Mrugała, Maciej M.

Abstract WSD0922-Fu is an oral, central nervous system (CNS)-penetrant, small molecule, ATP non-competitive, reversible EGFR inhibitor which potently inhibits EGFR aberrations specific to non-small cell lung cancer (NSCLC) and high-grade astrocytoma (HGA). MC1914 (NCT04197934, sponsored by Wayshine Biopharma and FDA OOPD) is a first-in-human phase 1 dose-escalation trial investigating the safety and tolerability of WSD0922-Fu in patients with EGFR aberrant recurrent HGA and NSCLC. Adult patients with either recurrent EGFR mutant NSCLC with CNS metastases or recurrent EGFR mutant and/or EGFR amplified HGA were initially treated with oral WSD0922-FU, with doses escalated in cohorts based on a standard 3 + 3 design to determine the maximum tolerated dose (MTD). After establishing the MTD, this trial has now activated three dose expansion cohorts. Two of these cohorts evaluate different dose/schedule strategies in independent populations. The NSCLC cohort includes patients with EGFR mutant NSCLC and CNS metastases, and examines the safety, tolerability, plasma pharmacokinetics and preliminary efficacy of continuous WSD0922-Fu dosing (twice daily, seven days per week). The HGA cohort includes patients with EGFRvIII mutant HGA at first recurrence after prior radiation/temozolomide and examines the impact of higher doses of WSD0922-Fu administered intermittently (twice daily, five days per week). The HGA cohort also includes a food-effect study which evaluates the effect of the fed and fasted states on plasma PK. The third cohort (Brain tumor penetration cohort) includes patients with HGA (any EGFR mutation and/or EGFR amplification) who need a surgical resection for recurrent disease. Patients enrolled will be treated pre-operatively with WSD0922-Fu for five days, and tumor PK/PD will be examined in samples obtained from image-registered brain tumor biopsies. WSD0922-Fu therapy will be resumed after post-operative recovery. Patient enrollment to all three dose expansion cohorts is ongoing.

Abstract BACKGROUND TTFields are electric fields that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. TTFields therapy is approved for adults with recurrent (r) and newly diagnosed (nd) glioblastoma (GBM), based on the phase 3 EF-11 (TTFields 200 kHz) and EF-14 studies (TTFields therapy 200 kHz + temozolomide), respectively, which showed clinical benefit without increase in systemic adverse events (AEs). Pediatric patients were not included in the EF-11 and EF-14 studies. Here, we present pediatric safety data from an updated global post-marketing surveillance (PMS) analysis of patients with brain tumors treated with TTFields therapy, over an 11-year timeframe. METHODS Unsolicited PMS data from patients with brain tumors who received TTFields therapy from October 2011-March 2022 in North America, Europe, Middle East, Africa, and Japan were included. AEs were categorized using MedDRA version 25.1. RESULTS Overall, 25,898 patients were included. Diagnoses were ndGBM (68%), rGBM (26%), anaplastic astrocytoma/oligodendroglioma (4%) and other (2%). Two-thirds of patients were male. The analysis included 93 (0.4%) pediatric/adolescent patients (<18 years). In pediatric patients, 62% experienced ≥1 AE, with 53% related to TTFields therapy; these values were comparable with the overall population (73% and 56%, respectively). The most common treatment-related AEs in pediatric patients were: skin reaction (39%), heat sensation (14%), and headache (12%); and in the overall population were: skin reaction (43%), electric sensation (14%), and heat sensation (12%). CONCLUSIONS This long-term, global, real-world data analysis, including pediatric patients with brain tumors, demonstrates a tolerable safety profile of TTFields therapy, consistent with pivotal clinical studies. There were no major differences in AEs between pediatric and adult patients and no new safety signals identified in the pediatric population. Consistent with the overall dataset, most AEs in pediatric patients were localized mild–moderate skin events, which are typically easily managed.

