20240409_中信建投_医药行业2024AACR：ADC仍是重要热点中国药物创新度提升_53页.pdf

2024AACR ADC 发布日期：2024 年4 月9 日贺菊颖SAC 执证编号：S1440517050001SFC 中央编号：ASZ591袁清慧SAC 执证编号：S1440520030001SFC 中央编号：BPW879研究助理：魏佳奥研究助理：王云鹏研究助理：赵旭 5 SKB264 MK-287024 4-1BB/CEACAM5 12024 AACR 2 ADC 3 ADC EGFR 67 III 0YEVxOqNnOqRrPsRtOsNnMbR9RbRnPoOtRsOiNpPnReRmNqQaQmMwOuOmPrRvPqRtR 12 311 TYK2 89 ADC 10 T 13 14 PROTAC 19 ADC418 15 ADC 16 ADC 17 20 fGB3KqN1FS4LDFzRY1CMQ8iCYydMK33bsDsO0TSEcfaC+UykcVN+9MJzl7KQscMh AACR5 AACR2024:ADC 2024 115 AACR 4 5 SHR4602 HER2ADC HRA00184-C004 TF-ADC IBI334(EGFR/B7H3)IBI3001 EGFR/B7H3 ADC Trop2ADC ADC ADC ADC ADC ADC PD1 TIGIT LAG-3 CTLA4 CEACAM3 EGFR B7H3 II ADC A 6 AACRA AACR Camrelizumab CT209/9 CT209/9-LA-ESCC II shr-4602 3195/12 ADC3195/12-SHR-4602 HER2 ADC Topo I HER2 ADC HRA00184-C004 3128/9 ADC 3128/9-HRA00184-C004-SDP03923-000-91063134/15 ADC3134/15-SDP03923-000-9106 LIV-1 ADC HRA00242-C004 3145/26 ADC 3145/26-HRA00242-C004 DAR PSMA ADC HRA00130-C004 3146/27 ADC 3146/27-HRA00130-C004 DLL3 ADC DAR SY-5933 1928/6 1928/6-FAK KRAS G12C SY-7021 4540/16 4540/16-SY-7021 DNA-PK Furmonertinib AST2818 1964/13 1964/13-Furmonertinib EGFR TKI EGFR PACC 20 Furmonertinib CT152/3 CT152/3-EGFR NSCLC EGFR Furmonertinib CT280/10 CT280/10-FURVENT 3 EGFR 20 NSCLC FURMO-004 olverembatinib 1971/20 1971/20-SDH APG-115 3223/7 3223/7-EED APG-5918 EEDi-5273 MDM2 alrizomadlin APG-115 PCa 9MW3811 2365/11/1 2365/11-IL-11 9MW3811 IL-11/IL-11R T PD-1 2MW4991 6349/10 6349/10-2MW4991 ADCC 2MW4691 6350/11 6350/11-2MW4691 CCR8/CTLA-4 Treg CD8+T CTLA-4 AACR 7 AACRA AACR Disitamabvedotin1901/12-ADC1901/12-Disitamab vedotin HER2-RC148 2734/25 PD-1 VEGF RC148 trop2-ADC 3136/17 ADC trop2 ADC TICTE TCE 6713/11-TICTE T Disitamab vedotin1901/12-ADC1901/12-Disitamab vedotin HER2-HP537 LB157/3 LB157/3-p300/CBP HP537 HP560 LB159/5 LB159/5-BET HP560 HP567 LB175/21 LB175/21-HP567 H1047R PI3K H1047R HC-4955 LB177/23 LB177/23-mCRPC AR-V7 PROTAC HC-4955 HP518 LB178/24 LB178/24-HP518 AR PROTAC AR HP568 LB179/25 LB179/25-ER PROTAC HP568 GQ1010 7168/9 ADC7168/9-PBI-410 GQ1010 Trop-2 ADC DB-1310 CT168/19 ADCCT168/19-1/2a DB-1310 HER3 ADC/DB-1311 CT165/16 ADCCT165/16-1/2a DB-1311 B7-H3 