探索新辅助奥拉帕尼和西地尼布治疗肾癌的机制：肾癌机会之窗（WIRE）临床试验第1至3组的结果.pdf

1、Investigating the Mechanisms of Neoadjuvant Olaparib and Cediranib in Renal CancerResults of Arms 1 to 3 of the WIndow of opportunity in REnal cancer(WIRE)Clinical TrialDr James Jones PhD MRCPWIRE Trial BackgroundBayesian adaptive design,five investigational arms:1.Cediranib,2.Cediranib+Olaparib,3.O

2、laparib,4.Volrustomig,5.Rilvegostomig CI:Professor Grant Stewart NCT03741426Arms 1-3:Patient populationCediranib Cediranib+OlaparibOlaparibn=6(6)n=16(14)n=7(6)Arm 1 Arm 2 Arm 3 Adaptive recruitment(Evaluable patients)CediranibCediranib and OlaparibOlaparibTotalN=6N=16N=7N=29Age(years)Mean(SD)59.2(8.

3、6)62.4(7.3)62.1(8.5)61.7(7.7)Median(IQR)59(54-65)61(57-68)60(55-68)61(56-67)Range48-7152-7550-7548-75SexFemale0(0.0%)1(6.3%)0(0.0%)1(3.4%)Male6(100.0%)15(93.8%)7(100.0%)28(96.6%)Metastatic diseaseM05(83.3%)11(68.8%)5(71.4%)21(72.4%)M11(16.7%)5(31.3%)2(28.6%)8(27.6%)ECOG performance status06(100.0%)9

4、(56.3%)5(71.4%)20(69.0%)10(0.0%)7(43.8%)2(28.6%)9(31.0%)Jones et al AACR 2025Arms 1-3:Primary outcome30%reduction in DCE MRI assessed vascular permeability(median Ktrans)Individual patient median Ktrans changesRepresentative DCE-MRI Ktrans images ScreeningPre-surgeryCase 1Case 2Jones et al AACR 2025

5、Arms 1-3:Secondary outcomesMRI assessed tumour volumeIHC assessed CD8+T cellsAll surgeries were completed within the planned window6.3%(2/29)experienced grade 3 AEExploratory analysisPlasma angiogenic cytokines Defining tumour environments by MRIRebecca Wray,PhD CandidateJones et al AACR 2025Summary

6、 Consistent tumour volume reductions occurred in both cediranib containing arms.Greater induction of PlGF and VEGF-A in the combination arm indicates possible synergy between cediranib and olaparib.Ongoing translational analysis will link tumour environments t