ITM公司用于诊断和治疗透明细胞肾细胞癌（ccRCC）患者的CAIX靶向放射性药物研究：I II期临床试验设计及首次人体CAIX成像.pdf

1、ITMsITMs InvestigationalInvestigational CAIXCAIX-targetedtargetedRadiopharmaceuticalsRadiopharmaceuticals forfor Diagnosis and Diagnosis and Treatment Treatment ofof Patients with Patients with ccRCCccRCC:Ph I/II Trial Design and First-in-Human CAIX ImagesRobert AwadallahITM-94 and ITM-91 are design

2、ed to target CAIX for Diagnosis and Treatment of clear cell Renal Cell Carcinoma(ccRCC)Choueiri,NEJM,2024;Klatte,Cancers,2009;Feldtman,ASCO 2023;image modified from Aldera,J Clin Pathol 2021https:/ 06/06/2025 and modified,presented by M.Hofman,ASCO,2025)CAIX is involved in pH regulation and induced

3、under hypoxic conditions85-90%of ccRCC express CAIX due to HIF activation as a result of VHL tumor suppressor lossITM-91 and ITM-94 specifically target CAIX being investigated for potential use in therapy and imaging of ccRCCHypoxiaccRCCccRCCTranscriptionHIF-1CytoplasmHIF-1VHLDegradationCAIXHCO3-Fic

4、ation ofcellular pHLoss of cellularadhesionIncreased tumorcell migrationVHLNucleusHIF:Hypoxia-inducible FactorVHL:von-Hippel-Lindau Phase I/II Trial Design(NCT:05706129)ITM-91(177LuLu-DPI-4452)/ITM-94(68GaGa-DPI-4452)EXCLUSION ZONAdapted from Feldman D et al.,TIP Poster ASCO 2023.Journal of Clinical

5、 Oncology.Volume41,Number16_suppl https:/doi.org/10.1200/JCO.2023.41.16_suppl.TPS3160Abbreviations:CRC:colorectalcancer;ccRCC:clearcell renal cell carcinoma;IDRM:intermediate Renal Mass;MTD:Maximum Tolerated Dose;PDAC:pancreatic ductaladenocarcinoma;PET:positronemissiontomography;RP2D:recommended Ph

6、ase 2 dose;SoC:Standard ofCarePhase I First-in-Human ITM-94 ccRCC Imaging Results:Tumor-specific uptake from 15 min after tracer injection Tumor-specific uptake was observed as early as 15 min after tracer injection Study showed specific tumor uptake was sustained for all time points assessed(15 min