ADC/HDP-101 CT067/17 ADCCT067/17-BCMA-HDP-101 ASKC202 CT118/26 CT118/26-cMET ASKC202 I BL-M11D1 3139/20 ADC BL-M11D1 CD33 ADC BL-M05D1 3140/21 ADC BL-M05D1 claudin 18.2 ADC AACR 8 AACR tislelizumab CT277/7 CT277/7-BGB-LC-201 NCT05635708 TIS;PD-1+/-NSCLC 2 pamiparib CT125/4 CT125/4-0/2 ociperlimab CT255/14 CT255/14-AdvanTIG-204 2 3 ociperlimab TIGIT+PD-1+cCRT SCLC ociperlimab CT053/3 CT053/3-ociperlimab TIGIT PD-1 1L PD-L1+NSCLC BGB-B167 2371/17 2371/17-BGB-B167 4-1BB/CEACAM5 LBL-007 CT274/4 CT274/4-BGB-A317-LBL-007-202 2 LBL-007 LAG-3 TIS;PD-1 chemo/ESCC 1L LBL-007 CT276/6 CT276/6-Liberty-201 FP-3 LAG-3 LBL-007-1 PD-1 TIS MSS/pMMR CRC pts BGB-10188 CT189/17 CT189/17-1a 3-BGB-10188+tislelizumab PD-1 sintilimab CT266/25 CT266/25-IBI310 2 olverembatinib 1971/20 1971/20-Olverembatinib SDH IBI3001 LB055/16 ADC LB055/16-IBI3001 B7-H3/EGFR ADC IBI334 LB056/17 LB056/17-IBI334 ADCC B7-H3/EGFR IBI343 LB057/18 ADC LB057/18-18.2 ADC IBI343 Cadonilimab CT006 CT006-Cadonilimab G/GEJ COMPASSION-15 3 garsorasib CT246/5 CT246/5 garsorasib KRAS G12C 2 TQB2916 CT192/20 CT192/20-TQB2916 CD40 1 TYK2 2882/13/2882/13-TYK2 niraparib CT169/20 CT169/20-DNA POLQi GSK4524101 ADP-PARP PARPi 1/2 AACR AACR 9 AACR AACR ZL-1310 CT155/6 ADCCT155/6-ZL-1310 Ia/Ib ZL-1218 CT162/13 2024/4/8CT162/13-I CCR8 IgG1 ZL-1218 PD-1 savolitinib CT251/10 CT251/10-Savolitinib(savo)+osimertinib(osi)vs savo+placebo(PBO)in patients(pts)with EGFR-mutated(EGFRm),MET-amplified advanced NSCLC with progression on osi Surufatinib CT266/25 CT266/25-IBI310 2 sovleplenib CT144/23 CT144/23-HMPL-523 Syk JSKN003 CT179/7 ADCCT179/7-JSKN003/I Toripalimab CT113/21 CT113/21-I-B afuresertib CT128/7 CT128/7-LAE005 afuresertib I/II TNBC IMM27M CT097/5 CT097/5-IMM27M Fc CTLA-4 I IMM0306 CT173/1 CT173/1-CD20 B IMM0306 I TST001 CT132/11 CT132/11-I/IIa TranStar101 OSEMITAMAB SKB264 CT038 ADCCT038-2 TROP2 ADC SKB264 MK-2870 G GEJ pts SKB264 CT247/6 ADC CT247/6-2 TROP2 ADC SKB264 MK-2870 NSCLC SKB264 CT282/12 ADCCT282/12-MK-2870-004 MK-2870 SKB264 NSCLC EGFR 3 SKB264 CT283/13 ADCCT283/13-3 MK-2870-007 MK-2870 SKB264 pembrolizumab pembrolizhumab PD-L1 TPS 50%HS-10370 CT119/27 CT119/27-HS-10370 