A multicenter, open-label, phase II study of adaptive combination immunotherapy with VEGFR-TKI for advanced renal cell carcinoma.

TPS575 Background: The KEYNOTE-426 trial found superior progression-free survival (PFS) and overall survival (OS) with pembrolizumab plus axitinib versus sunitinib in advanced renal cell carcinoma (RCC). However, current treatment paradigms involve continuous therapy administration for two years or until disease progression, potentially exposing patients to unnecessary treatment burden and quality of life toxicities. Adaptive dosing strategies, which allow for periods of treatment interruption following documented response, may preserve therapeutic efficacy while reducing cumulative toxicity and healthcare costs. NCT06860386 aims to evaluate feasibility and PFS with adaptive pembrolizumab plus axitinib in advanced RCC. Methods: NCT06860386 is a multicenter, open-label, phase II trial evaluating adaptive combination immunotherapy in advanced RCC. The study will enroll 75 patients aged ≥18 years with treatment-naïve, unresectable advanced or metastatic clear cell RCC. Patients will receive pembrolizumab (200 mg every 21 days) plus axitinib (5 mg twice daily) in 9-week treatment cycles. Radiographic assessment using RECIST 1.1 criteria will be performed at baseline and at 9-week intervals. Patients achieving target lesion reduction > 20% from baseline at the first post-treatment assessment will be eligible for adaptive treatment. Upon initiating adaptive treatment, study therapy administration is paused and may be re-initiated when radiographic assessment demonstrates target lesion growth to baseline size or greater. Study therapy may again be paused when target lesion reduction > 20% is achieved per RECIST. Treatment-free intervals and re-initiation cycles are continued until disease progression occurs during active treatment or other discontinuation criteria are met. Primary endpoints include progression-free survival and enrollment feasibility rate, defined as the proportion of patients eligible to proceed to adaptive treatment who consent to participate. Key secondary endpoints include safety, patient-reported outcomes, and cost effectiveness. Clinical trial information: NCT06860386 .