Citations

e13891 Background: Most patients with central nervous system (CNS) malignancy develop cognitive impairment, fatigue, and mood-related symptoms that are impacted by cancer and treatment, including radiation therapy. We currently have limited therapies to mitigate neurocognitive toxicity. It is important to accurately assess neurocognitive function and symptom burden when working to establish therapeutics. The objective of this trial is to assess the effectiveness of therapies aimed at improving neurocognitive function and quality of life by leveraging a decentralized approach incorporating an established digital neurocognitive assessment tool and development of a remote symptom collection/medication log to improve capture of longitudinal neurocognitive data. Methods: This is an open-label decentralized clinical trial (NCT06377696) that randomizes patients who have received intracranial radiation for primary and secondary brain tumors in a 1:1 allocation to health promotion with a wearable device +/- metformin (targeting radiation-related toxicity). Remote symptom collection is reported through digital patient surveys. Medication adherence is being monitored through a digital medication log developed for the study. Remote neurologic examination is performed by clinical neuro-oncologists at telehealth visits. Participants perform serial remote cognitive assessments with an established digital neurocognitive testing platform – Mayo Test Drive (MTD). Cognitive assessments and symptom surveys were designed to be completed on a smartphone, tablet, or computer device. Results: The study started enrollment on May 31, 2024. As of January 27, 2025, 54 of 100 planned participants have enrolled (27 on each arm). 51 participants remain active on trial; 3 withdrew from trial participation (2 prior to treatment, 1 after treatment). The overall completion rate for a quality-of-life questionnaire (EORTC QLQ-C30) is 85.0%, and each dose of metformin logged is 78.5%. The overall completion rate for virtual neurologic examination and short test of mental status is 94.7%. For MTD, the overall completion rate is 97.9%. The average MTD session duration was 16 minutes. Most participants completed MTD testing using a smartphone (90.5%) at home (89.1%). Conclusions: These results provide preliminary support that a decentralized trial assessing neurocognitive outcomes is feasible in patients with CNS malignancy. The completion rates of questionnaires and objective cognitive evaluation are comparable or higher than expected with historic norms. Final study results will provide real-world cognitive and quality-of-life data for patients with CNS tumors while providing preliminary data on the effectiveness of device-based health promotion +/- metformin for treatment related cognitive decline. Clinical trial information: NCT06377696 .

2053 Background: Recurrent gliomas are highly aggressive brain tumors, often resistant to conventional treatments. Immune checkpoint inhibitors (ICI) have emerged as promising therapeutic agents by targeting tumor cells through immune modulation. However, clinical trials have demonstrated limited efficacy in recurrent gliomas. This study aimed to identify potential factors influencing treatment efficacy of ICIs in recurrent gliomas. Methods: This retrospective study, conducted across the Mayo Clinic following IRB approval, included patients ≥ 18 years diagnosed with adult-type diffuse gliomas. Eligible patients received treatment with at least 2 cycles of ICI for recurrent glioma between 2014 – 2024. Patients treated with ICIs as initial therapy were excluded. Clinical, radiographic, histological, and molecular data were analyzed, with missing information excluded. Responders to ICI were defined as patients who did not meet iRANO criteria for progressive disease based on first radiographic response assessment (and confirmatory follow up imaging as needed for possible pseudo-progression). Survival outcomes [Progression-Free Survival (PFS) and Overall Survival (OS)] and potential predictive variables were analyzed using the Kaplan-Meier method and Cox-Regression Analyses. Results: 67 patients met eligibility criteria (mean age: 45.1 ± 15.0 years; 64.2% male; 94% white). 64 (95.5%) patients received Pembrolizumab, 2 (3%) Nivolumab, and 1(1.5%) combined Ipilimumab/Nivolumab, with a median treatment duration of 2.77 (1.39 – 19.4) months. All had prior alkylating chemotherapy. The OS (from diagnosis) for IDH wildtype (IDH-WT, n = 36), IDH mutant, 1p/19q non-co-deleted (IDH-MUT, n = 17) and IDH mutant, 1p/19q co-deleted (OLIGO, n = 14) gliomas were 3.1, 9.2, and 18.6 years, respectively. The median PFS from time of ICI was 2.23 (0.69 – 27.3) months. 24 (36.9%) patients were identified as Responders. PFS was not significantly different between patients with IDH-MUT and IDH-WT gliomas (2.30 vs 2.07 months, p = 0.593). However, patients with OLIGO gliomas had a significantly higher PFS compared to IDH-WT gliomas (5.16 vs 2.07 months, p = 0.021). The proportion of responders was greatest in OLIGO gliomas, however, did not reach statistical significance (IDH-WT, 31.4%; IDH-MUT, 29.4%; OLIGO, 61.5%, p = 0.120). Overall PFS was not impacted by patient age, sex, and extent of initial resection. When analyses were limited to Responders, the PFS for IDH-WT, IDH-MUT and OLIGO gliomas were 5.75, 7.01 and 10.8 months, respectively ( p = 0.434). Conclusions: Patients with recurrent OLIGO gliomas may have a longer PFS with ICI therapy compared with recurrent IDH-WT and IDH-MUT gliomas. However, there is significant variability in ICI treatment efficacy between patients. Further molecular profiling is in progress to evaluate additional predictive biomarkers of response.