Abstract Meningiomas are the most common primary intracranial tumor. They are slow growing and often incidentally found tumors that arise from the arachnoid villi. As they grow, they have a greater likelihood of becoming symptomatic with seizures being one of the most clinically significant symptoms. Seizures are more likely to present as a symptom of larger meningiomas and meningiomas that compress cortical areas particularly those in non-skull base locations. These seizures are often managed medically, utilizing the same anti-seizure medications that are used to treat other causes of epilepsy. We discuss common anti-seizure medications used including valproate, phenobarbital, carbamazepine, phenytoin, lacosamide, lamotrigine, levetiracetam and topiramate and their common adverse effects. The goal of pharmacotherapy for seizure control is to maximize seizure control while minimizing the adverse effects of the medication. The decision to provide medical management is dependent on individual seizure history and plans for surgical treatment. Patients who did not require seizure prophylaxis before surgery are commonly prescribed seizure prophylaxis postoperatively. Symptomatic meningiomas not controlled by medical management alone are commonly evaluated for surgical resection. The efficacy of surgical resection in providing seizure freedom is dependent on several features of the tumor including tumor size, the extent of the peritumoral edema, the number of tumors, sinus infiltration and the degree of resection.

3109 Background: WSD0922-Fu is an oral, central nervous system (CNS)-penetrant, small molecule, ATP non-competitive, reversible EGFR inhibitor which potently inhibits EGFR aberrations specific to non-small cell lung cancer (NSCLC) and high-grade astrocytoma (HGA). We report initial results of a first-in-human phase 1 dose-escalation trial (NCT04197934) in patients with EGFR aberrant recurrent HGA and NSCLC. Methods: Adult patients with either recurrent EGFR mutant NSCLC with CNS metastases or recurrent EGFR mutant and/or EGFR amplified HGA were enrolled. WSD0922-Fu was orally administered, and dose escalated in cohorts based on a standard 3+3 design to determine the maximum tolerated dose (MTD). Toxicities were graded per CTCAE v5.0 and preliminary efficacy was based on modified RANO criteria or RECIST 1.1 as appropriate. Results: 25 patients (17 HGA, 8 NSCLC) were enrolled and treated in six cohorts (40 mg once daily to 320 mg twice daily, 28-day cycles). The median age was 57 years (range 39-75 years). 24% were female and 36% were ECOG 0. For patients with HGA, all patients were previously treated with radiation and temozolomide; the median number of prior lines of systemic therapy was 1 (range 1-4). For patients with NSCLC, all patients were previously treated with an EGFR inhibitor (prior osimertinib 88%); the median number of prior lines of systemic therapy was 1.5 (range 1-6). The median duration of exposure to WSD0922-Fu among all patients was 54 days (range 2-258 days). The most common (≥25%) treatment-related adverse events included fatigue (68%), acneiform rash (68%), diarrhea (52%), nausea (48%) and pruritis (28%). The frequency of severe AEs was dose dependent. The most common Grade 3+ AEs (≥10%) included lymphopenia (16%), acneiform rash (12%), headache (12%) and diarrhea (12%). The MTD was defined as 160 mg twice daily. At Cycle 1 Day 15 for patients treated at this dose level, the mean terminal elimination half-life (%CV) in the plasma was 31.6 h (102%) (median 14.5 h; range 6.2-78.7 h). The mean Cmax, Tmax, oral clearance at steady state, and AUC (0-12 h) (%CV) were 4513 ng/mL (50%), 2.0 hr (69%), 6.9 L/hr/m2 (42%), and 28084 h*ng/mL (52%), respectively. Oral clearance at steady state was inversely related with dose, suggesting either inhibition or saturation of clearance processes. Among patients treated at MTD or higher dose levels and with available response data, 100% (5/5) of patients with NSCLC demonstrated clinical benefit (SD + PR) while 60% of patients had partial responses (intracranial and extracranial). Furthermore, prolonged stable disease (9 cycles) was observed in a patient with EGFRvIII mutant GBM. Conclusions: The MTD for WSD0922-Fu monotherapy is 160 mg BID. Preliminary efficacy was observed in patients with osimertinib-resistant NSCLC and EGFRvIII mutant HGA. Enrollment to expansion cohorts is ongoing. Clinical trial information: NCT04197934 .

