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1、2022 年 12 月 9 日(星期五)行业报告 招商证券(香港)有限公司 证券研究部 此为2022年12月9日“China Pharmaceutical&Healthcare ASH 2022 data readout review”的中文摘要 1 中国医药、医疗行业中国医药、医疗行业 2022年年ASH血液学会议数据读出血液学会议数据读出总结总结 2022 ASH 血液学年度学术会议将于血液学年度学术会议将于12月月10-13日在美国新奥尔良召开日在美国新奥尔良召开 双特异性双特异性T细胞接细胞接合合抗体抗体(BiTEs)在多发性骨髓瘤领域)在多发性骨髓瘤领域进一步取得进一步取得进进展,创
2、新展,创新CAR-T/NK细胞工程技术展示出新的细胞工程技术展示出新的治疗潜力治疗潜力 我们继续战略性地推荐增持中国医药医疗行业中的生物医药子版块。行我们继续战略性地推荐增持中国医药医疗行业中的生物医药子版块。行业首选推荐为百济神州(业首选推荐为百济神州(BGNE US)基于公司具有实力的管线布局基于公司具有实力的管线布局 2022 ASH大会全球管线资产数据读出大会全球管线资产数据读出 关键数据读出:关键数据读出:1)BiTEs类候选药物针对治疗后线类候选药物针对治疗后线r/r MM取得进一步进展:取得进一步进展:Johson的双特异性T细胞接合抗体(BiTEs)teclistamab于今年
3、10月份首次获得批准后,BiTEs类候选药物在2022年ASH大会上治疗复发难治多发性骨髓瘤(r/r MM)领域取得进一步研发进展。其中Pfizer的elranatamab(BCMA x CD3 BiTE)在Ph2 Magnetismm-3 试验(NCT04649359,n=123)中,ORR为61%;Regeneron的linvoseltamab(REGN5458)在Ph1/2试验(NCT03761108,n=167)中ORR读出为75%,以及Johson具有新型靶点的 双 抗talquetamab(GPRC5D x CD3),在Ph1/2 MonumenTAL-1试 验(NCT033997
4、99/NCT04634552,n=288)中ORR读出为73%。Amgen/BeiGene的Blinatumomab(CD3 x CD19 BiTE)对比标准疗法用于治疗一线急性淋巴细胞白血病(ALL)显示OS获益(NR vs.SoCs 71.4 mo,HR 0.42,p=0.003)(摘要编号LBA-1)。另外,Affimed的NK细胞结合抗体AFM13(CD30 x CD16A BiTE)基于在体内与同种异体NK细胞形成CAR-NK预复合物,用于治疗复发难治霍奇金淋巴瘤(r/r/HL)显示 97%ORR(71%CR)。2)创新细胞治疗技术研发进展亮眼:)创新细胞治疗技术研发进展亮眼:Nov
5、artis的YTB323(CD19 CAR-T)以及Gracell的GC012F(BCMA x CD19 Car-T)主要专注于在缩短生产时间(2天)的同时,也保证临床疗效获益方面能够具有竞争优势。对于异体CAR-T研发方面,Adicet的 ADI-001(CD20 CAR-T)在治疗淋巴瘤方面显示出持续疗效(7/9 CRs,1例新复发)。Fate的FT576(BCMA CAR-NK)以及CRISPR的CTX110(CD19 allo CAR-T)显示出积极的早期安全性数据。除了BCMA类候选药物以外,BMS的BMS-986393(GPRC5D CAR-T)在针对经过BCMA治疗的Ph1试验中
6、首次读出临床数据(86%ORR并且安全性良好)。3)急性髓细胞性白血病领域竞争持续:)急性髓细胞性白血病领域竞争持续:我们注意到超过50%的研究摘要聚焦白血病领域,大多数为联合治疗研究,其中Ventoclax/azacitidine是在靶向治疗急性髓细胞性白血病(AML)领域常用的用药选择,例如联合CD47类(Gilead的magrolimab,ALXO的evopacept),Flt3抑 制 剂(Astellas的gilteritinib),以及IDH2抑制剂(BMSs enasidenib)。与此同时,临床上用于治 疗AML的 其 他 新 型 抑 制 剂 也 取 得 进 展。例 如Synda
7、x的revumenib(ORR=53%)和Kura的Ziftomenib(ORR=41.7%)都属于menin/MLL抑制剂,用于治疗KMT2Ar/NPM1m r/r AML并读出积极数据。以及Forma的Olutasidenib(IDH1抑制剂)用于治疗高风险mIDH1 AML。百济神州在百济神州在ASH大会上显示强势管线布局大会上显示强势管线布局 今年的ASH大会上,中国生物医药公司共发布了约80余个摘要,其中百济神州的 核 心 管 线 产 品(例 如zanubrutinib,tislelizumab,BGB-11417和 blinatumomab)发 表 了 约20多 个 摘 要。其 中
8、,百 济 神 州 有2个 产 品,zanubrutinib(在ALPINE头 对 头 对 照ibrutinib的Ph3试 验 中 用 于 治 疗CLL/SLL,读出PFS数据)以及 blinatumomab(ECOG-ACRIN E1910 Ph3试验读出OS数据)入围LBA重磅研究报告(共6个),反应公司在血液肿瘤领域的强势管线布局。投资风险:投资风险:临床资产的临床失效;数据差于预期;监管延误 张皓渊,CFA 余婉佳,PhD+852 3189 6354 .hk+852 3189 6268 .hk 代方琦,CFA +852 3189 6126 .hk 最新变动最新变动 第64届ASH美国血液
9、学会年会更新 推荐 前次评级 推荐 恒生指数(2022年12月09日)19,901 国企指数(2022年12月09日)6,834 行业表现 资料来源:彭博%1m 6m 12m 绝对回报 5.8(14.9)(50.8)相对回报 (8.9)(2.6)(28.3)相关报告相关报告 1.中国医药、医疗行业 11月份数据显示投融资仍然疲弱(推荐)(2022/12/02)2.中国医药、医疗行业 研发洞察003期:CAR-T细胞治疗概览(推荐)(2022/11/21)3.中国医药、医疗行业 2022年ESMO总结-肿瘤免疫学领域研究进展丰富(推荐)(2022/9/19)4.中国医药、医疗行业 2022年 E
10、SMO会议预览 聚焦 KRAS(推荐)(2022/9/7)-50%-40%-30%-20%-10%0%10%医药医疗恒生指数2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 2 报告内容报告内容 LBA 重磅研究数据读出重磅研究数据读出.3 多发性骨髓瘤多发性骨髓瘤 研究进展研究进展.4 白血病白血病 研究进展研究进展.7 淋巴瘤淋巴瘤 研究进展研究进展.12 创新治疗技术创新治疗技术 CAR-T 细胞细胞治疗研究进展治疗研究进展.15 附录附录 A:FDA 批准用于治疗血液肿瘤的药品批准用于治疗血液肿瘤的药品.17 附录附录 B:NCCN 推荐血液肿瘤用药指南推荐血液肿
11、瘤用药指南.19 附录附录 C:主要管线产品主要管线产品及销售预测及销售预测.22 附录附录 D:参考文献参考文献.24 投资风险投资风险.25 分析师声明分析师声明.26 监管披露监管披露.26 免责条款免责条款.26 图 1:ASH 2022 重磅研究数据读出.3 图 2:ASH 2022 重磅研究数据读出 多发性骨髓瘤.4 图 3:ASH 2022 重磅研究数据读出 白血病.7 图 4:ASH 2022 重磅研究数据读出 淋巴瘤.12 图 5:ASH 2022 研究数据读出 CAR-T 细胞治疗.15 AVhVbWqUlWnVsQmOpNaQcM8OtRoOmOmOlOmNoMkPmNm
12、O7NqRmMNZmPqMwMnMsN2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 3 LBA重磅研究数据读出重磅研究数据读出 LBA 重磅重磅研究展示前沿进展:研究展示前沿进展:ASH 2022 一共收录了 6 项 LBA 重磅研究,这些研究进展可能在血液肿瘤领域带来具有变革性的治疗获益,其中我们注意到 Amgen/Beigene的的 Blinatumomab(CD3 x CD19 BsAb)显示显著 OS 获益,展示了在治疗 ALL 方向上成为新标准疗法的潜力(LBA-1);同时,Beigene 的的 Zanubrutinib(BTKi)相比较第一代 BTKi 在
13、 ORR 和 PFS 读出方面展示出优越性(LBA-6)。图1:ASH 2022 重磅研究数据读出 No.公司公司 通用名通用名(商品名商品名)靶点靶点 分子类型分子类型 适应症适应症 临床阶段临床阶段(#入组人数入组人数)实验名称实验名称(NCT ID)治疗方案治疗方案 ORR (%)CR(%)mPFS (mos)mOS (mos)随访时间随访时间(mos)摘要题目摘要题目 LBA-1 Amgen/Astella/BeiGene Blinatumomab(Blincyto)CD3 x CD19 BsAb 1L ALL Ph3(n=722)ECOG-ACRIN E1910(NCT0200322
14、2)81%not reached v.s 71 mos 43 Consolidation Therapy with Blinatumomab Improves Overall Survival in Newly Diagnosed Adult Patients with B-Lineage Acute Lymphoblastic Leukemia in Measurable Residual Disease Negative Remission:Results from the ECOG-ACRIN E1910 Randomized Phase III National Cooperative
15、 Clinical Trials Network Trial LBA-2 Novartis Iptacopan Factor B SMD PNH,Anemia Ph3(n=97)Apply PNH IPT v.s SoC Oral Monotherapy with Iptacopan,a Proximal Complement Inhibitor of Factor B,Has Superior Efficacy to Intravenous Terminal Complement Inhibition with Standard of Care Eculizumab or Ravulizum
16、ab and Favorable Safety in Patients with Paroxysmal Nocturnal Hemoglobinuria and Residual Anemia:Results from the Randomized,Active-Comparator-Controlled,Open-Label,Multicenter,Phase III Apply-PNH Study LBA-3 University of Freiburg et al HDC-ASCT n.a Cell therapy CNS lymphoma Ph3(n=260)MATRix/IELSG4
17、3(NCT02531841)Consolidation therapy(HDC-ASCT v.s R-DEVIC)52%3 yr PFS:79%v.s 53%3 yr OS:86%v.s 71%44 Effects on Survival of Non-Myeloablative Chemoimmunotherapy Compared to High-Dose Chemotherapy Followed By Autologous Stem Cell Transplantation(HDC-ASCT)As Consolidation Therapy in Patients with Prima
18、ry CNS Lymphoma-Results of an International Randomized Phase III Trial(MATRix/IELSG43)LBA-4 Univeristy of Minnesota et al alloHCT n.a Cell therapy GVHD disease relapse Ph3(n=128)BMT CTN 1703 PTCy v.s Tac/MTX No significant difference Post-Transplant Cyclophosphamide,Tacrolimus,and Mycophenolate Mofe
19、til As the New Standard for Graft-Versus-Host Disease(GVHD)Prophylaxis in Reduced Intensity Conditioning:Results from Phase III BMT CTN 1703 LBA-5 University of Warwick et al Heparin n.a SMD R/R ALIFE2 Ph3(n=428)LMWH v.s SoC live birth rate:71.6%v.s 70.9%Low-Molecular-Weight Heparin Versus Standard
20、Pregnancy Care for Women with Recurrent Miscarriage and Inherited Thrombophilia(ALIFE2):An Open-Label,Phase III Randomized Controlled Trial()LBA-6 BeiGene Zanubrutinib(Brukinsa)BTK SMD R/R CLL/SLL Ph3(n=652)ALPINE(NCT03734016)Zanu v.s Ibru 86.2 vs 75.7%,P=0.0007 NR vs.35mo P=0.0024 29.6 Zanubrutinib
21、 Demonstrates Superior Progression-Free Survival(PFS)Compared with Ibrutinib for Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma(R/R CLL/SLL):Results from Final Analysis of ALPINE Randomized Phase 3 Study 资料来源:招商证券(香港),ASH 2022 2022 年 12 月 9 日(星期五)彭博终端报告下
22、载:NH CMS 4 多发性骨髓瘤多发性骨髓瘤 研究研究进展进展 多 发 性 骨 髓 瘤 前 沿 研 究 进 展多 发 性 骨 髓 瘤 前 沿 研 究 进 展:1)双 抗 领 域 取 得 进 一 步 进 展)双 抗 领 域 取 得 进 一 步 进 展:继 Johnson 的 teclistamab 于 2022 年 10 月 25 日 基 于 MajesTEC-1 试 验(n=165,NCT03145181/NCT04557098,ORR=62%)首次获得 FDA 批准后,双抗在 r/r MM 治疗领域进一步取得进展。其中我们注意到以下资产读出优秀数据:Pfizer 的elranatamab(
23、BCMA x CD3 BsAb)在 Ph2 Magnetismm-3 试验中(NCT04649359,n=123)ORR 读出 61%,Regeneron 的 linvoseltamab 在 Ph1/2 试验中(NCT03761108,n=167)ORR 读出 75%,以及 Johnson 的具有新靶点的双抗 alquetamab(GPRC5D x CD3 BsAb)在 Ph1/2 MonumenTAL-1 试验(NCT03399799/NCT04634552,n=288)中,ORR 读出为 73%。2)CAR-NK 展示早期研究进展:展示早期研究进展:除了 BCMA 靶向 CAR-T 细胞治