KRAS G12C NSCLC AACR 10 AACR AACR T-1201 CT166/17 XDC CT166/17-T-1201 1 GDC-0570 CT116/24 CT116/24-PIM NB004/GDC-0570 I BC3402 CT185/13 2024/4/9CT185/13-BC3402 I HBW-3220 CT147/26 CT147/26-BTKi HBW-3220/R/R B B-NHL I HR001 CT244/3 CT244/3-HR001/CD19 CAR-T II HRAIN01-NHL01-II DPV-001 CT112/20 CT112/20-DPV-001 PD-1+/-GITR 1 GITRVax ABSK021 LB077/13 LB077/13-ABSK021 CSF-1R KRAS G12C BCMA GPRC5D CD3 LB128/16 LB128/16-BCMA GPRC5D T FORL1 MUC1 ADC LB127/15 ADCLB127/15-FORL1 MUC1 ADC FOLR1low CD38/CD47 LB129/17 LB129/17-CD38 CD47 Tinengotinib LB162/8 LB162/8-FGFR1-3 Tinengotinib ROR1xCD3 LB126/14 LB126/14-ROR1 x CD3 T HH100937 LB031/13 LB031/13-HH100937 SOS1 KRAS/MAPK HH102007 LB032/14 LB032/14HH102007 PARP1 VBC101-F11 LB043/4 LB043/4-VBC101-F11 EGFR/cMet ADC GFH547 LB165/11 LB165/11-GFH547 A RAS(on)CD98 ADC LB425/1 ADCLB425/1-CD98 ADC AACR SHR-4602 ADC AACR11 ADC SHR-4602 SHR-4602 Topo I HER2 ADC HER2 ADC HER2 ADC DS-8201 HER2 SHR-4602 HER2 ADC DS-8201 SHR-A1811 HER2 ADC pertuzumab ER300 HER2 ADC BALB/c JIMT-1 SHR-4602 HER2 HER2 HER2 IC50 0.007 nM 8.21 nM SHR-4602 NCI-N87 ER300 G2/M HER2/SHR-A1811 DS-8201 JIMT-1 SHR-4602 HER2 ADC HER2 HER2 SHR-4602 I NCT05819684 HRA00184-C004 TF AACR TF HRA00184-C004 HRA00184-C004 TF VII TF ADC Tivdak TF ADCHRA00184-C004 TF HRP07132 I Dxh HRP07132 TF VII X HRA00184-C004 HRA00184-C004 TF PDAC HPAFII TF TNBC MDA-MB-231 TF NSCLC H358 TF 6 3 12 mg/kg HRA00184-C004 PK NHP SDP03923-000-9106 LIV-1 ADC AACR SDP03923-000-9106 LIV-1 ADC SDP03923-000-9106 LIV-1 ADC LIV-1 ADC ADC Ladiratuzumab vedotin HR+/HER2-ORR=0%SDP03923-000-9106 LIV-1 ADC LIV-1 I DAR 6 SPR SDP03923-000-9106 LIV-1 SDP03923-000-9106 LIV-1 I LIV-1 ADC DAR=6 LIV-1 SDP03923-000-9106 LIV-1 ADC SDP03923-000-9106 NMPA IND HRA00242-C004 DAR PSMA ADC AACR DAR HRA00242-C004 HRA00242-C004 DAR PSMA ADC PCa AR PCa ADT ADT CRPC PSMA PCa PCa HRA00242-C004 PSMA ADC PSMA IgG1 I DXh HRA00242-C004 PSMA HRA00242-C004 PSMA DAR HRA00242-C004 HRA00130-C004 DLL3 ADC DAR AACR15 HRA00130-C004 DLL3 ADC HRA00130-C004 DLL3 ADC HRA00130-C004 DLL3 ADC I DXh IgG1 DLL3 DMS53 DLL3 U-2OS DLL3 HRA00130-C004 H1184 DLL3 DMS53 DLL3 HRA00130-C004 HRA00130-C004 