TPS2081 Background: Murine double minute 2 (MDM2) directly regulates the stability of the tumor suppressor p53, and dysregulation of this pathway can critically disrupt cellular response to genomic stress and lead to cell death. BI 907828 is a highly potent inhibitor of the MDM2-p53 interface that triggers accumulation of p53 and subsequent apoptosis in multiple GBM patient-derived xenografts (PDXs) with wild-type p53. Moreover, the combination of BI 907828 and radiotherapy provides significant survival extension in multiple orthotopic GBM PDXs. Methods: An integrated Phase 0/1 trial design is being used to evaluate the potential for BI 907828 to achieve a therapeutic concentration in brain tumor tissue and to test the safety of the combination with radiation. The co-primary endpoints for the Phase 0 study are i) measured total concentration of BI 907828 and ii) calculated unbound concentration of BI 907828 in contrast and non-contrast enhancing regions of tumor. Key inclusion criteria for the Phase 0 study are patients at least 18 years of age, ECOG performance status of 0 or 1, histologic or radiologic new diagnosis of GBM, and planned surgical resection. The first approximately 6 patients enrolled in the Phase 0 will be treated at the starting dose of 30 mg, and the future patients enrolled will be dosed at higher levels (45 mg or 60 mg) provided there are no safety concerns. If dose-limiting toxicities (DLTs) are encountered, then a Bayesian Logistic Regression Model (BLRM) with overdose control will be used to guide the dose level decisions for the additional patients. Multiple, image-registered tumor samples and intra-operative plasma samples will be analyzed for BI 907828 by LC-MS/MS. Intra-tumoral variation in BI 907828 will be correlated with pharmacodynamic effects of MDM2 inhibition (elevation of p53, p21, MDM2, GDF15, PUMA). Those patients completing the Phase 0 study and who meet additional eligibility criteria can enroll on the Phase 1a portion of the study. The pathologic inclusion criteria are TP53 wild-type, IDH1/2 wild-type, MGMT unmethylated GBM. Co-primary endpoints for the Phase 1a trial are i) occurrence of DLTs during and within 21 days after completion of radiation therapy, and ii) occurrence of adverse events throughout the treatment period. Tolerability of inter-patient dose-escalation of BI 907828 (30, 45, 60 mg) combined with radiation therapy (60 Gy in 30 fractions) will be evaluated with dose-escalation guided by a two-parameter BLRM with overdose control. Patients will remain on BI 907828 monotherapy following completion of radiotherapy until progression. To date, two patients have enrolled on the Phase 0 study, and one patient went on to enroll on the Phase 1a portion of the study. Clinical trial information: NCT05376800 .

2049 Background: Glioblastoma (GBM) has a poor prognosis. Standard treatments are associated with systemic toxicity, further increasing the disease burden in this patient population. Tumor Treating Fields (TTFields) are electric fields that disrupt cancer cell processes which affect cancer cell viability, and are generated by a portable, wearable device which is locoregional and noninvasive. TTFields therapy was approved by the FDA for the treatment of newly diagnosed (nd) and recurrent (r) GBM based on the phase 3 EF-14 (TTFields therapy 200 kHz + temozolomide) and EF-11 (TTFields 200 kHz) studies, respectively. TTFields therapy is also approved for pleural mesothelioma. We report an updated global, post-marketing surveillance (PMS) safety analysis of patients with CNS malignancies treated with TTFields therapy over an 11-year timeframe. This analysis represents the largest dataset of TTFields therapy use to date. Methods: Unsolicited safety data were collected from routine post-marketing activities for patients (N = 25,898) in North America, Europe, Middle East and Africa and Japan, from October 2011 to March 2022. AEs were stratified by diagnosis, age, and sex and categorized using MedDRA version 25.1. Results: Diagnoses were ndGBM (68%), rGBM (26%), anaplastic astrocytoma/oligodendroglioma (4%) and other (2%). Baseline demographics were reflective of real-world practice: median (range) age was 59 (3–103) years; two-thirds of patients were male. Most (69%) patients were 18–65 years; 0.4% were < 18 years, and 30% were > 65 years. All-cause and TTFields-related AEs occurred in 18,798 (73%) and 14,599 (56%), patients, respectively. The most common device-related AE was skin reaction (43% patients overall). There were no major differences in occurrence of this AE between pediatric, adult, and elderly groups (39%, 42%, and 45%, respectively), or between males and females (41% and 46%, respectively). The incidence of device-related skin reactions was higher in ndGBM than rGBM (46% vs 34%, respectively), in line with previous reports. Only 405 (2%) of patients overall reported an AE of treatment-related ‘quality-of-life decreased’. In line with the phase 3 studies, there were no treatment-related systemic AEs. Conclusions: In this updated global PMS safety analysis, TTFields therapy demonstrated a tolerable safety profile in patients with CNS malignancies, with no new safety findings. In line with previous real-world and clinical data, most AEs were localized, non-serious skin events, which were consistent between age groups. Such events can typically be managed easily using prophylaxis and topical therapies, together with optimization of caregiver techniques. Importantly, no TTFields therapy-related systemic AEs were detected.

