Exposure–response analyses
EVENTS, EVENT, CPH
For exposure–response analyses of PFS and safety endpoints, the number of patients in the CheckMate 9ER trial with events and the total number at risk are listed in Supplementary Table S3. These patients received at least one dose of nivolumab plus cabozantinib and had a baseline and/or at least one post-baseline assessment of the clinical endpoint as indicated; patients without a measurable PK concentration were assigned population-level PK parameter estimates. The PK parameters were adjusted for covariates in the 12 patients without measurable PK concentrations for population-level exposures. Ten of these patients had a cabozantinib dose modification event or were censored prior to the PK assessment of cabozantinib at Cycle 3. Although using the population level PK estimates for patients without measurable cabozantinib PK could bias the results given early dose modification or censorship, sensitivity analyses were performed that excluded these 12 patients. Parameter estimates and inferences for the sensitivity analyses did not change the results. The VPC plots using the final CPH model parameters for predicting the incidence of the clinical endpoints are provided in Supplementary Figs. S2–S5.