Endpoints and assessments
death, Cancer
ADVERSE EVENT, DISEASE, RECURRENCE, CANCER
The primary study objective was to evaluate clinical activity of the combination regimen; the primary endpoint was objective response rate (ORR) defined as the percentage of patients achieving a radiographic complete response (CR) or partial response (PR), per RECIST v1.1, prior to surgery. With currently available treatments, the percentage of patients with a point in time ORR prior to surgery was assumed to be 5% (null hypothesis) and this rate was thus considered uninteresting. The target percentage of patients with a point in time objective response prior to surgery using sitravatinib and nivolumab was assumed to be 30% (alternative hypothesis). Secondary endpoints were safety; pharmacokinetics (PK) of sitravatinib; immune effects, including changes in programmed cell death–ligand 1 (PD-L1) expression; time-to-surgery; and disease-free survival (DFS). Exploratory endpoints included biomarker analyses of the effect of sitravatinib alone and in combination with nivolumab.Imaging was used for disease assessments, with an allowable window of 4 weeks prior to first study treatment for screening/baseline evaluation and within 1 week of planned surgery for on-study disease assessment. Per protocol, patients would be followed for survival every 6 months from the last study visit for at least 3 years or until death, disease recurrence, or loss to follow-up; disease recurrence was based on off-study imaging assessments performed per standard-of-care for post-nephrectomy patients. AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Data were collected using the Medidata RAVE platform version 2017.2.2.