Glioma drug development benefits from emerging phase 0 and window-of-opportunity trial paradigm.

Clinical drug development is fundamentally difficult for rare and difficult-to-treat solid tumors, for example, glioma. Glioblastoma (GBM), an invariably fatal primary brain tumor, poses a significant challenge in the realm of effective treatments, necessitating an accelerated approach to innovative drug discovery. Investigators keep requiring a process toward obtaining more reliable early-stage signals related to drug activity and a process toward translating those signals into clinical benefits efficiently in late-stage drug development. Besides, these processes could increase the likelihood of benefit in late-stage settings at a lower cost and encourage more opportunities for drug development against other rare and difficult-to-treat cancers. Phase 0 and window-of-opportunity design has been advocated for glioma, aiming to identify and eliminate ineffective therapies early in the specific drug development process, thereby enhancing overall trial quality. However, challenges persist in implementing this trial design including obtaining pre-treatment samples, establishing accurate methodological platforms and biostatistical pipelines, and identifying novel biomarkers based on both clinical and multi-omics information to predict long-term drug responses. In this review, we encapsulate current evidence regarding the window-of-opportunity design in glioma, advocating for its recognition as a standard paradigm in new drug development.