21Short TeRm intensified pembrolizumab (KEytruda) and tivozanib for Hogh-Risk renal cell carcinoma—STRIKE! (A033201) - NCT06661720

Abstract Background Pembrolizumab (pembro) for one year following resection of localized high risk clear cell renal cell carcinoma (ccRCC) with a phase 3 trial resulted in improvement in relapse free survival and overall survival (Choueiri, NEJM 2024) However, 20% of patients still experience a relapse within 2 years with no biomarker yet identified to predict who will respond to or needs adjuvant therapy. Addition of a tyrosine kinase inhibitor (TKI) to immunotherapy (IO) is a standard of care in metastatic ccRCC but to date no studies have studied the addition of a TKI to IO in the adjuvant setting. Subsequently, STRIKE! Was developed to explore the benefit of 6 months of tivozanib (tivo) to pembro vs pembro alone in the adjuvant setting for resected high risk ccRCC. Methods Patients with a ECOG PS ≤ 2 and histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features who have undergone complete resection of the primary tumor with pathology revealing pT2 grade 4 disease or any grade ≥ T3 or TxN1 are eligible. In addition, patients who developed metastasis within a year of resection and underwent resection, definitive radiation or ablation of solid, isolated, soft tissue metastases (excluding brain and bone lesions) are eligible. Patients will be randomized 1:1 to pembro for 48 weeks with or without the addition of tivo 1.35 mg by mouth daily D1-21 q28D for 6 months. With no limit on dos holds or interruptions of tivo, dose reductions of tivo to 0.89 mg D1-21 q28D or tivo 0.89 mg every other day are allowed. No dose reductions of pembro are permitted. Following baseline imaging to confirm no disease, imaging is performed every 12 weeks for first year, every 16 weeks for 2nd year, every 24 weeks for third year and then annually. Primary endpoint will be disease free survival as assessed by investigator with key secondary endpoint of overall survival. The study will enroll 1040 patients to detect a minimum detectable hazard ratio of 0.67 (24 month DFS 84% in experimental arm) with 90% power. Quality of life analysis will compare global quality of life and fatigue between the two arms while imaging and specimens will be banked for future research. Trial Schema Significance & Vision STRIKE! is the first trial and only trial to explore the role of adding a VEGF TKI to immunotherapy in the adjuvant setting for resected high risk ccRCC. Correlative analysis will be essential to development of biomarkers of minimal residual disease and response to therapy.