Statistical analyses
death
RECURRENCE, DISEASE, EVENT
It was planned that the study would enroll 25 patients, anticipating that 18 of these would be evaluable for clinical activity. A one-sided (alpha 0.025) Exact test for single proportion was used to test the hypothesis of whether the percentage of patients with ccRCC achieving a point-in-time objective response prior to surgery was ≤5% against alternative hypothesis that the objective response was >5%; the corresponding 95% confidence intervals (CIs) were calculated using the exact Clopper-Pearson method. An efficacy-evaluable population of 18 patients would provide 80% power with a two-sided Type 1 error of 0.05 (equivalent to one-sided alpha 0.025) to demonstrate a significant difference between the target response rate (30%) versus background (5%). Event time was censored on the date of surgery, or date of last follow-up assessment documenting absence of recurrence or death, whichever occurred later for patients who were alive and disease-free. No interim analysis was planned.The efficacy analysis included patients who received ≥1 dose of each study drug and underwent on-study disease assessment prior to surgery. The safety analysis included all patients who received ≥1 dose of either sitravatinib or nivolumab. The PK evaluable population comprised all patients who received sitravatinib and had non-missing concentration-time data. Correlative studies were performed using samples from the enrolled, safety, or efficacy populations, according to the specific analysis being conducted; the number of samples used in each analysis varied according to specimen availability.The primary endpoint of proportion of patients achieving an objective response (CR or PR) was summarised. Information regarding pathologic CR was summarised descriptively. DFS was described using the Kaplan-Meier method. Median follow-up for DFS was calculated using the reverse Kaplan–Meier method. Median extent of follow-up was calculated based on descriptive statistics from first dose to last date known alive.