Exposure-Response Analysis to Support Nivolumab Once Every 4 Weeks Dosing in Combination with Cabozantinib in Renal Cell Carcinoma

Purpose: A benefit:risk assessment for a less-frequent nivolumab 480 mg every 4 weeks + cabozantinib 40 mg every day dosing regimen was predicted using modeling and simulation of clinical trial data from nivolumab monotherapy studies and from the nivolumab 240 mg every 2 weeks + cabozantinib 40 mg every day dosing regimen, which demonstrated clinical benefit versus suni-tinib in previously untreated advanced renal cell carcinoma (aRCC) in the phase III CheckMate 9ER trial (NCT03141177). Patients and Methods: Multivariable Cox proportional hazards analyses were conducted using nivolumab monotherapy data in previously treated aRCC and data from CheckMate 9ER to evaluate progression-free survival (PFS), overall survival (OS), and grade >-2 immune-mediated adverse events (IMAE). Results: Nivolumab 240 mg every 2 weeks + cabozantinib versus nivolumab monotherapy showed improvement in PFS (HR, 0.38; 95% CI, 0.31-0.47), OS (HR, 0.63; 95% CI, 0.46-0.85), and 2.67). grade baseline each national poor and OS predictor, predicted cabozantinib lumab every 4 weeks thorn cabozantinib. Conclusions: Comparable benefit:risk was predicted for nivolumab 480 mg every 4 weeksthorncabozantinib and nivolumab 240 mg every 2 weeks thorn cabozantinib.