2002 Background: Elderly patients with glioblastoma have a poor prognosis with phase III trials reporting median overall survival (OS) and global time to deterioration of 6–9 and 1.2 months respectively. 18F-DOPA (3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine) positron emission tomography (PET) is sensitive and specific for identifying regions of high density and biologically aggressive glioblastoma. Proton beam therapy (PBT) can spare more healthy tissue that may improve quality of life for this patient population. With improved targeting of disease along with dosimetric advantages of PBT, this phase II trial tested whether hypofractionated PBT can offer both improved survival and quality of life. Methods: Patients with newly diagnosed glioblastoma aged ≥65 years without contraindications to 18F-DOPA were eligible. Target volumes were defined by PET (tumor/normal brain SUV ≥2.0) and MRI areas of contrast enhancement including surgical cavity. Patients received dose escalated hypofractionated PBT of 35-40 GyE to PET/MRI over 5-10 treatments with 10 mm margin. Patients received concurrent/adjuvant temozolomide. With an alpha of 0.1, 18 of 39 patients would be required to be alive at 12 months for the study to be considered a success. Kaplan-Meier/Cox regression analysis was performed for progression free survival (PFS) and OS. Toxicities were evaluated with CTCAE v4.0. Patients completed EORTC BN20, QLQ-C30, and MMSE questionnaires. Time to deterioration, defined as a 10-point decrease in the score of the function domain or 10-point increase in score of symptom domain, was evaluated. Results: Between 5/2019-6/2021, 43 patients were enrolled, with 4 patients withdrawing due to progression/insurance denial prior to beginning protocol therapy. The median age was 70.2 yrs. and median follow-up was 12.5 months. MGMT methylation was present in 13 (33%). Tumors were multifocal in 10 (26%) and unifocal in 29 (74%). The primary endpoint was met with median PFS/OS was 6.5/12.9 months for all patients and for MGMT methylated patients 11.9/29.8 months respectively. Grade 3 baseline adjusted treatment related adverse events included 1 (3%) confusion, 2 (5%) fatigue, and 1 (3%) seizure. There were no grade 4/5 events. Multivariate analysis revealed MGMT unmethylated, ECOG 2 and biopsy only patients had worse survival. PET volume was more predictive than MRI volume for OS with PET volume>26 cc having a hazard ratio of 3.7. The median time to global deterioration per QLC-C30 was 6.3 months. Conclusions: This phase II trial incorporating 18F-DOPA PET-guided dose escalated hypofractionated proton beam treatment for elderly patients with glioblastoma met its primary endpoint for improved OS and patient reported quality of life compared to historical controls. Further investigation is warranted. Clinical trial information: NCT03778294 .

