Statistical analysis
DISEASE, EVENT
The data cutoff date for this analysis was 19 April 2021. The protocol-defined final analysis for the osimertinib-relapsed cohort was to occur after enrollment of 100 patients; however, guidance from health authorities limited enrollment to 45 patients for this first-in-human study, which was opened under a single-agent investigational new drug (IND). Under the direction of health authorities, CHRYSALIS-2 (ORR was calculated as the proportion of patients in the efficacy population who achieved CR or PR as assessed by the investigator using RECIST version 1.1. The null hypothesis for cohort E was ORR ≤25%, and the alternative hypothesis was ORR ≥40%. A sample size of 100 response-evaluable patients, assuming a non-evaluable rate of 10%, was needed for a power of 85% and a one-sided alpha of 2.5%; however, because the study stopped enrollment prematurely, hypothesis testing was not performed. CBR was calculated as the proportion of patients achieving CR or PR or SD for ≥11 weeks, corresponding to two disease assessments.Data were summarized using descriptive statistics. Observed ORR and CBR are presented along with their two-sided 95% CIs. The 95% CIs were calculated using log transformation, assuming the log (survival rate) is a normal distribution. Time to event endpoints were summarized using Kaplan–Meier estimates and presented with their corresponding 95% CIs.