TPS2099 Background: Gliomas are the most common primary central nervous system (CNS) malignancy in adults, accounting for 26.3% of all brain tumors. Care at high volume centers is associated with an overall survival benefit, but access to in-person evaluations can be challenging due to disease-related neurological disability and loss of income. Telehealth represents a convenient and efficient alternative to in-person evaluations, but acceptability and comparative safety of this care delivery modality has not been prospectively evaluated among glioma patients undergoing chemotherapy. Methods: This single-arm non-randomized pragmatic clinical trial evaluates patient satisfaction with, and safety of video-enabled telehealth assessments compared to in-person evaluations for patients with glioma undergoing temozolomide chemotherapy. The study includes adult patients with a diagnosis of glioma requiring adjuvant temozolomide chemotherapy. Participants act as their own controls, alternating between in-person and telehealth assessments while undergoing chemotherapy dosed per standard of care. Monitoring labs are completed locally and transmitted electronically. For participants without access to Wi-Fi or a device (e.g. mobile phone or computer), cellular-enabled tablet devices are provided to facilitate appointments and completion of electronic study components. All participants who travel to in-person appointments are reimbursed for travel expenses. The primary outcome measure is patient satisfaction with care delivered, as measured by institutional Press-Ganey survey scores obtained following telehealth and in-person assessments. A key secondary outcome measure is completion rate of planned oral chemotherapy, tracked using a digital pill diary incorporated into our institutional electronic health record. The digital diary allows real-time tracking of chemotherapy adherence and adverse events experienced by participants. Other secondary outcomes include acute care utilization days following telehealth and in-person visits (defined as emergency department evaluations and days of inpatient stay), neurologic disability as measured by the Neurologic Assessment in Neuro-Oncology (NANO) scale, and disease related quality of life measured by the EORTC QLQ-C30. All participant surveys are self-reported and completed electronically. This decentralized pragmatic clinical trial provides unprecedented, prospective real-world data on utilization of telehealth services compared to in-person visits for patients undergoing chemotherapy for glioma. We expect the data generated to inform the design and conduct of future decentralized interventional neuro-oncology trials. NCT06625047 opened for enrollment in October 2024, 16 of 30 intended participants were accrued as of January 2025. Clinical trial information: NCT06625047 .