24、疗以外,我们注意到 Fate Therapeutics 的 FT576 采用可再生多全能干细胞技术为制备“现成产品”提供可能性。与此同时,在 Ph1 试验中所采用的两种剂量(100m 或 300m 细胞/每剂量),没有 CRS,NT,或 GvHD 报道。尽管还在早期,NK 细胞由于取材方便(例如,取自 iPSC 或 NK 细胞系),和安全性更佳等优势成为下一个研发的方向。3)GPRC5D 作为新型靶点:作为新型靶点:经过检测原代骨髓样本,GPRC5D(class C group 5 member D)蛋白以独立于 BCMA 的方式在 CD138+MM 细胞中有表达3。我们注意到在该靶点上的早期
25、临床试验读出具有潜力的数据,其中 Johnson 的 alquetamab(GPRC5D x CD3 BsAb)在 Ph1/2 MonumenTAL-1 试验(NCT03399799/NCT04634552,n=288)中 ORR 读出 73%,BMS 的 BMS-986393,GPRC5D 靶向 CAR-T 疗法,在14 个入组病人中读出高有效性(ORR 读出 86%)。除此之外,在经过前线 BCMA 靶向治疗的病人(其中 4/5 mAb,3/5 CAR-T)种显示有效性。4)CD38 单抗聚焦早期治疗:单抗聚焦早期治疗:Johnso 的 daratumumab,根据 NCCN 治疗目前用于
26、一线 MM,在第三期 IFM2017-03 试验中(n=259,NCT03993912).ORR 读出为 89%。除此之外,Sanofi 的isatuximab 在 Ph3 ITHACA 试验中(n=23),用于治疗 SMM(ORR 读出为 100%)。图2:ASH 2022 重磅研究数据读出 多发性骨髓瘤 公司公司 通用名通用名 靶点靶点 分子类型分子类型 临床阶段临床阶段 适应症适应症 ORR (%),CR(%)试验名称试验名称 入组人数入组人数 NCT ID 摘要题目摘要题目 GSK,Seagen belantamab mafodotin BCMA ADC Ph 2 1L MM ORR:
27、82.1%GEM-BELA-VRd 40 NCT04802356 Belantamab Mafodotin in Combination with Vrd for the Treatment of Newly Diagnosed Transplant Eligible Multiple Myeloma Patients:Results from the Phase II,Open Label,Multicenter,GEM-BELA-Vrd Trial CARsgen zevorcabtagene autoleucel BCMA CAR-T Ph 2 r/r MM ORR:92.8%CR/sC
28、R:42.2%LUMMICAR STUDY 1 102 NCT03975907 Phase II Study of Fully Human BCMA-Targeting CAR-T Cells(Zevorcabtagene Autoleucel)in Patients with Relapsed/Refractory Multiple Myeloma BMS,Celgene idecabtagene vicleucel BCMA CAR-T Ph 2 MM ORR:83.8%CR:45.9%KarMMa-2 39 NCT03601078 KarMMa-2 Cohort 2a:Efficacy
29、and Safety of Idecabtagene Vicleucel in Clinical High-Risk Multiple Myeloma Patients with Early Relapse after Frontline Autologous Stem Cell Transplantation BMS,Celgene idecabtagene vicleucel BCMA CAR-T Ph 2 MM ORR:87.1%KarMMa-2 32 NCT03601078 KarMMa-2 Cohort 2c:Efficacy and Safety of Idecabtagene V
30、icleucel in Patients with Clinical High-Risk Multiple Myeloma Due to Inadequate Response to Frontline Autologous Stem Cell Transplantation 2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 5 公司公司 通用名通用名 靶点靶点 分子类型分子类型 临床阶段临床阶段 适应症适应症 ORR (%),CR(%)试验名称试验名称 入组人数入组人数 NCT ID 摘要题目摘要题目 Fate therapeutics FT579 BCMA CAR-N
31、K Ph 1 r/r MM*No G3 CRS,NT n.a n.a 9 n.a Interim Phase I Clinical Data of FT576 As Monotherapy and in Combination with Daratumumab in Subjects with Relapsed/Refractory Multiple Myeloma Allogene ALLO-715 BCMA CAR-T Ph 1 3L r/r MM ORR:80%CR:27%UNIVERSAL 53 NCT04093596 Universal Updated Phase 1 Data Hi
32、ghlights Role of Allogeneic Anti-BCMA ALLO-715 Therapy for Relapsed/Refractory Multiple Myeloma Arcellx CART-Ddbcma BCMA CAR-T Ph 1 r/r MM ORR:100%CR:71%n.a 37 n.a Phase 1 Study of CART-Ddbcma for the Treatment of Subjects with Relapsed and/or Refractory Multiple Myeloma Gracell GC012F BCMA CAR-T Ph
33、 1 1L MM ORR:100%CR:69%n.a 13 NCT04935580 Phase I Open-Label Single-Arm Study of BCMA/CD19 Dual-Targeting FasTCAR-T Cells(GC012F)As First-Line Therapy for Transplant-Eligible Newly Diagnosed High-Risk Multiple Myeloma Pfizer elranatamab BCMA x CD3 BsAb Ph 2 r/r MM ORR:61%n.a Magnetismm-3 123 NCT0464
34、9359 Efficacy and Safety of Elranatamab in Patients with Relapsed/Refractory Multiple Myeloma Nave to B-Cell Maturation Antigen(BCMA)-Directed Therapies:Results from Cohort a of the Magnetismm-3 Study Regeneron linvoseltamab BCMA x CD3 BsAb Ph 1/2 r/r MM ORR:75%n.a n.a 167 NCT03761108 Updated Safety
35、 and Efficacy of REGN5458,a BCMAxCD3 Bispecific Antibody,Treatment for Relapsed/Refractory Multiple Myeloma:A Phase 1/2 First-in-Human Study Abbive HPN217 BCMA x CD3 x albumin TsAb Ph 1 r/r MM*No G3 CRS n.a n.a 49 NCT04184050 Updated Interim Results from a Phase 1 Study of HPN217,a Half-Life Extende
36、d Tri-Specific T Cell Activating Construct(TriTAC)Targeting B Cell Maturation Antigen(BCMA)for Relapsed/Refractory Multiple Myeloma(RRMM)Pfizer elranatamab BCMA x CD3 BsAb Ph 3 r/r MM MagnetisMM-5 28 NCT05020236 Elranatamab in Combination with Daratumumab for Patients(pts)with Relapsed/Refractory Mu
37、ltiple Myeloma(RRMM):Results from the Phase 3 Magnetismm-5 Study Safety Lead-in Cohort Johnson&Johnson daratumumab CD38 mAb Ph 2 r/r MM ORR:60%Dedalo 45 NCT04124497 Dedalo:Phase II Study of Daratumumab Plus Pomalidomide and Dexamethasone(DPd)in Patients with Relapsed/Refractory Multiple Myeloma and
38、17p Deletion Sanofi isatuximab CD38 mAb Ph 3 SMM ORR:100%CR:30.4%ITHACA 23 NCT04270409 Isatuximab in Combination with Lenalidomide and Dexamethasone in Patients with High-Risk Smoldering Multiple Myeloma:Updated Safety Run-in Results from the Randomized Phase 3 Ithaca Study Johnson&Johnson daratumum
39、ab CD38 mAb Ph 3 1L MM ORR:68%MAXDARA 24 NCT03792620 Daratumumab(Dara),Cyclophosphamide,Thalidomide and Dexamethasone for Transplant Eligible Newly Diagnosed Multiple Myeloma(TE NDMM)Patients:Response Rate Impacts on PFS 2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 6 公司公司 通用名通用名 靶点靶点 分子类型分子类型 临床阶段临床阶段 适应症适应症
40、 ORR (%),CR(%)试验名称试验名称 入组人数入组人数 NCT ID 摘要题目摘要题目 Johnson&Johnson daratumumab CD38 mAb Ph 3 1L MM ORR:89%vs.77%IFM2017-03 295 NCT03993912 A Dexamethasone Sparing-Regimen with Daratumumab and Lenalidomide in Frail Patients with Newly-Diagnosed Multiple Myeloma:Efficacy and Safety Analysis of the Phase
41、3 IFM2017-03 Trial Johnson&Johnson daratumumab CD38 mAb Ph 2 1L MM ORR:95%25 NCT04151667 Daratumumab Based Response Adapted Therapy for Older Adults with Newly Diagnosed Multiple Myeloma:Interim Analysis of Phase II Study JOHSON,Takerda daratumumab;ixazomib CD38 mAb,SMD Ph 2 2L MM ORR:83%37 NCT03590
42、652 Phase II Study of the Combination of Daratumumab,Ixazomib,Pomalidomide,and Dexamethasone in Early Relapsed/Refractory Multiple Myeloma Sanofi isatuximab CD38 mAb Ph 2 1L MM ORR:100%SKylaRk 50 NCT04430894 A Phase II Study of Once Weekly Carfilzomib,Lenalidomide,Dexamethasone,and Isatuximab in New
43、ly Diagnosed,Transplant-Eligible Multiple Myeloma(The SKylaRk Trial)Bristol Myers Squibb BMS-986393 GPRC5D CAR-T Ph 1 r/r MM ORR:86%n.a n.a 21 NCT04674813 Clinical Activity of BMS-986393(CC-95266),a G ProteinCoupled Receptor Class C Group 5 Member D(GPRC5D)Targeted Chimeric Antigen Receptor(CAR)T Ce
44、ll Therapy,in Patients with Relapsed and/or Refractory(R/R)Multiple Myeloma(MM):First Results from a Phase 1,Multicenter,Open-Label Study Johnson&Johnson Talquetamab GPRC5D x CD3 BsAb Ph 1/2 r/r MM ORR:73%CR:29%MonumenTAL-1 288 NCT03399799/NCT04634552 Talquetamab,a G Protein-Coupled Receptor Family
45、C Group 5 Member D x CD3 Bispecific Antibody,in Patients with Relapsed/Refractory Multiple Myeloma(RRMM):Phase 1/2 Results from MonumenTAL-1 Takeda ixazomib protease SMD Ph 2 MM ORR:65%vs 42%IRB00077815 42 NCT02765854 Phase II Trial of Ixazomib and Dexamethasone Versus Ixazomib,Dexamethasone and Len
46、alidomide,Randomized with NFKB2 Rearrangement.(Proteasome Inhibitor NFKB2 Rearrangement Driven Trial,PINR)Roche RG6234 GPRC5DxCD3 BsAb Ph 1 r/r MM*G3 CRS IV:2%;SC:1.9%n.a n.a 51 NCT04557150 RG6234,a GPRC5DxCD3 T-Cell Engaging Bispecific Antibody,Is Highly Active in Patients(pts)with Relapsed/Refract