H1184 DLL3 DMS53 DLL3 3mg/kg 10mg/kg HRA00130-C004 ADC HRA00130-C004 HRA00184-C004 IBI3001 EGFR/B7-H3 ADC AACR16 IBI3001 EGFR/B7-H3 ADC B7-H3 EGFR IBI334 B7-H3/EGFR-bsAb 1 B7-H3 EGFR 2 B7-H3 EGFR Zalutumumab EGFR-mAb Amivantamab c-met/EGFR-bsAb 3 IBI334 120mg/kg/SyntecanE Synaffix IBI334 DAR=4 ADC IBI3001 1 EGFR 2 EGFR-B7-H3-3 ADC B7-H3 EGFR EGFR IBI3001 B7-H3LowEGFRLow B7-H3HighEGFRLlow B7-H3LlowEGFRHigh B7-H3HIGhEGFRHigh EGFR+B7-H3+EGFR-B7-H3-NCI-H508 JIMT-1 BxPC3 NCI-1975 IBI3001 BALB/c PK 282 90 mg/kg/IBI3001 ADC PK IBI3001 EGFR/B7-H3 ADC EGFR/B7-H3 ADC IBI343 CLDN 18.2 ADC AACR17 IBI343 CLDN 18.2 ADC IBI343 Claudin 18.2 ADC CLDN 18.2 ADC CLDN 18.2 ADC IBI-343 CLDN 18.2 ADC ADC IBI-343 T A A Synaffix DAR PK Linker IBI343 ADC IBI343 DNA I AACR2024 IBI-343 I 10mg/kg IBI-343 ADC ADC 2022 I 2022 10 ADC IBI334 EGFR/B7-H3 AACR18 IBI334 EGFR/B7-H3 EGFR EGFR EGFR EGFR/TAA B7-H3 B7 EGFR Innobody B7-H3 EGFR IBI334 IBI334 EGFR B7-H3 B7-H3 IBI334 Zalutumumab EGFR-mAb Amivantamab c-met/EGFR-bsAb EGFR IBI334 ADCC NCI-H358 KRAS-G12C NCI-H292 SK-MES1 SK-MES1-LTC EGFR L858R T790M C797S Amivantamab NCI-H22-EGFRexon20ins 120/75 mg/kg 50%B7-H3/EGFR 120mg/kg IBI334 200 IBI334 B7-H3/EGFR EGFR IBI334 IBI334 ADCC EGFR/B7-H3 BCR-ABL SDH AACR19 BCR-ABL BCR-ABL SDH SDH SDHB GIST SDH GIST SDH SDH Jurkat,clone E6-1,OS-RC-2,RKO,PC12,PC12#5F7 10mg/kg 20 mg/kg QOD 27.4%52.2%20 mg/kg 10 mg/kg Rogaratinib 50 mg/kg SDH SDH BGB-B167 AACR20 BGB-B167 BGB-B167 4-1BB/CEACAM5 BGB-B167 G IgG 4-1BB CEA 4-1BB CD137 CEACAM5 CEA BGB-B167 PBMC CEA CEA 4-1BB BGB-B167 PD-1 BGB-B167 1 SKB264 2L 21 SKB264 2L AACR,TROP2 SKB264 MK-2870 TROP2 ADC I payload-linker pH G/GEJ 2 KL264-01 NCT04152499 2 G/GEJ 5 mg/kg Q2W SKB264 RECIST v1.1 8 2023 11 22 48 9 24 50.0%2L 24 50.0%3L+52.1%3 TRAE 3 TRAE 5%20.8%18.8%12.5%6.3%TRAE ILD/41 ORR 22.0%9 PR 2 DCR 80.5%2L 3L+ORR 27.3%2 15.8%DoR 7.5 3L+pts n=24 54.2%pts 4 14.6m mPFS 3.7m;mOS 7.6 12 OS 32.6%G/GEJ SKB264 OS SKB264 SOC 3L+G/GEJ 3 SKB264 NSCLC 22 SKB264 NSCLC AACR,TROP2 NSCLC NSCLC 5mg/kg Q2W SKB264 NCT04152499 RECIST v1.1 8 2023 11 22 43 NSCLC 17.2 21 EGFR 22 EGFR 30 69.8%3 TRAE 3 TRAE 34.9%30.2%25.6%9.3%7.0%TRAE ILD/EGFRm