TPS2092 Background: Glioblastoma (GBM) is the most common primary brain malignancy in adults. GBM is universally recurrent and associated with dismal outcomes. Re-irradiation (reRT) is ideal for evaluating combination therapy for recurrent GBM (rGBM) due to its multifactorial mechanism of action, including downstream immunomodulatory activity. RT (especially multi-fraction) increases immunogenicity in preclinical models by promoting immune activation, immune migration, and antigen uptake. Additionally, a recent study demonstrated enhanced PD-L1 expression in the glioma tumor microenvironment (TME) following RT, and combining stereotactic RT with a PD-1 inhibitor improved survival in murine models. Retifanlimab is a humanized monoclonal anti-PD1 IgG4 antibody that received FDA approval for adults with metastatic or recurrent locally advanced Merkel cell carcinoma. Bevacizumab, an anti-VEGF antibody, is a treatment for radiation necrosis/cerebral edema with less immune suppression than corticosteroids. In a previous Phase 2 study, hypofractionated RT (HFRT), retifanlimab, and bevacizumab was associated with a 9-month overall survival (OS) rate of 71.4%. To demonstrate the efficacy of this regimen compared to HFRT and bevacizumab, we have designed a new randomized controlled Phase 2 trial. We hypothesize that combination reRT with retifanlimab will produce a more robust anti-tumor immune response and improve OS compared to reRT without retifanlimab. Methods: This is a multicenter, open-label, randomized, controlled Phase 2 study of retifanlimab, bevacizumab, and HFRT for adult patients with rGBM. Patients are randomized 1:1 to the experimental (bevacizumab + retifanlimab + HFRT) or control cohort (bevacizumab + HFRT). Key eligibility criteria include age ≥ 18 years, Karnofsky performance status ≥ 60, ≥ 4 months since administration of any prior bevacizumab, and dexamethasone dose ≤ 4 mg at the time of randomization. The primary endpoint is 9-month OS. Secondary endpoints include OS, progression-free survival, objective response rate, neurologic assessment by NANO criteria, and adverse events profile. Protocol treatment will continue up to two years, or until progression or intolerable toxicity. Survival follow up will continue every two months, up to four years. Seven of the planned 94 patients have been enrolled as of submission on 1/28/25. Clinical trial #: NCT06160206. Funding provided by Incyte. Clinical trial information: NCT06160206 .

Objectives/Goals: Mayo Clinic’s Clinical Trials Beyond Walls™ (CTBW) program collaborates with study teams to implement decentralized elements in clinical trials, enabling participation from home or local settings. In cancer treatment trials, traditional paper pill diaries are replaced with real-time digital tracking solutions to monitor chemotherapy adherence. Methods/Study Population: The CTBW team developed a solution to deliver electronic pill diaries to research participants using the electronic health record (EHR) system Epic and patient portal MyChart1. The solution includes a portal message to remind participants to take chemotherapy. Medication dose, date taken, and reasons for missed doses (e.g., “I forgot” or “side effects were bothersome”) are captured. An automated in-basket notification system alerts the study team when predefined conditions are met. Configurable medication schedules ensure diaries are sent according to the prescribed frequency. Reports were generated to allow study teams to monitor all participant diaries. Results/Anticipated Results: The CTBW team implemented this digital pill diary in neuro-oncology trial NCT066250472. We anticipate the pill diary in the patient portal will enhance chemotherapy adherence by capturing real-time data in a platform widely used by Mayo Clinic patients. This patient-reported data is stored in the EHR, where it is accessible to providers and study teams. This allows for continuous monitoring, which facilitates a streamlined review of potential adverse events, improved compliance visibility, and timely treatment adjustments compared to paper-based or external solutions. The system also streamlines data entry, reducing human error and eliminating manual transcription. The created language and workflow templates allow the CTBW to scale this approach to future cancer trials Discussion/Significance of Impact: Decentralized clinical trial participants may never visit Mayo Clinic, making digital recording essential. The EHR-based digital pill diary enables continuous monitoring within a familiar system for providers and patients, increasing study team visibility, and allowing for earlier intervention in cases of non-compliance or adverse events.