47、ory Multiple Myeloma(RRMM):Updated Intravenous(IV)and First Subcutaneous(SC)Results from a Phase I Dose-Escalation Study Celgene,BMS mezigdomide IKZF3,IKZF1,CRBN SMD Ph 2 r/r MM ORR:39.6%CC-92480-MM-001 101 NCT03374085 Mezigdomide(CC-92480),a Potent,Novel Cereblon E3 Ligase Modulator(CELMoD),Combine
48、d with Dexamethasone(DEX)in Patients(pts)with Relapsed/Refractory Multiple Myeloma(RRMM):Preliminary Results from the Dose-Expansion Phase of the CC-92480-MM-001 Trial Beigene carfilzomib;daratumumab Protease,CD38 mAb Ph 2 1L MM n.a CR/sCR:65.2%n.a 30 NCT04113018 Interim Results of a Risk-Adaptive P
49、hase II Study:Carfilzomib,Lenalidomide,Dexamethasone and Daratumumab(KRD-Dara)in Newly Diagnosed Multiple Myeloma(NDMM)at the Levine Cancer Institute(LCI)资料来源:招商证券(香港),ASH 2022,灰色,重点关注研究 2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 7 白血病白血病 研究研究进展进展 白血病前沿研究进展白血病前沿研究进展:1)关注)关注 KMT2Ar/NPM1m 基因型:基因型:KMT2Ar 和 NP
50、M1m(即 KMT2A 重排、NPM1 突变)分别发生在约 5-10%和 30%的急性髓细胞性白血病(AML)中,并可导致白血病发生。靶向 menin 的抑制剂破坏 KMT2A 相关蛋白复合物,为 KMT2Ar/NPM1m r/r AML 的治疗提供治疗思路5-6。我们注意到 Syndax 的 revumenib(ORR=53%)以及 Kura 的 Ziftomenib(ORR=41.7%)在用于治疗 KMT2Ar/NPM1m r/r AML 方面取得积极数据。其他的用于治疗突变型 AML 的候选药物包括 BMS 的azacitidine(DNMT,DNA 甲基转移酶抑制剂用于 KMT2Ar
51、r/r AML,以及 Forma 的 Olutasidenib(IDH1 抑制剂)用于治疗高风险 mIDH1 AML,以及 Novartis 的 ruxolitinib(JAK1/2 抑制剂)用于治疗 CRLF2r Ph-like ALL.2)免疫疗法应用在前后线治疗中:)免疫疗法应用在前后线治疗中:除了 ADCs(例如,Pfizer 的 CD22 ADC Besponsa)在一线 ALL 治疗领域取得进展,CAR-T 治疗读出高有效性(例如,JW theraputics 的 relma-cel)用于治疗三线 MCL,Astellas/Amgen/Beigene 的 CD3 x CD19 Bs
52、Ab 在 Ph3 试验(NCT04994717,NCT02003222)中用于治疗一线 ALL 读出丰富数据,显示治疗和生存获益。图3:ASH 2022 重磅研究数据读出 白血病 公司公司 通用名通用名 靶点靶点 分子类型分子类型 临床阶段临床阶段 适应症适应症 ORR(%)CR(%)mPFS,mOS(mos)实验名称实验名称 入组人数入组人数 NCT ID 摘要题目摘要题目 Hansoh flumatinib Bcr-Abl SMD Ph 2 1L ALL CR:93.2%RJ-ALL2020.2A 44 ChiCTR2100042248 A Phase II Study of Flumat
53、inib with Chemotherapy for Newly Diagnosed Ph/BCR-ABL1-Positive Acute Lymphoblastic Leukemia in Adults:Preliminary Results from RJ-ALL2020.2A Trial Pfizer inotuzumab ozogamicin CD22 ADC Ph 2 1L ALL CR/CRp:90%EWALL-INO 131 NCT03249870 Fractionated Inotuzumab Ozogamicin Combined with Low-Intensity Che
54、motherapy in Older Patients with Newly Diagnosed CD22+Philadelphia Chromosome(Ph)-Negative B-Cell Precursor(BCP)Acute Lymphoblastic Leukemia(ALL):Results of the EWALL-INO Study Amgen/Astellas/BeiGene blinatumomab CD3 x CD19 BsAb Ph 3 1L PH-ve ALL CR:100%10 NCT04994717 Blinatumomab Alternating With L
55、ow-Intensity Chemotherapy(CT)Treatment for Older Adults With Newly Diagnosed Philadelphia(Ph)-Negative B-Cell Precursor Acute Lymphoblastic Leukemia(BCP-ALL)is Well Tolerated and Efficacious:Safety Run-In Results for the Phase 3 Randomized Controlled Golden Gate Study Amgen/Astellas/BeiGene blinatum
56、omab CD3 x CD19 BsAb Ph 2 PH-ve ALL CMR 80%;Blina-CELL 29 NCT04554485 Single Cycle of Blinatumomab Followed By High-Dose Chemotherapy in the Induction Therapy for Ph-Negative Acute Lymphoblastic Leukemia in Adults.Primary Endpoint Analysis of the Blina-Cell Trial BMS azacitidine DNMT SMD Ph 2 1L ALL
57、 3-year EFS:34.2%AALL15P1 56 NCT02828358 A Pilot Study of Azacitidine As Epigenetic Priming for Chemotherapy in Infants Less Than 1 Year of Age with KMT2A-Rearranged Acute Lymphoblastic Leukemia(ALL);Results from the Childrens Oncology Group(COG)Trial AALL15P1 Novartis ruxolitinib JAK1/2 SMD Ph 2 AL
58、L MRD-negative:44.4%AALL1521/INCB18424-269 23 NCT02723994 A Phase 2 Study of Ruxolitinib with Chemotherapy in Children with Philadelphia Chromosome-like Acute Lymphoblastic Leukemia(AALL1521/INCB18424-269):Biologic Characteristics and Minimal Residual Disease Response of Patients with Non-CRLF2-Rear
59、ranged JAK Pathway Alterations 2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 8 公司公司 通用名通用名 靶点靶点 分子类型分子类型 临床阶段临床阶段 适应症适应症 ORR(%)CR(%)mPFS,mOS(mos)实验名称实验名称 入组人数入组人数 NCT ID 摘要题目摘要题目 Pfizer inotuzumab ozogamicin CD22 ADC Ph 2 ALL MRD negativity:35%ALL2418 39 NCT03610438 Gimema ALL2418:Interim Analysis of a Phase
60、IIa Study of Feasibility and Effectiveness of Inotuzumab Ozogamicin in Adult Patients with B-Cell Acute Lymphoblastic Leukemia with Positive Minimal Residual Disease before Any Hematopoietic Stem Cell Transplantation Pfizer inotuzumab ozogamicin CD22 ADC Ph 2 ALL MRD-67%27 NCT03441061 A Phase II Stu
61、dy of Inotuzumab Ozogamicin for the Treatment of Measurable Residual Disease-Positive B-Cell Acute Lymphoblastic Leukemia Pfizer inotuzumab ozogamicin CD22 ADC Ph 2 1L ALL CR/CRi:100%1-year EFS:88%INITIAL-1 45 NCT03460522 Inotuzumab Ozogamicin Induction Followed By Standard Chemotherapy Yields High
62、Remission Rates and Promising Survival in Older(55 Years)Patients with De Novo B-Lymphoblastic Leukemia(GMALL-Initial1 Trial)Juventas,CASI inaticabtagene autoleucel CD19 CAR-T Ph 2 R/R ALL CR/CRi:65.6%HY001201 53 NCT04684147 Sustained Remission and Decreased Severity of CAR T-Cell Related Adverse Ev
63、ents:A Pivotal Study Report of CNCT19(inaticabtagene autoleucel)Treatment in Adult Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia(R/R B-Cell ALL)in China Beijing Boren Hospital donor-derived CAR T CD19 CAR-T Ph 2 ALL ORR:90%BR-IIT-LCYJ-2020-005 20 NCT04689659 Efficacy and Safe
64、ty of Donor-Derived CD7 CAR T Cells for r/r T-Cell Acute Lymphoblastic Leukemia/Lymphoma:Interim Analysis from a Phase 2 Trial Sainofi,Merck clofarabine;mitoxantrone DNA,TOP II SMD,RNAi Ph 2 R/R ALL,AML MRD negative CR:88%39 NCT01842672 Final Results of Phase I/II Trial of Mitoxantrone in Combinatio
65、n with Clofarabine(MITCL)in Children with Relapsed/Refractory Acute Leukemia Roche,Abbvie venetoclax BCL-2 SMD Ph 2 ALL,AML CR/CRi(AML):28.6%;CR/CRi(ph-B-cell ALL):55.6%SZRRAL01 30 NCT05190549 Venetoclax,Cladribine Plus Low-Dose Cytarabine Achieved High Remission in Patients with Relapse/Refractory
66、Acute Leukemia:Preliminary Results of a Phase II Study Astellas blinatumomab;ponatinib CD3 x CD19,BCr-Abl BsAb,SMD Ph 2 R/R ALL,CML CMR:69%16 A Phase II Study of the Sequential Combination of Low-Intensity Chemotherapy(mini-hyper-CVD)and Ponatinib Followed By Blinatumomab and Ponatinib in Patients w
67、ith Philadelphia Chromosome-Positive(Ph+)Acute Lymphoblastic Leukemia(ALL)Roche,Abbvie venetoclax BCL-2 SMD Ph 2 AML CR/CRi:77%22 ACTRN134 A Prospective Phase 2 Study of Venetoclax and Low Dose Ara-C(VALDAC)to Target Rising Molecular Measurable Residual Disease and Early Relapse in Acute
68、Myeloid Leukemia Roche,Abbvie venetoclax BCL-2 SMD Ph 2 AML MRD response:68%25 ACTRN134 A Prospective Phase 2 Study of Venetoclax and Low Dose Ara-C(VALDAC)to Target Rising Molecular Measurable Residual Disease and Early Relapse in Acute Myeloid Leukemia DCprime DCP-001 n.a vaccine Ph 2 M
69、aintenance AML MRD response:35%ADVANCE-II 20 NCT03697707 Use of an Allogeneic Leukemia-Derived Dendritic Cell Vaccine in MRD+AML-Patients Results in MRD Conversion,Improved Relapse-Free Survival and Vaccine Induced Immune Responses to Tumor Antigens 2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 9 公司公司 通用名通用名
