Digital monitoring and assessments in patients with glioblastoma.
Authors: Damestani Yasaman , Shi Ruiyang , Li Kai , Melikian Patrice , Haybeck Shelley , Mundy Gregory , Gill Gursharan , Tang Shijie , Sbar Eric , Duncan Tracey , Tamir Sharon , Shacham Eran , Shah Jatin J. , Shacham Sharon , Wen Patrick Y. , Dunbar Erin , Kumthekar Priya , Colman Howard , Aiken Robert , Butowski Nicholas A. 
Published: June 2022

2045 Background: Glioblastoma (GBM) is an aggressive primary tumor with poor prognosis and survival. Patients (pts) experience debilitating symptoms that have a negative effect on quality of life (QoL). A multidisciplinary approach is necessary to facilitate the reduction of morbidity, preserve QoL, and maximize benefits of treatment. Selinexor (SEL) is a first-in class, oral, selective inhibitor of nuclear export that blocks exportin 1 approved for use in multiple myeloma and diffuse large B-cell lymphoma and has shown activity in GBM. Digital measurements in the KING study through wearable sensors and other devices capture actionable daily data at home for improved care, symptom management, and QoL, are reported here. Methods: XPORT-GBM-029 (NCT04421378) is an ongoing phase 1 dose finding study followed by an open-label randomized phase 2, 5-arm trial to evaluate SEL in combination with standard therapies for newly diagnosed and recurrent GBM (n = 350): radiation+SEL /radiation and temozolomide; radiation and temozolomide±SEL; lomustine±SEL; bevacizumab±SEL; tumor treating field±SEL. The study is conducted at 18 sites in the US and Canada. GBM progression is assessed by standard clinical and imaging as well as QoL measurements by novel digital tools. Four parameters to determine the impact on QoL (cognitive function, lateralization, fatigue, sleep) are measured remotely by smartwatch and smartphone to continuously measure activity and sleep, and to complete a cognitive battery at baseline and before each MRI. Results: To date, pts wearing the smartwatch had higher compliance during the day for activity and gait measures compared to night for sleep measures. Younger pts had better compliance. Over the course of SEL treatment, changes were observed in balance (characterized by double support % and walking asymmetry) and activity level (characterized by step count and walking distance). Of the pts who participated in the cognitive battery (CANTAB) tests, 2 pts had a minor change in cognition measures including psychomotor and processing speed, episodic and spatial working memory, and executive function after 2 SEL treatment cycles. Overall, the CANTAB measures are stable, which align with the mRANO (MRI) results. The correlation between the CANTAB cognition measures and MRI data will be evaluated once more clinical data become available. Ongoing analyses will apply machine learning and statistical tools to determine potential correlations between digital and clinical data, such as physical examinations, AEs, Karnofsky scores, mRANO, NANO, KPS, and PRO QoL questionnaires. Conclusions: This is the first demonstration of digital measurement feasibility in a longitudinal study of pts with GBM. Digital measurements for pts with GBM could provide information on the impact of SEL-based treatment and functional outcomes in clinical trials and increase communication between clinicians and pts, thereby improving QoL and care management. Clinical trial information: NCT04421378.