Statistics
pre‐dose, BOR, BOR ≤
EVENTS
The sample size calculation was based on Simon's two‐stage design with early futility analysis to test the null hypothesis (BOR ≤ 5%) against the alternative hypothesis (BOR ≥ 20%). With a one‐sided alpha of 5%, 27 patients were required to reject the null hypothesis with 80% power. To allow for a dropout rate of 10%–15%, 32 patients per cohort were targeted for enrollment. Evidence of potential clinical activity would be concluded if at least four patients in a single cohort responded to study treatment.The number and percentage of responders (i.e., confirmed CR or PR), with the corresponding two‐sided Clopper–Pearson 90% confidence intervals (CIs), were provided for the primary efficacy endpoint. Time‐to‐event measures were analyzed using the method of Kaplan–Meier; medians and two‐sided 95% CIs were provided when applicable. AEs were summarized using standard frequency tables (number and percentages of patients with events). For patients receiving T‐DM1 2.4 mg/kg qw, blood samples for the pharmacokinetic assessments were drawn during cycle 1 (pre‐dose and 15–30 min post‐dose on Days 1, 8, and 15), cycle 2 (pre‐dose on Day 1), and cycle 4 (pre‐dose and 15–30 min post‐dose on Day 1). For patients receiving T‐DM1 3.6 mg/kg q3w, blood samples were drawn during cycle 1 (pre‐dose and 15–30 min post‐dose on Day 1), cycle 2 (pre‐dose on day 1), and cycle 4 (pre‐dose and 15–30 min post‐dose on Day 1). All efficacy and safety analyses were based on the safety population (patients who received ≥1 dose of T‐DM1). Statistical analyses were performed using SAS version 9.2 or higher. The last patient's last visit occurred April 10, 2018, and the database was locked June 8, 2018.