70、靶点靶点 分子类型分子类型 临床阶段临床阶段 适应症适应症 ORR(%)CR(%)mPFS,mOS(mos)实验名称实验名称 入组人数入组人数 NCT ID 摘要题目摘要题目 Roche,Abbvie venetoclax BCL-2 SMD Ph 2 R/R AML ORR:60%CRc:53%33 Updated Phase IIb Results of Venetoclax with FLAG-IDA in Relapsed or Refractory Acute Myeloid Leukemia Ocular therapeutix dexamethasone Glucocortico
71、id Corticoid Ph 2 1L AML CR/CRi:83.3%DEXAML-02 120 NCT03609060 Dexaml-02:A Phase II Study of Dexamethasone Added to Induction and Postremission Therapy in Older Patients with Newly Diagnosed AML.a French Innovative Leukemia Organization(FILO)Study Pfizer cytarabine DNA SMD Ph 2/3 1L AML 3-year EFS:6
72、1.2%vs 64.3%(p=0.551)JPLSG-AML-12 359 jRCTs041180128 Evaluation of High-Dose Cytarabine Induction Therapy and Flow Cytometric Measurable Residual Disease Monitoring for Children with De Novo Acute Myeloid Leukemia:A Report from the JPLSG-AML-12 Trial BMS azacitidine DNMT SMD Ph 2 1L AML ZDYYGZ201912
73、 20 NCT04248595 Azacitidine Combined with Homoharringtonine,Idarubicin/Daunorubicin,Cytarabine for Previously Untreated Patients with Acute Myeloid Leukemia:A Single-Center,Phase 2 Study n.a azacitidine;tamibarotene;venetoclax DNMT,BCL-2 SMD,SMD Ph 2 1L AML CR/CRi:100%SELECT-AML-1 6 NCT04905407 Init
74、ial Results from SELECT-AML-1,a Phase 2 Study of Tamibarotene in Combination with Venetoclax and Azacitidine in RARA-Positive Newly Diagnosed AML Patients Ineligible for Standard Induction Chemotherapy Novo Nordisk olutasidenib IDH1 SMD Ph 2 R/R AML ORR:48%CR/CRh/CRi:45%;FT2102-HEM-101 153 NCT027195
75、74 Olutasidenib(FT-2102)Induces Durable Complete Remissions in Patients with Relapsed/Refractory mIDH1 Acute Myeloid Leukemia.Results from a Planned Interim Analysis of a Phase 2 Pivotal Clinical Trial BMS nivolumab PD-1 mAb Ph 2 Maintenance AML mPFS:13.2 vs 10.9 months REMAIN 79 NCT02275533 Randomi
76、zed Phase II Study to Assess the Role of Nivolumab As Single Agent to Eliminate Minimal Residual Disease and Maintain Remission in Acute Myelogenous Leukemia(AML)Patients after Chemotherapy(NCI9706 protocol;REMAIN Trial)Gilead entospletinib Syk SMD Ph 2 1L AML CR/CRh/CRi:78%BAML-16-001 30 NCT0301399
77、8 Entospletinib(ENTO)in Combination with Cytarabine(Ara-C)and Daunorubicin(DNR)in Newly Diagnosed(ND)Adult Patients with NPM1-Mutated and FLT3-ITD Wild-Type Acute Myeloid Leukemia(AML)Is Associated with Good Response and Survival:A Phase 2 Sub-Study of the Beat AML Master Trial Kura Oncology ziftome
78、nib MLL SMD Ph 1/2 R/R AML ORR:41.7%CRc:33.3%n.a n.a 30 n.a Update on a Phase 1/2 First-in-Human Study of the Menin-KMT2A(MLL)Inhibitor Ziftomenib(KO-539)in Patients with Relapsed or Refractory Acute Myeloid Leukemia Syndax SNDX-5613 MLL SMD Ph 1 R/R AML ORR 53%CR 38%n.a AUGMENY-101 68 NCT04065399 O
79、utcomes after Transplant in Relapsed/Refractory KMT2Ar(MLLr)and mNPM1(NPM1c)leukemia Patients Achieving Remissions after Menin Inhibition:SNDX-5613(revumenib)Ph1 Experience Aptose Biosciene HM43239 FLT3/SYK SMD Ph 1/2 n.a 16%ORR,7/50 CRs n.a n.a n.a A Phase 1/2 Dose Escalation Study of the Myeloid K
80、inase Inhibitor HM43239 in Patients with Relapsed or Refractory Acute Myeloid Leukemia Curis n.a Irak-4 SMD Ph 1/2 n.a n.a n.a n.a n.a n.a Molecular Characterization of Clinical Response in Relapsed/Refractory Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome Patients Treated with Single
81、 Agent Emavusertib 2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 10 公司公司 通用名通用名 靶点靶点 分子类型分子类型 临床阶段临床阶段 适应症适应症 ORR(%)CR(%)mPFS,mOS(mos)实验名称实验名称 入组人数入组人数 NCT ID 摘要题目摘要题目 GSK,Novartis eltrombopag TPO SMD Ph 2 AML,CIT platelet transfusions:9.76 vs 12.56 EPAG 2015 110 NCT03603795 Epag 2015:A Phase II Randomized Pl
82、acebo-Controlled Study to Assess the Impact on Outcome of Eltrombopag Administered to Elderly Patients with Acute Myeloid Leukemia Receiving Induction Chemotherapy.a French Innovative Leukemia Organization(FILO)Study Roche,Abbvie ponatinib;venetoclax Bcr-Abl T3151,BCL-2 BTK,BCL-2 Ph 2 R/R AML,CML OR
83、R:75%CR/CRi:33%12 NCT04188405 A Phase II Study of the Combination of Decitabine,Venetoclax and Ponatinib in Patients with Chronic Myeloid Leukemia(CML)in Myeloid Blast Phase(MBP)or Philadelphia-Chromosome Positive(Ph+)Acute Myeloid Leukemia(AML)Celgene,BMS CC-486(oral azacitidine)protease SMD Ph 2 A
84、ML,CMML,MDS 2018-01-AZA 40 NCT03493646 In Vivo Drug Incorporation and Intracellular Dynamics of Injectable Versus Oral Azacytidine:A Phase II Open Label Multicentre Trial BMS azacitidine DNMT SMD Ph 2 AML,HSCT,MDS,MPD 4-year OS:36%39 NCT02497404 Epigenetic Priming with 5-Azacytidine Prior to Allogen
85、eic Stem Cell Transplantation for Myeloid Malignancies with In Vivo T Cell Depletion:Results of a Phase II Trial Pfizer,UCB gemtuzumab ozogamicin CD33 ADC Ph 2/3 AML,MDS CR/CRi:67.3%NCRI AML18 844 NCT02272478 A Randomized Comparison of the Fractionated Versus Single Dose Schedule of Gemtuzumab Ozoga
86、micin at Induction with Determinants of Benefit for Older AML Patients:UK NCRI AML18 Trial Results Immuneel therapeutics varnimcabtagene autoleucel CD19 CAR-T Ph 2 R/R B-cell malignancies ORR:100%IMAGINE 8 CTRI/2022/03/041162 Response,Peak and Persistence of Varnimcabtagene Autoleucel(IMN-003A),Firs
87、t-in-India Industry CD19-Directed CAR-T Cell Therapy,with Fractionated Infusions for Patients with Relapsed and/or Refractory B Cell Malignancies:Early Results(IMAGINE Study)Baylor ADI-001 CD20 CAR-T Ph 1 R/R lymphomas ORR:78%n.a n.a 11 n.a A Phase 1 Study of ADI-001:Anti-CD20 CAR-Engineered Allogen
88、eic Gamma Delta1()T Cells in Adults with B-Cell Malignancies Astrazeneca acalabrutinib BTK SMD Ph 2 1L CLL ORR:100%CR:52%31 NCT03580928 Updated Results from a Multicenter,Phase 2 Study of Acalabrutinib,Venetoclax,Obinutuzumab(AVO)in a Population of Previously Untreated Patients with CLL Enriched for
89、 High-Risk Disease Roche,Abbvie ibrutinib;venetoclax BTK,BCL-2 SMD,SMD Ph 2 1L CLL MRD 0.01%:63.8%vs 61.3%Filo 120 Preliminary Results of the Filo Phase 2 Trial for Untreated Fit Patients with Intermediate Risk Chronic Lymphocytic Leukemia Comparing Ibrutinib Plus Venetoclax(IV)Versus FCR:Results of
90、 the Month 15 MRD Evaluation n.a ibrutinib;obinutuzumab;venetoclax BTK,CD20,BCL-2 SMD,SMD Ph 2 1L CLL CR:58.5%CLL2-GIVe 41 NCT02758665 Final Analysis of the Prospective Multicenter CLL2-Give Trial of Obinutuzumab(GA101,G),Ibrutinib(I),and Venetoclax(Ve)in Untreated Patients with CLL with 17p Deletio
91、n/TP53 Mutation Johnson&Johnson daratumumab CD38 mAb Ph 2 R/R CLL ORR:78%IDA53 29 NCT03734198 Combined Treatment with Ibrutinib and Anti-CD38 Monoclonal Antibody Daratumumab in Relapsed/Refractory Chronic Lymphocytic Leukemia with TP53 Aberrations:Results of the Filo Phase II Study IDA53 Merck nemta
92、brutinib BTK C481S SMD Ph 2 3L CLL,SLL ORR:56%BELLWAVE-001 57 NCT03162536 Efficacy and Safety of Nemtabrutinib,a Wild-Type and C481S-Mutated Bruton Tyrosine Kinase Inhibitor for B-Cell Malignancies:Updated Analysis of the Open-Label Phase 1/2 Dose-Expansion Bellwave-001 Study 2022 年 12 月 9 日(星期五)彭博终
