20240612_华创证券_医药行业IO+ADC新时代系列七：RC48+IO 有望拓展尿路上皮癌早线适应症_13页.pdf

2009 1210 2024 06 12 IO+ADC RC48+IO 2014 Keytruda Opdivo PD-1 IO 20 400 IO cHL PD-1/L1 ORR 10-30%PD-1/L1 IO 5-10 IO ADC ADC IO Nectin-4 ADC Padcev la/mUC FDA TROP2 ADC CLDN18.2 ADC EGFR HER3 ADC HER2 ADC B7H3 ADC TF ADC PD-1/L1 1 IO+ADC 5-10 2 IO IO+IO+ADC 100-200%3 ADC IO+ADC 2024 ASCO MIBC IO+ADC RC48 pCR 62.1%RC48 PD-1 PD-1/CTLA-4 IO HER2 ADC+IO S0360520120002 S0360524020002%()475 0.06()60,551.31 6.98()50,039.55 7.36%1M 6M 12M-7.0%-15.6%-15.9%-3.6%-19.0%-8.1%IO+ADC PD-1+TROP2 ADC HR+2024-06-06 IO+ADC PD-1+TROP2 ADC NSCLC 2024-06-03 IO+ADC 2023-04-10-25%-15%-5%5%23/06 23/08 23/11 24/01 24/03 24/062023-06-122024-06-12 300 IO+ADC 2009 1210 2 RC48+IO.4 MIBC HER2 ADC+IO.4 K MIBC pCR 42%.5 HER2 ADC+IO pCR.6 RC48+MIBC pCR 61.3%.6 RC48+MIBC cCR 68.75%.7 RC48+MIBC pCR 50%.7 UC HER2 ADC+IO.7 PD-1/L1 UC.7 RC48+IO ORR.9 RC48-C014 RC48+ORR 76%.9 AK104-RC48 UC 01 RC48+ORR 75%.9 RC48+PD-1 III.9 HER2 ADC+IO.10 YWCXuNmRmPrQrPsRrMrOrQ6M9RaQpNrRmOqMeRnNoQlOmNtP6MoOxONZoOtMNZrNpQ IO+ADC 2009 1210 3 1 RC48+IO II III IST.4 2 PURE-01.5 3 PURE-01.5 4 RC48-C017.6 5 RC48-C017.6 6 2023 CSCO UC.8 7 RC48-C016.10 8 KEYNOTE-D74.10 9 UC pCR%.10 10 UC ORR%.10 IO+ADC 2009 1210 4 RC48+IO RC48 HER2 ADC vc auristatin E MMAE HER2 disitamab RC48 HER2 IHC 2+3+la/m UC 2 HER2 la/m G/GEJ RC48+IO 1 RC48+IO II III IST/RC48-C035 II/III 2L HER2 G/GEJ+RC48 ORR/AE OS/PFS 90 2024-02 RC48-C027 II/III 1L HER2+CAPOX+60 2023-08 RC48-C022 II HER2 cT3-4aN+G/GEJ+XELOX XELOX pCR 90 2023-11 KEYNOTE-D74 III 1L UC+/PFS/OS 700 2023-09 RC48-C016 III 1L HER2 UC+/PFS/OS 452 2022-06 KEYNOTE-D78 II 1L HER2 UC+RC48 cORR/AEs 332 2022-05 RC48-C017 II MIBC+pCR 40 2022-05 RC48-C024 II HR-/HER2 BC+tpCR 120 2023-07 RC48-C025 II HR+/HER2 T1c-T2cN1-2M0 T3cN0-2M0 BC+tpCR 79 2024-04 RC48-C026 II HER2+T2-3cN0-3M0 BC+pCR 80 2023-11 RC48-C033 II HR-/HER2 BC+RC48 PFS 80 2024-12 RC48-C030 II 2L HER2+ORR/AEs 116 2024-01 ClinicalTrials.gov MIBC HER2 ADC+IO IARC GLOBOCAN 2022 61.4 22.1 NMIBC MIBC 2022 NMIBC 75%Tis 10%Ta 70%T1 20%T2 3SNnZ2GUyFUOuX10E32+SpDzSda0ryHb0G1WUCrSdD7R2ujOaNGPnbbIozx93+vF IO+ADC 2009 1210 5 MIBC CSCO 2023 MIBC 5%8%GC+ddMV AC+ddMV AC GC MIBC III V05 VESPER pCR 42%36%P=0.2 437 3 PFS 66%56%HR=0.70 P=0.025 K MIBC pCR 42%PURE-01 NCT02736266 II MIBC RC RC cT2-3bN0M0 