Abstract High grade glioma (HGG) represents a group of devastating diseases with dismal prognosis. Surgical resection of the contrast enhancing (CE) region of HGG remains the mainstay of treatment, but recurrence inevitably arises from the unresected non-contrast enhancing (NE) region, surgically inaccessible due to cancer cell invasion into healthy brain tissue. Due to its critical role in recurrence, understanding of the NE region is central to the improvement of clinical outcomes. We reveal the biological characteristics of this region through image localized multi-regional sampling. We linked microenvironmental characteristics measured by multi-parametric MRI to genomic mutations and transcriptional phenotypes using mixed effect modeling which allowed us to control for individualized patient effects. We first confirmed that T2 is a significant indicator of IDH mutation status in the NE region, being the first description of such a relationship in a HGG cohort. We found the combination of EGFR amplification and CDKN2A homozygous loss was associated with a significantly lower mean diffusivity (MD) compared to double wild type tumors in the NE region, indicating the presence of greater cellular packing and proliferation in EGFR amplification/CDKN2A loss regions. Finally, using single cell pathway based tumor classifications, we showed that nK2, a DSC-MRI metric representing cell size heterogeneity, correlated positively with neuronal signature and negatively with glycolytic/plurimetabolic signature within the NE tumor, indicating that glycolytic/plurimetobolic tumors possessed a high amount of cell size heterogeneity compared to neuronal samples. This hypothesis was supported using digital reference object (DRO) modeling which confirmed that cell size and heterogeneity drove the differential nK2 signal between neuronal and glycolytic/plurimetabolic samples. We identified immune cell infiltrate as one possible mechanism of increased cell size heterogeneity using transcriptomic signature analysis which found more immune cell signatures within glycolytic/plurimetobolic tumors compared to neuronal. Collectively this study demonstrates the central role of multi-parametric MRI as a non-invasive measure of tumor biology and a tool for understanding the clinically critical NE region which can then inform new therapies targeting this region of HGG recurrence. Citation Format: Matthew Flick, Taylor Weiskittel, Kevin Meng-Lin, Fulvio D'Angelo, Francesca Caruso, Shannon Ensign, Mylan Blomquist, Luija Wang, Christopher Sereduk, Gustavo De Leon, Ashley Nespodzany, Javier Urcuyo, Ashlynn Gonzalez, Lee Curtin, Kyle Singleton, Aliya Anil, Natenael Simmineh, Erika Lewis, Teresa Noviello, Reyna Patel, Panwen Wang, Junwen Wang, Jennifer Eschbacher, Andrea Hawkins-Daarud, Pamela Jackson, Kris Smith, Peter Nakaji, Bernard Bendok, Richard Zimmerman, Chandan Krishna, Devi Patra, Naresh Patel, Mark Lyons, Matthew Neal, Kliment Donev, Maciej Mrugala, Alyx Porter, Scott Beeman, Yuxiang Zhou, Leslie Baxter, Christopher Plaisier, Jing Li, Hu Li, Anna Lasorella, Chad Quarles, Kristin Swanson, Michele Ceccarelli, Antonio Iavarone, Nhan Tran, Leland Hu. Multi-parametric MRI maps regional heterogeneity of high grade glioma phenotypes. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5621.

Abstract High grade gliomas (HGG) are aggressive primary brain malignancies typified by diffuse invasion, genetic heterogeneity, and a universally fatal outcome. MRI-defined contrast-enhancing (CE) tumor burden serves as the clinical standard that guides maximal surgical resection and post-therapy response assessment. However, HGGs also comprise an invasive non-enhancing (NE) tumor margin that extends beyond the CE core and harbors the cells that contribute to recurrence. Sampling restrictions have hindered the comprehensive study of these NE HGG cell populations driving tumor progression. Herein, we present an integrated multi-omic analysis of 313 spatially matched multi-regional CE and NE tumor biopsies from 68 HGG patients, performing whole exome and RNA sequencing of both IDH wild-type and IDH mutant HGGs. We report spatially restricted molecular profiles in IDH-mutant HGG, highlighting a concern for sampling bias given the importance of molecular diagnosis and prognostication in IDH-mutant HGG. Regardless of IDH status, we found that NE tumor regions harbored the highest proportion of private mutations, which reflects an increased development of regional genomic complexity in infiltrative tumor. The multiregional genomic profiling of our IDH wild-type HGG cohort reveals that EGFR and NF1 somatic alterations occur as mutually exclusive events in 98.7% of tumors. However, we resolved rare low allele frequency co-alterations of EGFR and NF1 within the NE region. We find this co-occurrence enriched in recurrent tumors, pointing to the early emergence of NF1 inactivation in the NE regions. We constructed genomic models predictive of recurrent disease from both NE and CE regions, which highlight the occurrence of clonal