93、端报告下载:NH CMS 11 公司公司 通用名通用名 靶点靶点 分子类型分子类型 临床阶段临床阶段 适应症适应症 ORR(%)CR(%)mPFS,mOS(mos)实验名称实验名称 入组人数入组人数 NCT ID 摘要题目摘要题目 n.a ibrutinib;venetoclax BTK,BCL-2 SMD,SMD Ph 2 1L CLL,SLL ORR:100%HOVON 158/Next STEP 30 NCT04639362 Exploratory Results of PET-CT and Residual Lymph Node Fine Needle Aspiration of Pa
94、tients Treated with First-Line Venetoclax and Ibrutinib for CLL/Sll;First Interim Analysis of the Phase 2 HOVON 158/Next STEP Trial Norvatis asciminib STAMP SMD Ph 2 Add-On CML deep molecular response:28.6%vs 0%vs 4.8%ASC4MORE 84 NCT03578367 Efficacy and Safety Results from ASC4MORE,a Randomized Stu
95、dy of Asciminib(ASC)Add-on to Imatinib(IMA),Continued IMA,or Switch to Nilotinib(NIL)in Patients(Pts)with Chronic-Phase Chronic Myeloid Leukemia(CML-CP)Not Achieving Deep Molecular Responses(DMRs)with 1 Year of IMA cobimetinib Ph 2 CMML ORR:50%Concerto 6 NCT04409639 Concerto(NCT04409639):A Phase 2 T
96、rial of Cobimetinib in Newly Diagnosed and HMA-Treated CMML Patients with RAS Pathway Mutations Novartis ruxolitinib JAK1/2 SMD Ph 2 CMML ORR:17%MCC-19727 29 NCT03722407 Efficacy and Safety of Ruxolitinib for Treatment of Symptomatic Chronic Myelomonocytic Leukemia(CMML):Results of a Multicenter Pha
97、se II Clinical Trial 资料来源:招商证券(香港),ASH 2022,灰色标注,重点关注研究 2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 12 淋巴瘤淋巴瘤 研究研究进展进展 淋巴瘤前沿研究进展淋巴瘤前沿研究进展:除了来自 BTKi 丰富的数据读出,我们注意到 Affimed 的 FIC 细胞结合抗体(CD30 x CD16 BsAb)选择性的连接 NK 细胞(自然杀伤细胞)上的CD16+,以及肿瘤细胞上的 CD30+,以达到裂解肿瘤细胞的作用,在 Ph1/2 试验(NCT04074746,n=30)中读出高有效性,ORR 为 97%,CR 为 6
98、3%。图4:ASH 2022重磅研究数据读出 淋巴瘤 公司公司 通用名通用名 靶点靶点 分子类型分子类型 临床阶段临床阶段 适应症适应症 ORR(%),CR(%)实验名称实验名称 入组人数入组人数 NCT ID 摘要题目摘要题目 Merck nemtabrutinib BTK C481S SMD Ph 2 3L CLL,SLL ORR:56%BELLWAVE-001 57 NCT03162536 Efficacy and Safety of Nemtabrutinib,a Wild-Type and C481S-Mutated Bruton Tyrosine Kinase Inhibitor
99、for B-Cell Malignancies:Updated Analysis of the Open-Label Phase 1/2 Dose-Expansion Bellwave-001 Study AbbVie ibrutinib;venetoclax BTK,BCL-2 SMD,SMD Ph 2 1L CLL,SLL ORR:100%HOVON 158/Next STEP 30 NCT04639362 Exploratory Results of PET-CT and Residual Lymph Node Fine Needle Aspiration of Patients Tre
100、ated with First-Line Venetoclax and Ibrutinib for CLL/Sll;First Interim Analysis of the Phase 2 HOVON 158/Next STEP Trial Beigene zanubrutinib BTK SMD Ph 2 1L DLBCL ORR:94%17 Efficacy and Safety of Zanubrutinib Combined with R-CHOP Regimen in the Treatment of Newly Diagnosed Diffuse Large B-Cell Lym
101、phoma with Extranodal Involvement:A Single-Arm,Prospective Phase II Trial Beigene zanubrutinib BTK SMD Ph 2 1L DLBCL ORR:93%46 Zanubrutinib PLUS RCHOP(ZR-CHOP)Regimen Achieves High Complete Response Rate in the Treatment of Newly-Diagnosed Double-Expression Diffuse Large B Cell Lymphoma Beigene zanu
102、brutinib BTK SMD Ph 2 1L DLBCL CR:83.3%HNSZLYYNHL05 14 NCT04668365 Preliminary Results of a Phase Study of Zanubrutinib Combined with Immunochemotherapy in Patients with CD79A/CD79B-Mutant Diffuse Large B-Cell Lymphoma AstraZeneca acalabrutinib BTK SMD Ph 2 2L DLBCL ORR:74%;CR:53%ESR-LY-808-SCI 19 N
103、CT03736616 Initial Efficacy and Safety of Acalabrutinib Plus RICE in Transplant Eligible Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Regeneron odronextamab CD3 x CD20 BsAb Ph 2 3L DLBCL ORR:53%ELM-2 121 NCT03888105 Odronextamab in Patients with Relapsed/Refractory(R/R)Diffuse Lar
104、ge B-Cell Lymphoma(DLBCL):Results from a Prespecified Analysis of the Pivotal Phase II Study ELM-2 BMS lenalidomide multi molecular glue Ph 2 1L DLBCL ORR:95%DE-LYM2019 67 NCT04164368 Preliminary Result of Lenalidomide Combined with R-CHOP(R2-CHOP)in Newly Diagnosed Double-Expressor Diffuse Large B-
105、Cell Lymphoma:A Prospective Phase II Clinical Trial Roche,Seagen polatuzumab vedotin CD79b mAb Ph 2 2L DLBCL ORR:92%41 NCT04665765 Polatuzumab Vedotin Combined with R-ICE(PolaR-ICE)As Second-Line Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma BMS,Novartis,Beigene orelabrutinib;tisleliz
106、umab BTK,PD-1 SMD,mAb Ph 2 R/R DLBCL ORR:87.5%CR:25.0%0 ChiCTR2200056256 Efficacy and Safety of Lenalidomide,Anti-PD-1 Antibody Combined with Orelabrutinib or Rituximab in the Treatment of Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Junshi toripalimab PD-1 mAb Ph 2 1L DLBCL ORR:1
107、00%CR:87.5%TREND 37 NCT04058470 Combination Anti-PD1 Antibody and Rituximab Followed By R-CHOP for Elderly Patients with Newly Diagnosed DLBCL:Analysis of the Phase II TREND Trial 2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 13 公司公司 通用名通用名 靶点靶点 分子类型分子类型 临床阶段临床阶段 适应症适应症 ORR(%),CR(%)实验名称实验名称 入组人数入组人数 NCT ID 摘要
108、题目摘要题目 Regeneron Odronextamab CD20CD3 BsAb Ph 2 r/r DLBCL ORR:53%CR:37%ELM-2 121 NCT03888105 Odronextamab in Patients with Relapsed/Refractory(R/R)Diffuse Large B-Cell Lymphoma(DLBCL):Results from a Prespecified Analysis of the Pivotal Phase II Study ELM-2 Norvatis Rapcabtagene Autoleucel CD19 CAR-T
109、 Ph 1 r/r DLBCL n.a CR:65%n.a 45 NCT03960840 YTB323(Rapcabtagene Autoleucel)Demonstrates Durable Efficacy and a Manageable Safety Profile in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma:Phase I Study Update Crisper therapeutics CTX110 CD19 CAR-T Ph1 r/r LBCL ORR:67%CR:41%CARBON 34
110、 NCT04035434 CTX110 Allogeneic CRISPR-Cas9Engineered CAR T Cells in Patients(Pts)with Relapsed or Refractory(R/R)Large B-Cell Lymphoma(LBCL):Results from the Phase 1 Dose Escalation Carbon Study Astellas,Eisai bendamustine DNA SMD Ph 2 DLBCL,FL,MCL primary endpoint:19.5%vs 20.9%108 NCT02278796 A Ran
111、domized Phase II Trial Comparing BeEAM with BEAM As Conditioning Regimen for Autologous Stem Cell Transplantation in Lymphoma Patients Regeneron,Zai Lab odronextamab CD3 x CD20 BsAb Ph 2 3L FL ORR:81%ELM-2 96 NCT03888105 Odronextamab in Patients with Relapsed/Refractory(R/R)Follicular Lymphoma(FL)Gr
112、ade 13a:Results from a Prespecified Analysis of the Pivotal Phase II Study ELM-2 Baylor,UNC,Tessa TT11 CD30 CAR-T Ph 2 R/R HL ORR:73.3%CHARIOT 15 NCT04268706 Updated Results and Correlative Analysis:Autologous CD30.CAR-T-Cell Therapy in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma
113、(CHARIOT Trial)Seagen brentuximab vedotin;nivolumab CD30,PD-1 ADC Ph 2 HL ORR:93%CR:88%SGN35-027 58 NCT03646123 Brentuximab Vedotin,Nivolumab,Doxorubicin,and Dacarbazine(AN+AD)for Advanced Stage Classic Hodgkin Lymphoma:Updated Efficacy and Safety Results from the Single-Arm Phase 2 Study(SGN35-027
114、Part B)CrystalGenomics camrelizumab PD-1 mAb Ph 2 1L HL ORR:100%CR:88.2%;20 Phase II Clinical Trial of Camrelizumab Combined with AVD(Epirubicin,Vincristine and Dacarbazine)in the First-Line Treatment for Patients with Advanced Classical Hodgkins Lymphoma Affimed AFM13 CD30 BsAb-NK cells Ph 1/2 R/R
115、lymphomas ORR:97%CR:63%n.a 30 NCT04074746 Innate Cell Engager AFM13 Combined with Preactivated and Expanded Cord Blood-Derived NK Cells for Patients with Double Refractory CD30+Lymphoma Fosun kite,Daichi Sankyo axicabtagene ciloleucel CD19 CAR-T Ph 2 2L LBCL ALYCANTE 43 NCT04531046 Axicabtagene Cilo