mPFS 11.5m VS 11.1m SKB264 NSCLC Overall(N=43)EGFR mutant(N=22)EGFR wild typeTotal(N=21)Non-squamous(N=9)Squamous(N=12)ORR,%43.6%60.0%26.3%22.2%30.0%mDoR,m(95%CI)9.3(3.7,10.3)8.7(3.7,10.3)9.6(3.5,NE)/mPFS,m(95%CI)7.2(5.4,11.3)11.5(5.7,12.9)5.3(3.5,6.2)5.8(1.5,12.1)5.1(1.9,9.3)mOS,m(95%CI)22.6(13.1,NE)22.7(19.7,NE)14.1(10.7,NE)16.2(5.8,NE)12.8(3.5,NE)12-mOS rate,%(95%CI)69.0%(52.7,80.7)81.0%(56.9,92.4)57.1%(33.8,74.9)66.7%(28.2,87.8)50.0%(20.8,73.6)18-mOS rate,%(95%CI)56.5%(40.1,70.0)76.2%(51.9,89.3)35.9%(16.0,56.4)44.4%(13.6,71.9)30.0%(7.7,56.9)MK-2870 K 23/MSD MK-2870 K AACR,PD-L1 TPS 50%NSCLC TROP-2 TROP-2 NSCLC MK-2870 SKB264 ADC TROP2 KL610023 NSCLC MK-2870 MK-2870 MK-2870-007 NSCLC PD-L1 TPS 50%MK-2870 614 18 IV NSCLC PD-L1 TPS 50%EGFR ALK ROS1 ECOG 0 1 RECIST v1.1 HIV 1 1 400 mg Q6W MK-2870 4 mg/kg Q2W 18 400 mg IV Q6W 18 ECOG 0 vs 1 TROP-2/OS PFS ORR RECIST v1.1 2023 12 MK-2870 EGFRm NSCLC24/MSD MK-2870 EGFRm NSCLC AACR,TROP-2 NSCLC MK-2870 SKB264 ADC TROP2 KL610023 MK-2870 1 2 EGFR NSCLC 3 MK-2870-004 NCT06074588 MK-2870 EGFR NSCLC III MK-2870-004 556 456 19del L858R EGFR 100 18 III NSCLC 19del 21 L858REGFR ALK ROS1 BRAF V600E NTRK MET 14 RET EGFR 20 S768I 21 L861Q/18 G719X 1 2 TKI PD-L1 EGFR TKI T790M EGFR NSCLC TKI 6 1 15 29 1 1 MK-2870 4 mg/kg Q2W 6 1 22 75 mg/m2Q3W 500 mg/m2Q3W EGFR NSCLC PFS RECIST v1.1 OS ORR DOR PFS OS 2023 11 TROP2 ADC AACR25 TROP2 ADC TROP2 ADC TROP2 TROP2 ADCs TROP2 ADC TROP2 ADC mAbs Trop2 SPR Incucyte CDX TROP2-ADC TROP2 mAbs TROP2 mAb A Trodelvy B Trodelvy B A mAb-a mAb-B KD 6.42nM 0.26nM TROP2 mAb-a/B 0.81nM KD mAbs mAb-A/B TOPi TROP2 ADC ADC AACR26 Disitamab vedotin DV RC48-ADC ADC HER2 HER2 la/mUC ORR 50.5%HER2 la/mUC HER2 HER2 RC48-ADC HER2-ADC RC148 PD-1/VEGF AACR27 RC148 PD-1/VEGF RC148 PD-1 VEGF VEGF TME TME VEGF TME VEGF VEGF 1 PD-1/PD-L1 IgG1 RC148 VEGF PD-1 RC148 VEGF PD-1 TcE AACR28 TcE TcE T cell engager T BiTE T T T TICTE CD3 PD-L1 PD/PD-L1 T BiTE PD-L1 TICTEs TICTE CD3xTAAxPD-L1 T IgG TAA TICTE BiTE xCELLigence RTCA eSight TDCC TICTEs TICTE TICTE PD1/PD-L1 TAAs PD-L1 TAA cMET Her2 Trop2 TICTE BiTE BiTE PD-L1 TICTE TICTE BiTE CRS TICTE XELOX AACR29 PD-1/CTLA-4 