Estimand and Analysis Consideration in a Phase III Study of CAR-T with Delayed Treatment Effect - a Case Study of Lymphoma

• Activity Number: 355 - Contributed Poster Presentations: Biopharmaceutical Section
• Type: Contributed
• Date/Time: Tuesday, July 30, 2019 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Wen Gu*
• Companies: Novartis Pharmaceutical Inc.
• Keywords: CAR-T therapy; estimand; delayed treatment effect; non-proportional hazard; Kymriah; hypothesis testing

Abstract

It is very important to align a trial’s scientific objective with its estimand, including appropriate testing procedures and estimation of effect size. BELINDA is a randomized phase 3 study of tisagenlecleucel (Kymriah) in adult patients with aggressive B-cell Non-Hodgkin's Lymphoma (NHL) who are relapsed or refractory after frontline therapy and eligible to stem cell transplant (SCT). Patients receiving tisagenlecleucel, a chimeric antigen receptor T-cell (CAR-T) therapy, will undergo a unique cell manufacturing process (~4-6 weeks) before the tisagenlecleucel infusion. Similarly in the control arm, patients will receive platinum-based immunochemotherapy followed in responding patients by SCT. This brings attention to the definition of appropriate estimand, hypothesis testing as well as estimation of the treatment effects based on time-to-event endpoints due to non-proportional hazards. In this poster, we will present this case study and focus on the considerations to connect the scientific objective, testing procedure, and estimation under the framework of estimand.