116、leucel As Second-Line Therapy for Large B-Cell Lymphoma in Transplant-Ineligible Patients:Primary Analysis of Alycante,a Phase 2 Lysa Study CRISPR Therapeutics CTX110 CD19 CAR-T Ph1 n.a ORR:67%CR:41%n.a n.a n.a CTX110 Allogeneic CRISPR-Cas9Engineered CAR T Cells in Patients(Pts)with Relapsed or Refr
117、actory(R/R)Large B-Cell Lymphoma(LBCL):Results from the Phase 1 Dose Escalation Carbon Study Autolus AUTO4 TRBC1 CAR-T Ph 1 n.a ORR:9/73 CR:5/73 n.a 73 NCT03590574 First in Human Study of AUTO4,a TRBC1-Targeting CAR T-Cell Therapy in Relapsed/Refractory TRBC1-Positive Peripheral T-Cell Lymphoma Pfiz
118、er doxycycline 30S subunit SMD Ph 2 1L MALT lymphoma ORR:64%IELSG39 44 NCT01820910 Six-Month Doxycycline Is Safe and Effective As Upfront Monotherapy for Stage-I Malt Lymphoma of the Ocular Adnexae:Primary Endpoint Results of the IELSG39 Trial 2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 14 公司公司 通用名通用名 靶点靶点
119、分子类型分子类型 临床阶段临床阶段 适应症适应症 ORR(%),CR(%)实验名称实验名称 入组人数入组人数 NCT ID 摘要题目摘要题目 Roche CD19 4-1BBL CD19 BsAb Ph 1 ORR:67%CR:73%n.a 70 NCT04077723 CD19 4-1BBL(RO7227166)a Novel Costimulatory Bispecific Antibody Can be Safely Combined with the T-Cell-Engaging Bispecific Antibody Glofitamab in Relapsed or Refrac
120、tory B-Cell Non-Hodgkin Lymphoma Xencor Plamotamab CD20CD3 BsAb Ph 1 ORR:47.4%CR:30.8%n.a 36 NCT02924402 A Phase 1 Study of Plamotamab,an Anti-CD20 x Anti-CD3 Bispecific Antibody,in Patients with Relapsed/Refractory Non-Hodgkins Lymphoma:Recommended Dose Safety/Efficacy Update and Escalation Exposur
121、e-Response Analysis Merck pembrolizumab PD-1 mAb Ph 2 3L NKTCL,LBCL,PMBCL ORR:28%CR:23%17 NCT03210662 Phase II Study of Pembrolizumab and Fractionated External Beam Radiotherapy in Patients with Relapsed and Refractory Large B-Cell Lymphoma Beigene zanubrutinib BTK SMD Ph 2 1L WM ORR:100%;BDH-WM2020
122、/04 20 NCT04463953 Zanubrutinib Plus Ixazomib and Dexamethasone for Newly Diagnosed Symptomatic Waldenstrm Macroglobulinemia:A Prospective,Phase II Study Merck pembrolizumab PD-1 mAb Ph 2 R/R WM ORR:47.1%Pembrowm 17 NCT03630042 Pembrowm:Results of a Multi-Centre Phase II Trial Investigating the Safe
123、ty and Efficacy of Rituximab and Pembrolizumab in Relapsed/Refractory Waldenstrms Macroglobulinaemia 资料来源:招商证券(香港),ASH 2022,灰色标注,重点关注研究 2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 15 创新治疗技术创新治疗技术 CAR-T治疗治疗研究进展研究进展 CAR-T治疗前沿研究进展治疗前沿研究进展:1)丰富数据)丰富数据显示显示显示突出显示突出有效性有效性:我们注意到CAR-T治疗在r/r HC肿瘤领域读出突出的有效性数据。其中,Johns
124、on/Legend Bio的BCMA CAR-T ciltacabtagene autoleucel在CARTIFAN-1 试验中用于治疗r/r MM(ORR=100%)有效性数据突出。此外,CARTIFAN-1数据读出显示了在晚期 MM患者中的取得良好疗效风险获益。晚期(4L)MM患者在26.4 mos的中位随访期,ORR读出为85.4%,CR为79.2%。24个月的PFS和OS分别为52.6%和74.2%。2)新型)新型CAR-T编辑技术显示治疗编辑技术显示治疗获益:获益:新型细胞工程技术展示了克服当前CAR-T治疗安全性和生产方面的局限。其中,我们注意到Adicet的ADI-001(CD
125、20 CAR-T)用于治疗B细胞恶性肿瘤显示出良好的有效性(ORR读出为78%,CR为78%),未显示有G3 GvHD风险,并且没有G3 GRS 或NT报道。除此之外,CRISPR therapeutics展示了运用CRISPR/Cas9编辑系统制备异体(allo)CAR-T的能力(ORR为67%,CR为41%),没有G3 CRS,且仅有2/32例G3 NT报道。图5:ASH 2022研究数据读出 CAR-T治疗 公司公司 通用名通用名 靶点靶点 分子类型分子类型 适应症适应症 临床阶段临床阶段 ORR(%)CR(%)mPFS/mOS(mos)/其他其他 试验名称试验名称 入组人数入组人数 N
126、CT ID 摘要题目摘要题目 Immuneel therapeutics varnimcabtagene autoleucel CD19 CAR-T R/R B-cell malignancies Ph 2 ORR:100%IMAGINE 8 CTRI/2022/03/041162 Response,Peak and Persistence of Varnimcabtagene Autoleucel(IMN-003A),First-in-India Industry CD19-Directed CAR-T Cell Therapy,with Fractionated Infusions for
127、 Patients with Relapsed and/or Refractory B Cell Malignancies:Early Results(IMAGINE Study)JOHSON,Legend ciltacabtagene autoleucel BCMA CAR-T R/R MM ORR 85.4%CR 75%PFS:NR,24 mos:52.6%CARTIFAN-1 48 Phase 2,Open-Label Study of Ciltacabtagene Autoleucel,an Anti-BCMA CAR-T Cell Therapy,in Chinese Patient
128、s with Relapsed/Refractory Multiple Myeloma(CARTIFAN-1):26-Month Median Follow-up JOHSON,Legend ciltacabtagene autoleucel BCMA CAR-T R/R MM ORR 100%CR 90%CARTITUDE-2 19 Ciltacabtagene Autoleucel(Cilta-cel),a BCMA-Directed CAR-T Cell Therapy,in Patients with Multiple Myeloma(MM)and Early Relapse afte
129、r Initial Therapy:CARTITUDE-2 Cohort B 18-Month Follow-up Fosun kite,Daichi Sankyo axicabtagene ciloleucel CD19 CAR-T 2L LBCL Ph 2 CMR:67.5%ALYCANTE 43 NCT04531046 Axicabtagene Ciloleucel As Second-Line Therapy for Large B-Cell Lymphoma in Transplant-Ineligible Patients:Primary Analysis of Alycante,
130、a Phase 2 Lysa Study JW theraputics relmacabtagene autoleucel CD19 CAR-T 3L R/R MCL Ph 2 ORR:72.7%CR:54.5%JWCAR029-005 35 NCT04718883 Preliminary Safety and Efficacy of Relmacabtagene Autoleucel(relma-cel)in Adults with Relapsed/Refractory Mantle Cell Lymphoma(r/r MCL)in China Baylor,UNC,Tessa TT11
131、CD30 CAR-T R/R HL Ph 2 ORR:73.3%CHARIOT 15 NCT04268706 Updated Results and Correlative Analysis:Autologous CD30.CAR-T-Cell Therapy in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma(CHARIOT Trial)Juventas,CASI inaticabtagene autoleucel CD19 CAR-T R/R B-cell ALL Ph 2 CR/CRi:65.6%HY001
132、201 53 NCT04684147 Sustained Remission and Decreased Severity of CAR T-Cell Related Adverse Events:A Pivotal Study Report of CNCT19(inaticabtagene autoleucel)Treatment in Adult Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia(R/R B-Cell ALL)in China CARsgen zevorcabtagene autole
133、ucel BCMA CAR-T R/R MM Ph 2 ORR:92.8%CR/sCR:42.2%LUMMICAR STUDY 1 102 NCT03975907 Phase Study of Fully Human BCMA-Targeting CAR-T Cells(Zevorcabtagene Autoleucel)in Patients with Relapsed/Refractory Multiple Myeloma 2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 16 公司公司 通用名通用名 靶点靶点 分子类型分子类型 适应症适应症 临床阶段临床阶段 ORR
134、(%)CR(%)mPFS/mOS(mos)/其他其他 试验名称试验名称 入组人数入组人数 NCT ID 摘要题目摘要题目 Beijing Boren Hospital donor-derived CAR T CD19 CAR-T T-cell ALL Ph 2 ORR:90%BR-IIT-LCYJ-2020-005 20 NCT04689659 Efficacy and Safety of Donor-Derived CD7 CAR T Cells for r/r T-Cell Acute Lymphoblastic Leukemia/Lymphoma:Interim Analysis fro
135、m a Phase 2 Trial Adicet CAR-T CD20 CAR-T B cell malignancies Ph 1 ORR:78%CR:78%n.a 11 n.a A Phase 1 Study of ADI-001:Anti-CD20 CAR-Engineered Allogeneic Gamma Delta1()T Cells in Adults with B-Cell Malignancies Crisper therapeutics CTX110 CD19 CAR-T DLBCL Ph1 ORR:67%CR:41%n.a CARBON 34 NCT04035434 C
136、TX110 Allogeneic CRISPR-Cas9Engineered CAR T Cells in Patients(Pts)with Relapsed or Refractory(R/R)Large B-Cell Lymphoma(LBCL):Results from the Phase 1 Dose Escalation Carbon Study Novartis ibrutinib;tisagenlecleucel BTK,CD19 SMD,CAR-T R/R MCL Ph 2 ORR:90%CR:80%TARMAC 21 NCT04234061 Time-Limited Ibr
137、utinib and Tisagenlecleucel Is Highly Effective in the Treatment of Patients with Relapsed or Refractory Mantle Cell Lymphoma,Including Those with TP53 Mutated and Btki-Refractory Disease:First Report of the Tarmac Study BMS idecabtagene vicleucel BCMA CAR-T MM Ph 2 ORR:83.8%CR:45.9%KarMMa-2 39 NCT0
138、3601078 KarMMa-2 Cohort 2a:Efficacy and Safety of Idecabtagene Vicleucel in Clinical High-Risk Multiple Myeloma Patients with Early Relapse after Frontline Autologous Stem Cell Transplantation 资料来源:招商证券(香港),ASH 2022,灰色标注,重点关注研究 2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 17 附录附录A:FDA批准批准用于治疗血液肿瘤的药品用于治疗血液肿瘤的