T N M MIBC 2017 2 2018 3 50 21 42%cT2 27 54%cT3 2 4%cT2-3N1 pCR 42%PD-L1 P=.011 35 PD-L1 CPS 10%pCR 54.3%15 PD-L1 CPS10%pCR 13.3%2 PURE-01 3 PURE-01 Andrea Necchi et al.,Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma(PURE-01):An Open-Label,Single-Arm,Phase II Study Andrea Necchi et al.,Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma(PURE-01):An Open-Label,Single-Arm,Phase II Study IO+ADC 2009 1210 6 HER2 ADC+IO pCR RC48+MIBC pCR 61.3%2024 ASCO II RC48-C017 RC48 HER2 MIBC RC48-C017 pCR MIBC cT2-T4aN0-1M0 RC+PLND+HER2 IHC 1+2mg/kg RC48+3 mg/kg 2 6 4 RC+PLND 3 mg/kg 2 20 2022 5 2024 1 47 cT2N0 40.4%cT3N0 29.8%cT4aN0 12.8%cT2-4aN1 17.0%HER2 IHC 1+2+3+10.6%57.4%31.9%45 2 78.7%6 6.4%6 14.9%6 2024 4 15 31 pCR 61.3%74.2%EFS 5.4 EFS 12 EFS 85.0%DFS OS TRAE 1 2 14.9%3-4 TRAE TRAEs 3-5 RC48 4 RC48-C017 5 RC48-C017 ASCO 2024 ASCO 2024 IO+ADC 2009 1210 7 RC48+MIBC cCR 68.75%Ib/II Hope-03 51 cT2-4bN0-3M0-1a HER2 MIBC RC48 120mg 2 200mg 3 2024 ASCO Hope-03 18 7 HER2 IHC 2+11 HER2 IHC 3+T2-4aN0-3M1a 16 7 T0 4 Tis 2 PR 2 SD 1 cCR T0/Ta/Tis 68.75%DCR 90.91%14 6 2 pT3N0M0 4 10 RC48 RC48+MIBC pCR 50%RCVDUCIIR012 NCT06074484 II RC48 PD-1/CTLA-4 HER2 IHC 1+/2+/3+MIBC T2-T4aN0-1M0 RC48 2.0 mg/kg D1 Q2W 4+6.0 mg/kg D1 Q2W 4 RC48 2.0 mg/kg D1 Q3W 6+10.0 mg/kg D1 Q3W 14 2024 1 18 84.6%HER2 IHC 2+3+50%PD-L1 CPS 10 5 2 PR 3 SD DCR 100%4 1 4 ypT1N0M0 2 2/4 50%pCR pT0N0M0 2 SD 1 14 TRAEs 35.7%2 3 TRAEs 14.3%4 3 UC HER2 ADC+IO PD-1/L1 UC UC ORR 50%ORR PD-1/L1 UC III PD-1/L1 UC IMvigor130 KEYNOTE-361 DANUBE PD-1/L1 UC IO+ADC 2009 1210 8 UC PD-1/L1 ORR OS 2023 CSCO UC PD-1/L1 UC PD-1/L1 ORR 30%RC48 HER2 la/m UC II RC48-C009 64 HER2 IHC 2+/3+UC 85.9%RC48 ORR 50.0%RC48 ORR 55.6%mPFS 5.3 mOS 14.2 HER2 UC RC48 2022 ASCO RC48-C011 RC48 HER2 IHC 0/1+UC ORR 26.3%DCR 94.7%HER2 IHC 1+ORR 38%HER2 mPFS 5.5 mOS 16.4 6 2023 CSCO UC CSCO 2023 IO+ADC UC III EV302 Nectin-4 ADC enfortumab vedotin EV+GC PFS OS mOS 31.5 vs 16.1 HR 0.47 P0.0001PFS 12.5 vs 6.3 HR 0.45 P 0.0001 ORR 67.7%vs 44.4%P0.00001 CR 29.1%vs 12.5%EV+UC IO+ADC 2009 1210 9 RC48+IO ORR RC48-C014 RC48+ORR 76%2023 ASCO Ib/II RC48-C014 RC48/UC 41 la/m UC 59%HER2 IHC 2+3+32%PD-L1 2 2mg/kg RC48+3mg/kg 2022 11 18 cORR 73.2%9.8%CR ORR 76.0%DCR 90.2%mPFS 9.2 2 OS 63.2%HER2 IHC 3+/2+IHC 1+IHC 0 ORR 83.3%64.3%33.3%PD-L1 ORR 61.5%78.6%TRAE 43.9%3 