Trial endpoints
tumor
DISEASE, TUMOR
The assessment of response was undertaken using three different radiological response assessment criteria: RANO-HGG criteria, which assess tumor response primarily based on T1-weighted, contrast-enhanced imaging, and RAPNO-LGG and RANO-LGG criteria, both of which assess tumor response based primarily on non-enhancing disease by T2/FLAIR. The characteristics of these different response criteria are summarized in Extended Data Table The primary endpoint in arm 1 was ORR, defined as the proportion of patients with a confirmed response of CR or PR according to RANO-HGG criteria, as assessed by an IRC. Secondary endpoints for arm 1 included CBR, PFS, DOR and TTR, as assessed by the IRC using RANO-HGG criteria. CBR is defined as the proportion of patients with a confirmed response or SD lasting any length of time, 6 months or more or 12 months or more. ORR, CBR, PFS, DOR and TTR were also assessed by the IRC according to RAPNO criteria. Secondary endpoints for safety included evaluation of AEs, laboratory abnormalities and cardiac function assessments (change from baseline in QTcF, PR interval, QRS interval, heart rate or ECG waveform morphology). Post hoc exploratory endpoints for arm 1 included ORR and CBR according to RANO-LGG criteria by IRC assessment. For RAPNO and RANO-LGG ORR assessments, patients with confirmed MRs were considered responders in accordance with published guidelines. Changes in quality of life and health utilities measures were exploratory objectives.