NCC

50、N指南推薦檢測(cè)八個(gè)基因+K-RAS82ASCO肺癌靶向治療新進(jìn)展10/2/2022主要內(nèi)容EGFR：NCCN指南推薦檢測(cè)八個(gè)基因+K-RAS8 NATURE REVIEWS | CLINICAL ONCOLOGY VOLUME 15 | MARCH 2018 | 151 RET陽性肺癌：凡德他尼、卡博替尼、LOXO-29283ASCO肺癌靶向治療新進(jìn)展10/2/2022RET陽性肺癌：凡德他尼、卡博替尼、LOXO-29283ASBLU-667 Demonstrates Substantial Antitumor Activity in RET Fusion+ Advanced NSCLCPre

51、sented By Justin Gainor at 2019 ASCO Annual MeetingRET融合肺癌：BLU-667ORR=71%84ASCO肺癌靶向治療新進(jìn)展10/2/2022BLU-667 Demonstrates Substanti研究藥物人數(shù)反應(yīng)率無進(jìn)展生存PFSDrilon A, 2016卡博替尼2528%未達(dá)到Lin JJ, 2016艾樂替尼450%治療反應(yīng)持續(xù)時(shí)間：6個(gè)月Lee SH, 2017凡德他尼1818%4.5 m.Yoh, K, 2017凡德他尼1953%4.7 m.Velcheti, 2016樂伐替尼2518%7.3 m.Gaustchi O, 2017不同注冊(cè)中心藥物不同5318 to 37%2.3 m.Subbiah V, 2018 (ASCO)凡德他尼 + 依維莫司1354% (7/13)4