TRAE 23 56.1%AEs 14.6%3 AK104-RC48 UC 01 RC48+ORR 75%AK104-RC48 UC 01 NCT06178601 II RC48-ADC mUC 2024 2 4 13 la/mUC 85%HER2 IHC 2+3+PD-L1 100%6 DLT ALT/AST 4mg/kg Q2W RC48 8 ORR 75.0%6/8 CR 12.5%1/8 DCR 100%PFS OS 69.2%9/13 TRAE 15.4%2/13 3 TRAE 30.8%AEs 3 irAE 15.4%RC48+PD-1 III 2021 8 9 Seagen Inc Seagen Seagen 2 24 2023 3 430 Seagen RC48+HER2+la/mUC III KEYNOTE-D74 NCT05911295 2026 RC48+/III HER2 la/mUC IO+ADC 2009 1210 10 7 RC48-C016 8 KEYNOTE-D74 ClinicalTrials.gov ClinicalTrials.gov HER2 ADC+IO RC48+IO MIBC UC 9 UC pCR%10 UC ORR%CSCO 2023 2024 ASCO Meeting Abstracts The Art and Science of Cancer Care:From Comfort to Cure Christian Pfister et al.,Dose-Dense Methotrexate,Vinblastine,Doxorubicin,and Cisplatin or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients With Nonmetastatic Muscle-Invasive Bladder Cancer:Results of the GETUG-AFU V05 VESPER Trial Andrea Necchi et al.,Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma(PURE-01):An Open-Label,Single-Arm,Phase II Study CSCO 2023 Xinan Sheng et al.,Disitamab vedotin,a novel humanized anti-HER2 antibody-drug conjugate(ADC),combined with toripalimab in patients with locally advanced or metastatic urothelial carcinoma:An open-label phase 1b/2 study 2024 ASCO Meeting Abstracts The Art and Science of Cancer Care:From Comfort to Cure Thomas Powles et al.,1L pembrolizumab(pembro)versus chemotherapy(chemo)for choice-of-carboplatin patients with advanced urothelial carcinoma(UC)in KEYNOTE-361 01020304050607080ddMVACGCK 药RC48+特瑞普利（HER2+）RC48+替雷利珠（HER2+）RC48+卡度尼利（HER2+）01020304050607080GCGPK 药(全人群）K 药（PD-L1 CPS10）K 药+化疗EV+K 药RC48+特瑞普利（HER2+）RC48+卡度尼利（HER2+）IO+ADC 2009 1210 11 2020 2020 2020 2020 2020 2020 2023 2021 2022 2022 2022 2023 2023 2024 IO+ADC 2009 1210 12 010-63214682 010-63214682 010-63214682 010-63214682 010-63214682 010-66500808 010-66500821 010-63214682 0755-82828570 0755-83715428 0755-82756804 0755-82871425 021-20572536 021-20572555 021-20572257-2552 021-20572506 021-20572585 021-20572509 021-20572548 021-20572573 0755-82756805 021-20572559 021-20572559 0755-82756805 021-20572559 玙 021-25072549 IO+ADC 2009 1210 13 A 300 500/6 20%6 10%20%6-10%10%6 10%20%3-6 5%3-6-5%5%3-6 5%26 C 3A 1061 A 19 33 12 100033 518034 200120 010-66500801 0755-82027731 021-20572500 010-66500900 0755-82828562 021-20572522