Trends in Efficacy Endpoints in Phase II Glioblastoma Trials: A Regulatory Science Analysis (FY2020–FY2022)

Background: /Objectives: In clinical trials for glioblastoma, efficacy evaluation often deviates from the standard Response Evaluation Criteria in Solid Tumors (RECIST) due to the unique characteristics of brain tumors. This study aimed to analyze recent trends in efficacy endpoint settings for Phase II glioblastoma trials conducted during fiscal years (FY) 2020–2022 and compared them with trials from FY2017–2019. Methods: Using Clarivate’s Cortellis™ Clinical Trial Intelligence database, 116 Phase II glioblastoma trials initiated between April 2020 and March 2023 were identified. After applying exclusion criteria, 88 trials were analyzed. Trial characteristics, primary endpoints (PEs), secondary endpoints (SEs), and efficacy designs were summarized and compared to prior data. Results: Among the 88 included trials, approximately half targeted newly diagnosed glioblastoma patients, and the majority tested pharmaceutical products. Progression-free survival (PFS), overall survival (OS), and PFS rate were the most common PEs, whereas OS and quality of life dominated SEs. Time-to-event outcomes were employed in approximately 75% of the trials, whereas objective response rate (ORR) was used as a PE in only 8%, significantly less than in FY2017–2019 (p = 0.022). Randomized, double-blind trials tended to have more PEs but fewer SEs. Conclusions: The diversity of efficacy endpoint settings increased in recent glioblastoma trials, with reduced reliance on ORR as a PE compared to earlier periods. These trends reflect evolving strategies to address the unique challenges of glioblastoma treatment and evaluation.