EXACT：一项随机 II 期试验评估 XL092（Zanzalintinib）联合免疫疗法治疗接受辅助治疗后病情进展的透明细胞肾细胞癌患者的疗效 (NCT06863311).pdf

1、EXACT:Randomized Phase II Trial of XL092 in Combination with Immunotherapy in Patients Who Progress on Adjuvant Therapy in Clear Cell RCCKarie Runcie,Rana R.McKay,Eric A.Singer,Elshad Hasanov,Jennifer King,Melissa A.Reimers,Ian Okazaki,Alexander Wei,Mark N.SteinRationaleEXCLUSION ZONE In KEYNOTE 564

2、,at 57 months of follow-up:30%of patients on adjuvant pembrolizumab had disease recurrence(15.5%with local recurrence and 88.8%with distant recurrence).1 There is no standard regimen for patients who progress on adjuvant pembrolizumab.Zanzalintinib is a novel oral multikinase inhibitor which has dem

3、onstrated safety,antitumor activity and immunomodulatory effects in treatment-refractory clear cell RCC.2 Phase III studies planned1.Choueri T,et al.N Engl J Med 2024;390:1359-13712.Pal S,et al.ASCO 2024.Abstract 4545(poster presentation)3.Lamb,P et al.AACR-NCI-EORTC Virtual International Conference

4、 on Molecular Targets and Cancer Therapeutics,October 7-10,2021(Virtual Poster Presentation)MC38 mouse colon carcinoma model3EXACT Trial NCT06863311KEY ELIGIBILITY CRITERIA Measurable disease by RECIST Progressed on adjuvant pembrolizumab No prior Zanzalintinib ECOG 0-1Zanzalintinib 100mg po dailyZa

5、nzalintinib 100mg po daily+Nivolumab 480mg IV1:1N=33Primary endpoint:ORRSecondary endpoints:PFS,OS,AEExploratory endpoints:%change in ctDNA,change in immune cells,radiomics and tumor kinetic analysisN=33ImpactEXCLUSION ZONE Zanzalintinib+/-nivolumab may inform future phase 3 studies for patients who progress on adjuvant pembrolizumab Pre-and post-treatment blood and tissue correlates may identify mechanisms of IO resistance in advanced ccRCC Answer the question of IO rechallenge after adjuvant pembrolizumab