Clinical trial statistical analysis
PD, tumor, SD
DISEASE, TUMOR
This study was a phase 1, first-in-human, dose-escalation and cohort-expansion study designed to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary anti-tumor activity of tebotelimab. The dose escalation at low dose (1 mg, 3 mg and 10 mg) applied to single-patient escalation. Sample size for the dose-escalation phase at 30 mg or higher dose was based on a 3 + 3 design. Additional patients might be enrolled if enrollment to a dose cohort was expanded or intermediate dose cohorts were evaluated in the dose-escalation phase. Sex and/or gender were not considered in the study design.The cohort-expansion phase enrolled separate tumor-specific monotherapy and combination therapy cohorts. Patients who discontinued study treatment before the first planned evaluation might be replaced at the discretion of the sponsor. The sample sizes are primarily based on providing preliminary estimation of ORRs. The planned 16 and 40 patients in a monotherapy expansion cohort would allow estimation of ORR with the standard error <0.13 and <0.08, respectively. The planned 30 patients in a combination expansion cohort would allow estimation of ORR with the standard error <0.10. Using sample sizes of 16, 40 and 30 and assuming a true response rate of 15%, the probability of seeing a response in any of these cohorts was 93%, 100% and 99%, respectively.Two general populations were used for the analysis: the safety population and the response-evaluable population. The safety population is defined as all patients who received at least one dose of study drug. This population was used to summarize baseline, safety, pharmacokinetics and pharmacodynamics data. The response-evaluable population is defined as all patients who received at least one dose of study drug, had baseline measurable disease and had at least one post-baseline radiographic tumor assessment. This population was used for summary of tumor assessment data and analyses of responses. Categorical data were summarized by the number and percent of patients falling within each category. Continuous variables were summarized by descriptive statistics, including mean, standard deviation, median, minimum and maximum. For RECIST version 1.1, the best overall response (BOR) was categorized as complete response (CR), partial response (PR), stable disease (SD), PD or not evaluable (NE). To be qualified as BOR, CR and PR required confirmation at least 4 weeks after initial observation of such response, and SD was required to be observed at least once after 6 weeks from the start of study treatment. The ORR was calculated as the proportion of patients in the response-evaluable population achieving a CR or PR per RECIST version 1.1. A two-sided 95% exact binomial CI for ORR was calculated. Median DoR was estimated using the Kaplan–Meier method. The method of Brookmeyer and Crowley