139、药品 在2020年至2022年FDA批准的35种药品中,我们注意到MM(13/36)和 AML(5/36)是最受关注的适应症,CAR-T 疗法(9/35)标志着新技术研发的趋势。在 ASH 2022 上,我们注意到令人印象深刻的数据读出,这些数据读出突出了未满足的医疗需求领域具有变革性治疗潜力的新技术。附录A1:FDA批准用于治疗血液肿瘤的药品(2020 2022)批准时间批准时间 公司公司 通用名通用名 商品名商品名 靶点靶点 分子分子 适应症适应症 试验名称试验名称 NCT No.入组入组 人数人数 ORR(%)CR(%)PFS(mos)OS(mos)常见常见 AE 18 Dec 2022
140、 Karyopharm selinexor XPOVIO XPO1 SMD 2/3L r/r MM BOSTON NCT03110562 402 n.a n.a 13.9 (v.s 9.5)n.a G3 AE 10%thrombocytopenia,lymphopenia 25 Oct 2022 Janssen teclistamab-cqyv Tecvayi BCMA x CD3 BsAb 4L r/r MM MajesTEC-1 NCT03145181;NCT04557098 165 63.0 39.4 11.3 n.a CRS:88%G3 0.6%;NT:81%G3 26%11 Oct
141、2022 Seagen brentuximab vedotin Adecetris CD30 ADC 1L cHL AHOD1331 NCT02166463 600 n.a n.a 3-yr EFS:92.1%(vs 82.5%)n.a G3 AE 5%:neutropenia,anemia 26 Aug 2022 Incyte pemigatinib Pemaztte FGFR1/2/3 SMD 2L r/r FGFR1+ve MM FIGHT-203 NCT03011372 28 n.a 73.7%,CCyR 70%n.a n.a CRS:79%24 Jun 2022 BMS lisoca
142、btagene maraleucel Breyanzi,liso-cel CD19 CAR-T 2L LBCL TRANSFORM NCT03575351 184 n.a n.a.mEFS 10.1(vs.2.3)n.a CRS:45%G3 1.3%;NT:27%G3 7%27 May 2022 Norvatis tisagenlecleucel Kymriah CD20 CAR-T 3L+r/r FL ELARA NCT03568461 98 86 69 n.a n.a 20%AE CRS,infection,fatigue 25 May 2022 Agios/CStone ivosiden
143、ib Tibsovo IDH1,DNMT SMD,SMD 1L AML AGILE NCT03173248 146 n.a 47 12m EFS:37%(v.s 12%)24.0 (vs 7.9)diarrhea 25%1 Apr 2022 Fosun kite,Daiichi Sankyo axicabtagene ciloleucel Yescarta CD19 CAR-T 2L LBCL ZUMA-7 NCT03391466 359 83%(vs.50%)65%(vs.32%)mEFS 8.3(vs.2.0)n.a CRS:90%G3 9%;NT:78%G3 25%28 Feb 2022
144、 Janssen,Lengend bio ciltacabtagene autoleucel Carvykti BCMA CAR-T 4L r/r MM CARTITUDE-1 NCT03548207 97 97%67%mDOR 21.8m n.a G3 CRS 5%12 Jan 2022 Rigel Pharma olutasidenib n.a IDH1 SMD r/r AML 2102-HEM-101 NCT02719574 147 48%CR/CRh/CRi:45%;mDOR 25.9m n.a.AE:nausea 20%29 Oct 2021 Novartis asciminib S
145、cemblix STAMP SMD 2L r/r CML ASCEMBL NCT03106779 233 24 wk MMR 25%(vs.13%)n.a n.a n.a Lower discontinuation 7%(vs.25%);Infection 20%14 Sep 2021 BeiGene zanubrutinib Brukinsa BTK SMD 2L MZL MAGNOLIA,BGB-3111-AU-003 NCT03846427,NCT02343120 66 56%,80%20%,20%mDOR NR(vs.8.3%m),12m DoR 72%n.a 30%AE:neutro
146、phil,infection,platelet count 23 Apr 2021 ADC Theraputics loncastuximab tesirine-lpyl Zynlonta CD19 ADC 3L LBCL LOTIS-2 NCT03589469 145 48.3%24.1%mDoR 10.3m n.a 20%neutropenia,anemia 2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 18 批准时间批准时间 公司公司 通用名通用名 商品名商品名 靶点靶点 分子分子 适应症适应症 试验名称试验名称 NCT No.入组入组 人数人数 ORR(%)C
147、R(%)PFS(mos)OS(mos)常见常见 AE 31 Mar 2021 Sanofi isatuximab Sarclisa CD38 mAb 2L+r/r MM IKEMA NCT03275285 302 86.6%(vs.82.9%)39.7%(vs 39.7%)NR (vs.19.2m)n.a 20%AE:infection,fatigue et al 26 Mar 2021 Abcam,BMS idecabtagene vicleucel Abecma BCMA CAR-T 4L R/R MM KarMMa NCT03601078 127 72%28%mDoR 11m n.a C
148、RS 85%(G3 CRS 9%)5 Mar 2021 Kite Pharma axicabtagene ciloleucel Yescarta CD19 CAR-T 2L+r/r FL ZUMA-5 NCT03105336 146 92%76%mDoR NR(vs.14.5m)n.a G3 CRS 8%26 Feb 2021 Oncopeptides melphalan flufenamide Pepaxto DNA SMD 2L r/r MM HORIZON NCT02963493 97 23.7%n.a mDoR 4.2m n.a 20%AE:infection,fatigue et a
149、l 5 Feb 2021 BMS lisocabtagene maraleucel Breyanzi CD19 CAR-T r/r MM TRANSCEND NCT02631044 192 73%54%mDoR 16.7m n.a CRS 46%(G3 CRS 4%)5 Feb 2021 TG Therapeutics umbralisib Ukoniq PI3K SMD 2L r/r MZL UTX-TGR-205 NCT02793583 69 49%16%mDoR NR n.a 18%SAE 10 Jan 2021 Kite Pharma brexucabtagene autoleucel
150、 Tecartus,Brexu-cel CD19 CAR-T r/r ALL ZUMA-3 NCT02614066 54 n.a 65%G3 CRS:3.26%;G3 NT:35%9 Jan 2021 BeiGene zanubrutinib Brukinsa BTK SMD WM ASPEN NCT03053440 201 78%(vs.78%)n.a n.a n.a n.a 16 Oct 2020 AbbVie,Genetech venetoclax Venclexta BCL-2 SMD 1L AML VIALE-A,VIALE-C NCT02993523,NCT03069352 286
151、 n.a 37%(vs.18%)n.a 14.7m(vs.9.6m);7.2m(vs.4.1m,p=0.11)nausea 30%14 Oct 2020 Merck pembrolizumab Keytruda PD-1 mAb 2L+r/r cHL KEYNOTE-204 NCT02684292 304 66%(vs.54%)25%(vs.24%)13.2m(vs.8.3m)n.a Permanent discontinuation 14%20 Aug 2020 Jassen daratumumab Darzalex CD38 mAb 2/3L r/r MM CANDOR NCT031586
152、88 466 85%n.a 28.6m (vs 15.2m)n.a 20%AE:infection,fatigue et al 5 Aug 2020 GSK belantamab mafodotin Blenrep BCMA ADC 4L r/r MM DREAMM-2 NCT 03525678 n.a 32%n.a mDoR 11m 13.7m 20%AE:keratopathy,visual acuity 31 Jul 2020 MorphoSys/Innocare tafasitamab MONJUVI CD19 mAb 2L r/r DLBCL L-MIND NCT02399085 8
153、1 55 37 mDoR 21.7m n.a neutropenia 20%24 Jul 2020 Gilead brexucabtagene autoleucel Tecartus CD19 CAR-T r/r MCL ZUMA-2 NCT02601313 74 87%62%n.a n.a G3 CRS 18%,G3 NT 37%22 Jun 2020 Karyopharm selinexor XPOVIO XPO1 SMD 3L r/r DLBCL SADAL NCT02227251 134 29%13%n.a n.a thrombocytopenia 15%18 Jun 2020 Epi
154、zyme/HCM tazemetostat Tazverik EZH2 SMD 2L r/r FL E7438-G000-101 NCT01897571 42 69%/34%12%/4%mDoR 13m n.a 20%AE fatigue,infection,nausea 16 Jun 2020 Wyeth Pharma gemtuzumab ozogamicin MYLOTARG CD33 mAb 1L AML AAML0531 NCT00372593 1,063 n.a n.a.EFS HR 0.84 3yr OS 69.4%(vs.65.4%,p=0.39)G3 infection 5%
155、资料来源:招商证券(香港),FDA 2022 年 12 月 9 日(星期五)To access our research reports on the Bloomberg terminal,type NH CMS;Reference 1:IQVID paving path in Haematological cancers 19 附录附录B:NCCN 推荐推荐血液肿瘤血液肿瘤用药指南用药指南 附录 B1:NCCN 推荐治疗指南-非霍奇金淋巴瘤(NHL)NHL 亚型亚型 美国发病率美国发病率 (每十万人每十万人)5 年生存期年生存期 NCCN 推荐一线治疗方案推荐一线治疗方案 NCCN 推荐二线
156、治疗方案推荐二线治疗方案 新研发动态新研发动态及及 临床管线进展临床管线进展 CLL/SLL 3.9 87.5%1.CD20 mAB Rituxan/Gazyva+Chemo 2.BTK 抑制剂抑制剂 Ibrutinib,zanubrutinib,acalabrutinib Acalabrutinib+/-Gazyva 3.BCl-2抑制剂抑制剂 Venetoclax+Gazvya 1.CD20 mAb Rituxan/Gazvya/Arzarra+Chemo 2.BTK 抑制剂抑制剂 Ibrutinib/Acalabrutinib 3.PI3K 抑制剂抑制剂 Duvelisib;Idelal
157、isib+Rituxan 4.BCl-2 抑制剂抑制剂 Venetoclax+Rituxan 5.Others Lenalidomide,Ofatumumab,Alemtuzumab(CD52)+Rituxan BTK inhibitor combos(BCL-2,CD38,JAK,RO1,ATR,PI3K)PI3K+CD20 DLBCL 5.6 64.6%1.CD20 mAB Rituxan-CHOP 1.CD 19 mAb/CAR-T Yescarta/Kymriah tafasitamab 2.CD20 mAB Rituxan+Chemo 3.CD79b ADC Polatuzumab
158、vedotin-piiq CD20+CD3 bsAB CD79b+BR PI3K+CD20 CD19 CAR-T CD30 ADC(Brentuximab vedotin)BTK抑制剂(inbrutinib for non-GCB DLBCL)FL 2.6 90.2%1.CD20 mAB Rituxan/Gazvya+Chemo 1.CD20 mAB Rituxan/Gazvya+Chemo 2.PI3K 抑制剂抑制剂 Zydelig/Aliqopa CD20+CD3 bsAB PI3K+CD20 MZL-1.CD20 mAB Rituxan+Chemo 1.BTK抑制剂抑制剂 Ibrutin
159、ib PI3K+CD20 MCL-1.CD20 mAB Rituxan+Chemo 1.BTK抑制剂抑制剂 Ibrutinib/Acalabrutinib/Zanubrutinib 2.UE3 ligase Lenalidomide CD19 CAR-T WM-1.CD20 mAB+BTK Ibrutinib+Rituxan 1.BTK抑制剂抑制剂 Ibrutinib-资料来源:招商证券(香港),NCCN指南,*5年生存期 2012-2018 2022 年 12 月 9 日(星期五)To access our research reports on the Bloomberg terminal
160、,type NH CMS;Reference 1:IQVID paving path in Haematological cancers 20 附录 B2:NCCN 推荐治疗指南 血液肿瘤 肿瘤肿瘤 亚型亚型 美国发病率美国发病率 (每十万人每十万人)5 年生存年生存期期 NCCN 推荐一线治疗方案推荐一线治疗方案 NCCN 推荐二线治疗方案推荐二线治疗方案 新研发动态新研发动态及及 临床管线进展临床管线进展 ALL 1.8 70.8%1.Bcr-abl L TKi+chemo e.g ponatinib/dasatinib/bosutinib+chemo 2.TKi+corticostero
161、id 1.Tki+/-CD-19 mAb e.g Tki+Blinatumomab 2.Tki+chemo/corticosteroid 3.auto-SCT 4.CD22 ADC e.g CD22 ADC-Inotuzumab ozogamicin+/-bosutinib 5.CAR-T therapy e.g CD19 CAR-T-Tisagenlecleucel(Kymriah)6.Tki+chemo e.g.BCL-2 inhibitor Venetoclax+chemo BsAb(CD3 x cD19),JAK1/2,DNMT inhibitor,CD-19 CAR-T CLL 4.