EGFR copy number alterations and NF1 loss as clonal or subclonal events, respectively, emphasizing the regional and temporal complexity of well-studied canonical driver alterations. We detailed the spatially unique acquisition of multiple distinct EGFR alterations giving rise to intra-tumoral EGFR mosaicism, a challenge in the implementation of EGFR directed therapies. Our study also identified two transcriptomic clusters delineated by the significant overrepresentation of neuronal (NEU) and glycolytic/plurimetabolic (GPM) pathway-based functional states in the NE region. NE regions of the NEU subtype harbor the greatest proportion of private mutations, suggesting these infiltrative tumor cells accumulate alterations without clonal expansion. GPM populations conversely displayed a less branched phylogeny and were transcriptionally enriched in immune cell signatures. This phenotypic dichotomy between GPM and NEU populations supports the growing body of evidence that invasive GBM cells either take on a neuronal phenotype for active invasion or a more metabolic phenotype involving interaction with astrocytes, other glial cells, and infiltrating immune cells. Citation Format: Mylan R. Blomquist, Leland S. Hu, Fulvio D'Angelo, Taylor M. Weiskittel, Francesca P. Caruso, Shannon P. Fortin Ensign, Christopher Sereduk, Gustavo De Leon, Lee Curtin, Javier Urcuyo, Ashlynn Gonzalez, Ashley Nespodzany, Teresa Noviello, Jennifer M. Eschbacher, Kris A. Smith, Peter Nakaji, Bernard R. Bendok, Richard S. Zimmerman, Chandan Krishna, Devi Patra, Naresh Patel, Mark Lyons, Kliment Donev, Maciej Mrugala, Alyx Porter, Anna Lasorella, Kristin R. Swanson, Michele Ceccarelli, Antonio Iavarone, Nhan L. Tran. Multiregional sampling of high grade glioma identifies regional biologic signatures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1507.

Abstract Patients with glioblastoma (GBM) face poor outcomes; the 5-year survival rate is 7% with standard of care treatments, which are frequently associated with systemic toxicity. Tumor Treating Fields (TTFields) are electric fields that disrupt critical cancer cell processes. The TTFields therapy device consists of a portable electric field generator and arrays placed on the patient’s scalp, thus delivery is locoregional and noninvasive. Currently, TTFields therapy is approved for recurrent and newly diagnosed GBM, based on the phase 3 EF-11 (TTFields 200 kHz) and EF-14 studies (TTFields therapy 200 kHz + temozolomide), respectively. These studies confirmed that TTFields therapy had a tolerable safety profile with mild-to-moderate localized skin adverse events (AEs) being the most common related AEs. Here, we present an updated analysis of the largest global real-world evidence dataset of patients with brain tumors receiving TTFields therapy over an 11-year time period. Unsolicited safety data were obtained from routine post-marketing activities, including published literature and interactions with patients, caregivers, and healthcare professionals. Safety data were grouped according to age, diagnosis, and sex. AEs were categorized using MedDRA version 25. Data from 25,898 patients were included in this analysis; median age was 59 years (range: 3-103) for patients with known age. Diagnoses were ndGBM (67.7%), rGBM (26.1%), anaplastic astrocytoma/oligodendroglioma (4.2%) and other (2.1%). Most (n=17,817, 68.8%) patients were 18-65 years of age; n=93 (0.4%) were pediatric/adolescent patients (&lt;18 years), and n=7,808 (30.2%) were elderly patients (&gt;65 years). For 130 patients (0.5%) age was not known. Two-thirds of patients were male, which reflects the preponderance of CNS tumors in males. Most patients were based in North America (72.1%), followed by Europe, the Middle East and Africa (23.3%), and Japan (4.6%). Overall, 72.4% of patients experienced at least one AE, with 55.9% being related to TTFields therapy. The most common AEs (overall and related to TTFields therapy) were skin reactions (42.0%), electric (tingling) sensations (13.5%), and heat (warmth) sensations (11.8%). The percentage of patients experiencing ≥1 AE in the pediatric/adolescent, 18-65, and elderly groups was 63.4%, 74.6%, and 68.4%, respectively. The percentage of females and males experiencing ≥1 AE was 75.2% and 70.9%, respectively. These long-term, real-world data from the largest global dataset of patients with brain tumors using TTFields therapy to date demonstrate a tolerable safety profile consistent with pivotal clinical studies. There were no new safety signals, and most AEs were manageable localized mild-moderate skin events that can be resolved. The distribution of AEs between age and sex was similar, with broad applicability among different patient groups. Citation Format: Maciej M. Mrugala, Wenyin Shi, Fabio Iwamoto, Rimas V. Lukas, Joshua D. Palmer, John H. Suh, Martin Glas. Patients with glioblastoma (GBM) treated with tumor treating fields (TTFields) therapy: post-marketing safety data over the last decade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3221.