XELOX G/GEJ III AK104-302/COMPASSION-15 III OS 610 PD-L1CPS5 49.8%G/GEJ PD-L1 mOS 15.0 vs 10.8 HR 0.62 0.50-0.78 P 0.001 PD-L1 CPS5 mOSNRvs 10.6 HR0.56 0.39-0.80 P 0.001 PD-L1CPS 5 mOS14.8vs11.1 HR0.7 0.51-0.95,P=0.011 CPS1 58.3%64.7%HR0.77 0.51,1.18 PFS ORR DOR mPFS7.0vs 5.3 HR0.53 0.44-0.65 P 0.001 ORR65.2%vs48.9%sNDA NMPA CDE+MET 30+AACR,+vs+EGFR(EGFRm)MET NSCLC AACR 30+N=14+N=16 AE sAE+3(21%)vs 4(29%)+5(31%)3(19%)AE 50%vs 19%36%vs 25%21%vs 31%+MET FISH10+/IHC90+赛沃替尼+奥西替尼 赛沃替尼+安慰剂FISH10+and/or IHC90+a 全患者(N=14)FISH10+and/or IHC90+a(n=7)全患者(N=16)ORR,%(95%CI)b 63(24,91)57(29,82)29(4,71)13(2,38)CRn(%)b 0 0 0 0PRn(%)b 5(63)8(57)2(29)2(13)MDOR周(95%CI)30.6(23.0,NC)30.6(18.9,NC)NR(12.4,NC)NR(12.4,NC)PFS 4(50)9(64)5(71)13(81)中位 PFS,月(95%CI)8.2(4.1,NC)7.4(5.6,NC)4.0(1.3,NC)1.6(1.3,4.1)31 AACR,CT266/25 IBI310 2 14 TEAE 3(21.4%)3 TEAE 7.1%4 TEAE IBI310 NEN AACR数据（2023.04.14-04.19）14例可评价疗效患者85.7%的患者之前接受过全身治疗（50%1L，35.7%2L）9名既往接受过 1 种全身治疗方案的患者ORR 28.6%44.4%DCR 76.8%88.9%中位 PFS 4.15 个月 4.5 个月 HMPL-523 SyK 32 HMPL-523 SyK AACR,HMPL-523在复发难治淋巴瘤患者中的初步疗效41例可评价疗效患者 24例HL患者 7例PTCL患者ORR 26.8%25.0%42.9%DCR65.9%CR 4例(9.8%)，PR 7例(17.1%)，SD 16例(39.0%)66.7%CR 2例(8.3%)，PR 4例(16.7%)，SD 10例(41.7%)42.9%2 CR(28.6%)and 1 PR(14.3%)DOR 未达到 5.7个月(2.0-NR)中位药物暴露时间 2.9个月 HMPL-523 SyK RP2D 700 mg QD 4 1-12 86%CLL BTK 88%HL PD-1 CD30 ADC HMPL-523 HL PTCL:2(HL PTCL 1)18(38.3%)teae 4(8.5%)tee(TRAE)trae 15(31.9%);trae 4(8.5%)3(6.4%)TEAE 23(48.9%)4(8.5%)2(4.3%)TEAE(1)HMPL-506 MLL NPM1 33 HMPL-506 AACR,HMPL-506治疗临床前MLL重排和NPM1突变的急性白血病数据肿瘤生长速率抑制程度 肿瘤退化率5mg/kg 86%-10mg/kg-72%25mg/kg-100%HMPL-506 menin-MLL IC50 menin-MLL HMPL-506 MEIS1 HOXA9 menin-MLL CD11b MLL-r MV-4-11 MOML-13 RS4 11 GI50 3.0 12.1nM CellTiter-Glo NPM1m OCI-AML-3 GI50 22.4nM menin HMPL-506 MLL NPM1 MV-4-11 BALB/c HMPL-506 5 10 25mg/kg HMPL-506 5 mg/kg 28 86%SNDX-5613 50 mg/kg HMPL-506 10 mg/kg 25 mg/kg 72%100%HMA800067 B Dara34 CD38 ADC AACR,临床前B细胞恶性肿瘤模型的数据对比剂量 肿瘤生长速率抑制程度 肿瘤退化率HMA800067 10mg/kg-100%Dara 10mg/kg 20%-40%-HMA800067 CD38+Ramos Dara HMA800067 Dara ADCC ADCP CD38+Daudi Dara ADC HMA800067 CD38 IC50 0.46nM CD38 CD38+HMA800067 CD38-HMA800067 Dara MM RPMI-8226 DLBCL SU-DHL-6 SU-DHL-10 