162、1 87.9%1.BTKi e.g Zanubrutinib,Ibrutinib 2.BTKi+CD20 mAb e.g Acalabrutinib+obinutuzumab 3.BCL-2+CD20 mAb e.g Venetoclax+Obinutuzumab 4.CD20 mAb+chemo e.g rituximab+Bendamustine 5.CD20 mAb+CD52 mAb e.g rituximab+/-Alemtuzumab 1.BTKi e.g Zanubrutinib,Ibrutinib 2.BCL-2 抑制剂抑制剂+CD20 mAb e.g Venetoclax+ri
163、tuximab 3.PI3K 抑制剂抑制剂+CD20 mAb e.g ldelalisib+rituximab(e.g Duvelisib)4.CD20 mAb+chemo e.g rituximab+Bendamustine PD-1 DNMT,IDH1 inhibitor,AML 4.1 30.5%1.Chemo e.g cytarabine 2.CD33 ADC+chemo e.g gemtuzumab+chemo 3.BCL-2+LDAC e.g.venetoclax+azacitidine 4.Flt3 e.g.Gilteritinib 5.IDH1/2 e.g.Enasidenib
164、(IDH2),ivosidenib(IDH1)1.Chemo e.g cytarabine-high dose,Etoposide+cytarabine 2.CD33 ADC+chemo e.g gemtuzumab+chemo 3.auto-SCT BCL-2 inhibitor KMT2A,DNMT inhibitor,CD33 ADC CML 1.8 70.4%1,CD20 mAb+chemo e.g.Rituximab+CHOP/Bendamustine 1.BTKi e.g Zanubrutinib,Ibrutinib 2.BTKi+CD20 mAb+chemo e.g Ibruti
165、nib+rituximab+lenalidomide 3.BCL-2 抑制剂抑制剂+CD20 mAb e.g Venetoclax+rituximab 4.BCL-2 抑制剂抑制剂 +BTKi e.g Venetoclax+ibrutinib 5.allo-SCT 6.CD19 CAR-T e.g brexucabtagene autoleucel(Tecartus)CD19 CAR-T 资料来源:招商证券(香港),NCCN指南,*5年生存期 2012-2018 2022 年 12 月 9 日(星期五)To access our research reports on the Bloomber
166、g terminal,type NH CMS;Reference 1:IQVID paving path in Haematological cancers 21 附录 B3:NCCN 推荐治疗指南 多发性骨髓瘤 肿瘤肿瘤 亚型亚型 美国发病率美国发病率 (每十万人每十万人)5 年生存期年生存期 NCCN 推荐一线治疗方案推荐一线治疗方案 NCCN 推荐二线治疗方案推荐二线治疗方案 新研发动态新研发动态及及 临床管线进展临床管线进展 MM 7.1 57.9%1.三种药品联合治疗三种药品联合治疗 蛋白酶抑制剂蛋白酶抑制剂+I/O+I/O+皮质类固醇皮质类固醇)e.g.bortezomib,len
167、alidomide,dexamethsone 2.CD38 mAb e.g daratumumab 1.auto-SCT e.g Tki+Blinatumomab 2.BCMA CAR-T 治疗治疗 e.g.BCMA CAR-T 细胞,idecabtagene vicleucel,Abecma)3.BCMA ADC e.g,Blenrep BiTE(BCMA xCD3)BiTE (GPRC5D xCD3)BCMA CAR-T GPRC5D CAR-T BCMA CAR-NK BCL-2(venetoclax)XPO1(selinexor)资料来源:招商证券(香港),NCCN指南,*5年生存期
168、2012-2018 2022 年 12 月 9 日(星期五)To access our research reports on the Bloomberg terminal,type NH CMS;Reference 1:IQVID paving path in Haematological cancers 22 附录附录C:主要管线产品主要管线产品及销售预测及销售预测 附录 C1:血液肿瘤发病率及销售预测 血液肿瘤发病率以及主要血液类型的销售预测 主要血液肿瘤疾病销售预测 肿瘤肿瘤 发病率发病率(万万/年年)死亡率死亡率(万万/年年)5 5 年生存期年生存期(%)(%)非霍奇金淋巴瘤 5.8
169、 2.6 73.20%白血病 5.4 3.3 65%黑色素瘤 1.8 1.1 55.60%霍奇金淋巴瘤 0.98 0.26 88.30%肿瘤类似肿瘤类似 2021 2022 2023 2024 2025 非霍奇金淋巴瘤 13,090 13,076 13,974 15,565 17,671 白血病 1,431 1,634 2,266 3,077 4,395 黑色素瘤 23,609 23,892 25,227 26,975 28,352 霍奇金淋巴瘤 1,506 1,925 2,200 2,361 2,562 资料来源:招商证券(香港),IQVIA 2020 附录 C2:血液肿瘤领先资产及销售预测
170、 2028年销售预测(百万美元)资料来源:招商证券(香港),Evaluate Pharma;红圈为CAR-T治疗 14,5152,3592,1091,9931,8931,7041,6251,6151,4171,1741,0551,00798297796295684780780679002,0004,0006,0008,00010,00012,00014,00016,000百万美元百万美元肿瘤免疫领域关键资产肿瘤免疫领域关键资产(产品-机理-适应症-公司)Darzalex-CD38 mAb-MM-强生Carvykti-BCMA CAR-T-MM-强生Polivy-CD79B ADC-NHL-罗氏
171、Yescarta-CD19 mAb-NHL-吉利德Tecvayli-BCMA x CD3 BsAb-强生Breyanzi-CD19 CAR-T-BMS Abecma-BCMA CAR-T-BMS Sarclisa-CD38 mAb-MM-赛诺菲Gazyva-CD20 mAb-NHL-罗氏Adcetris-TNFRSF8 ADC-HL-Seagen&J 领先小分子资产领先小分子资产(产品-机理-适应症-公司)-公司)Calquenece-BTKi-NHL-阿斯利康Venclexta-BCL-2i-Leukeamia-艾伯维Imbruvica-BTKi-NHL-艾伯维Ninlaro-Beta ty
172、pe-5-MM-武田制药Brukinsa-BTKi-NHL-百济神州Xospata-FLT-3i-Leukeamia-安斯泰来Kyprolis-Beta type-5i-MM-武田制药23,60923,89225,22726,97528,352010,00020,00030,00040,00050,00060,000202242025美元美元(百万百万)非霍奇金淋巴瘤白血病黑色素瘤霍奇金淋巴瘤01234567非霍奇金淋巴瘤白血病黑色素瘤霍奇金淋巴瘤发病率(万/年)死亡率(万/年)5年生存期(%)2022 年 12 月 9 日(星期五)To access our resea
173、rch reports on the Bloomberg terminal,type NH CMS;Reference 1:IQVID paving path in Haematological cancers 23 附录C3:血液肿瘤领域主要管线产品及销售预测(百万美元)产品产品 适应症适应症 公司公司 通用名通用名 靶点靶点 分子分子 2021 2022 2023 2024 2025 2026 2027 2028 ASH 2022 摘要摘要 Darzalex MM Johnson&Johnson daratumumab CD38 mAb 6,023 7,894 9,505 10,891 1
174、2,043 13,020 13,821 14,515 Y Carvykti MM Johnson&Johnson ciltacabtagene autoleucel BCMA CAR-T n.a 75 345 878 1,347 1,761 2,121 2,359 Y Calquence NHL AstraZeneca acalabrutinib BTK SMD 663 803 1,041 1,295 1,542 1,750 1,924 2,109 Y Polivy NHL Roche polatuzumab vedotin CD79B ADC 270 468 822 1,160 1,467
175、1,652 1,833 1,993 Y Yescarta NHL Gilead Sciences axicabtagene ciloleucel CD19 CAR-T cell 695 1,135 1,273 1,415 1,521 1,644 1,789 1,893 Y Tecvayli MM Johnson&Johnson axicabtagene ciloleucel BCMA x CD3 BsAb n.a n.a n.a 373 523 804 1,180 1,704 Y Breyanzi NHL Bristol Myers Squibb lisocabtagene maraleuce
176、l CD19 CAR-T cell 87 183 429 738 988 1,244 1,435 1,625 Y Abecma MM Bristol Myers Squibb idecabtagene vicleucel BCMA CAR-T 164 360 569 808 1,050 1,300 1,463 1,615 Y Venclexta AML,CLL AbbVie venetoclax BCL-2 SMD 426 607 826 1,006 1,144 1,255 1,340 1,417 Y Imbruvica NHL AbbVie ibrutinib BTK SMD 1,060 9
177、67 1,035 1,072 1,103 1,132 1,133 1,174 Y Sarclisa MM Sanofi isatuximab CD38 mAb 208 320 477 617 773 908 989 1,055 Y Ninlaro MM Takeda ixazomib citrate beta type-5 SMD 813 824 881 935 998 1,044 1,019 1,007 N Brukinsa NHL BeiGene zanubrutinib BTK SMD 184 228 375 562 753 919 943 982 Y Xospata AML Astel
178、las Pharma gilteritinib fumarate FLT-3 SMD 304 372 451 538 656 769 873 977 N Kyprolis MM Amgen carfilzomib beta type-5 SMD 1,108 1,218 1,294 1,390 1,362 1,348 1,275 962 Y Gazyva NHL Roche obinutuzumab CD20 mAb 570 615 676 721 784 853 912 956 Adcetris HL Seagen brentuximab vedotin TNFRSF8 ADC 514 477
179、 533 592 632 694 772 847 Y FT516 NHL Fate Therapeutics n.a NK cell therapy T-Cell 23 101 268 439 608 807 N Epcoritamab NHL Genmab epcoritamab CD20 mAb 49 185 352 509 670 806 N Imbruvica NHL Johnson&Johnson ibrutinib BTK SMD 663 677 751 668 714 748 778 790 Y 资料来源:招商证券(香港),Evaluate,CMS(HK);ASH 2022,公司
180、信息;灰色,关键中国资产,ASH发表摘要:Y:有,N:无 2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 24 附录附录D:参考文献参考文献 1.Rafei,H.,Daher,M.,&Rezvani,K.(2021).Chimeric antigen receptor(CAR)natural killer(NK)cell therapy:leveraging the power of innate immunity.British journal of haematology,193(2),216-230.2.Daher,M.,Melo Garcia,L.,Li,Y.,
181、&Rezvani,K.(2021).CARNK cells:the next wave of cellular therapy for cancer.Clinical&Translational Immunology,10(4),e1274.3.Smith,E.L.,Harrington,K.,Staehr,M.,Masakayan,R.,Jones,J.,Long,T.J.,.&Brentjens,R.J.(2019).GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed C
182、AR T cells.Science translational medicine,11(485),eaau7746.4.Erba,H.P.,Fathi,A.T.,Issa,G.C.,Altman,J.K.,Montesinos,P.,Patnaik,M.M.,.&Wang,E.S.(2022).Update on a Phase 1/2 First-in-Human Study of the Menin-KMT2A(MLL)Inhibitor Ziftomenib(KO-539)in Patients with Relapsed or Refractory Acute Myeloid Leu
183、kemia.Blood,140(Supplement 1),153-156.5.Issa,G.C.,Cuglievan,B.,Stein,E.,Arellano,M.L.,ucenka,A.,Khera,N.,.&Aldoss,I.(2022).Outcomes after Transplant in Relapsed/Refractory KMT2Ar(MLLr)and mNPM1(NPM1c)leukemia Patients Achieving Remissions after Menin Inhibition:SNDX-5613(revumenib)Ph1 Experience.Blo
184、od,140(Supplement 1),914-916.2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 25 投资风险投资风险 主要风险包括:临床资产的临床失效;数据差于预期;监管延误。2022 年 12 月 9 日(星期五)彭博终端报告下载:NH CMS 26 投资评级定义 行业投资评级 定义 推荐 预期行业整体表现在未来 12 个月优于市场 中性 预期行业整体表现在未来 12 个月与市场一致 回避 预期行业整体表现在未来 12 个月逊于市场 公司投资评级 定义 增持 预期股价在未来 12 个月上升 10%以上 中性 预期股价在未来 12 个月上升或下跌 10%或以
185、内 减持 预期股价在未来 12 个月下跌 10%以上 分析师声明分析师声明 主要负责撰写本研究报告全部或部分内容的分析师在此声明:(i)本研究报告所表述的任何观点均精准地反映了上述每位分析师个人对所评论的证券和发行人的看法;(ii)该分析师所得报酬的任何组成部分无论是在过去、现在及将来均不会直接或间接地与研究报告所表述的具体建议或观点相关系。监管披露监管披露 有关重要披露事项,请参阅本公司网站之披露网页 http:/.hk/cmshk/gb/disclosure.html 或http:/.hk/Research/Disclosure。免责条款免责条款 本报告由招商证券(香港)有限公司提供。本报
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