2698 - Radiomic Substudy of a Phase 1b Trial of MW151 for Cognitive Impairment after Hippocampal Avoidant Whole Brain Radiotherapy (HA-WBRT) for Intracranial Metastases
Presenter(s)
Q. S. Zhang1, N. Rammohan2, M. Dorn3, K. Bowen4, V. Shifrin5, T. Parrish6, R. Kehoe7, L. Van Eldik8, and V. Gondi9; 1Department of Radiation Oncology, McGaw Medical Center of Northwestern University, Chicago, IL, 2Department of Radiation Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, 3Northwestern University, Chicago, IL, 4Bluegrass Research Consultants, Inc., Versailles, KY, 5ImmunoChem Therapeutics, LLC, Auburndale, MA, 6Radiology (Basic and Translational Radiology Research), Physical Therapy and Human Movement Sciences, McCormick School of Engineering, Northwestern University, Chicago, IL, 7Northwestern Medicine, Chicago, IL, 8University of Kentucky, Lexington, KY, 9Northwestern Medicine Cancer Center Warrenville and Proton Center, Warrenville, IL
Purpose/Objective(s): Patients with intracranial metastases may receive WBRT for local disease control. WBRT can cause cognitive impairment. MW151 is an oral first-in-class, anti-neuroinflammatory, central nervous system (CNS)-penetrant small molecule. Pre-clinical testing in animal models of CNS disorders including radiation-induced cognitive impairment has shown MW151 to have neuroprotective effects. In this phase 1b first-in-patients trial-in-progress, the primary objective is to determine the safety and tolerability of MW151 in adult patients with intracranial metastases receiving HA-WBRT. A secondary objective is to compare neurocognitive toxicity of trial patients as measured by neurocognitive function (NCF) tests to that of historical control patients treated with WBRT (WBRT alone). The radiomic substudy’s exploratory objective is to estimate the change in predicted brain age after MW151 plus HA-WBRT compared to WBRT alone. The hypothesis is that brain aging effects of WBRT can be prevented with MW151.
Materials/Methods: The eligible patient population includes non-pregnant female or male patients aged at least 18 years with intracranial metastases from solid tumors to be treated with HA-WBRT. In Part A of the study, 10 subjects will receive open label MW151 starting the day before HA-WBRT given 3 Gray (Gy) per daily fraction, Monday through Friday, for 10 fractions. For 28 days, females would receive 10 mg BID, and males would receive 10 mg QD. Subjects would be evaluated for safety at 24 hours prior to continued dosing, and during weeks 1, 2, and 4. Once a Safety Monitoring Committee has reviewed Part A data, an additional 30 patients would be enrolled in Part B, which would involve the same treatments as in Part A. Each patient would be followed for a total of 24 weeks from the start of HA-WBRT and MW151 with safety and tolerability assessments including physical exams, labs, and adverse event reports. NCF tests would occur at baseline and at 2, 4, and 6 months from start of MW151 and HA-WBRT. Standard-of-care brain MRI would be conducted throughout the study. From each brain MRI, open-source software for processing and analyzing brain MRI images would be used to derive brain structure surface data. A deep learning model applied to surface data would predict brain structure age. Regression analysis using longitudinal predicted brain structure age and chronological age would be used to estimate the speed of predicted brain structure aging for patients on trial compared to WBRT alone.
Results: The trial has completed accrual with 23 patients enrolled. Analyses are ongoing and will be finalized during the summer of 2025.
Conclusion: In this phase 1b trial of MW151 plus HA-WBRT, we expect to determine safety and tolerability of MW151 and its preliminary efficacy in lowering the risk of neurocognitive toxicity and/or preventing brain aging associated with HA-WBRT for brain metastases. The trial is registered with ClinicalTrials.gov with identifier NCT05417282.