10mg/kg SU-DHL-6 10 mg/kg HMA800067 10 49 10 mg/kg Dara 2 20%-40%BL-M11D1 CD33 ADC AACR35 BL-M11D1 CD33 ADC BL-M11D1:CD33 ADC CD33 AML BL-M11D1 CD33 ADC BL-M11D1 CD33 BL-M11D1 B I Ed-04 Fc Ed-04 S BL-M11D1 DAR=8 BL-M11D1 BL-M11D1 BL-M11D1 CD33 ADC CD33 I BL-M05D1 Claudin 18.2 ADC AACR36 BL-M05D1 Claudin 18.2 ADC BL-M05D1 claudin 18.2 ADC Claudin 18.2 BL-M05D1 Claudin 18.2 ADC BL-M05D1 Claudin 18.2 5103F3 ADCC CDC Fc BL-M05D1 5103F3 B I Ed-04 Ed-04 S BL-M11D1 DAR=8 BL-M05D1 BL-M05D1 MKN-45-Claudin18.2#C11D Patu8988s-Claudin18.2#C7G BL-M05D1 Claudin 18.2 ADC Claudin 18.2 I IL-11 9MW3811 AACR37 9MW3811 IL11 9MW3811 IL-11/IL-11R T PD-1 IL-11 T IL-11 9MW3811 Octet ELISA IL-11/IL11Ra/gp130 IL-11 PD-1 9MW3811 IL-11 IL-11/IL-11R/gp130 TGI 62%9MW3811/PD-1 TGI 45%83%34%75%PD-1 CT26 9MW3811/PD-1 TGI67%9MW3811 T CD8+T/T 9MW3811 I 2MW4991 AACR38 2MW4991 v8 2MW4991 ADCC v8 TGF-1 TME v8 TME TGF-1 2MW4991 TGF-1 v8 Jurkat/h FcRIIIa ADCC 2MW4991 v8 TGF-1 EMT6 CD8+T TME TGF-1 PD-1 v8 v8 100mg/kg TGF-1 v8 TME TGF-1 2MW4991 TME TGF-1 Fc 2MW4691 AACR39 2MW4691 2MW4691 CCR8/CTLA-4 Treg CD8+T CTLA-4 T Tregs CTLA-4 CCR8 CD25 Treg 2MW4691 Tregs CD8+T CTLA-4 RNA Tregs CCR8 CTLA-4 CCR8 CTLA-4 FcRIIIa NK hPBMCs ADCC NSCLC CCR8 CTLA-4 2MW4691 CCR8CCR8/CTLA4 ADCC CTLA-4 ADCC B T CTLA-4 CTLA-4 2MW4691 MC38 hCCR8 hCTLA4 CDX 2MW4691 NHP TYK2 AACR40 TYK2 TYK2 HNSCC TYK2 KO Western blot HNSCC Cal27 Cal27 NT2 guide RNA gRNA TYK2 gRNA TYK2 KO Western blot TYK2 KO JAK1 G2/M TYK2 G2/M TYK2 HNSCC DNA EGFR PACC Exon 20 AACR41 EGFR PACC exon 20 EGFR 3 AST2818 Furmonertinib NSCLC exon 20 FURVENT NCT05607550 FDA PACC NSCLC NSCLC PACC PACC exon 20 AACR GENIE TEMPUS Ba/F3 33 PACC 16 exon 20 PDXs MOE PACC 2.4%20 1.6%EGFR 14%PACC 20 EGFR 10.4%7%p53 PACC exon 20 EGFR NSCLC PACC EGFR PACC Ba/F3/IC50 G719X ex19del+L718V PACC PACC IC50 exon 20 PACC exon 20 L792 P794 exon 20 PACC PACC PACC exon 20 SY-5933 KRAS G12C CT-707 AACR42 SY-5933 FAK SY-5933 FAK KRAS G12C KRAS G12C KRAS G12C FAK FAK KRAS G12C KRAS G12C SY-5933 FAK CT-707 KRAS G12C SY-5933 CT-707 FAK CDX SY-5933 CT-707 CT-707 KRAS G12C FAK SY-5933 DNA-PK SY-7021 AACR43 SY-7021 DNA-PK SY-7021 DNA-PK II DNA DSBs