Access Program Research Articles

Screening and Telephone-Based Intervention for Unhealthy Alcohol Use in a Diverse Federally Qualified Health Center System in Texas.

Screening and brief intervention (BI) can reduce risky alcohol use but has not been widely implemented in primary care settings. We sought to implement a screening and telephone-based program within a Federally Qualified Health Center (FQHC). Prior to this program, adult patients were routinely screened using AUDIT-C with no further systematic follow-up. We designed a team-based, tele-care-centered program to (1) follow-up positive screening results or provider referrals with full AUDIT and (2) provide a social worker-administered two-session BI for patients with AUDIT 4-12; those with high AUDIT scores received BI and were offered pharmacotherapy and/or referral for additional support. Repeat AUDIT was administered at 3-6months. From March 2021 to May 2023, 3959 patients were screened using AUDIT-C, with 632 (16%) screening positive. Mean age was 44; 47% identified as female, 58% as Hispanic/Latino; 43% received care through the county-based Medical Access Program (MAP). Men, those with commercial insurance, and English-speakers were more likely to screen positive. Using telephone outreach to direct referrals and to those screening positive, trained counselors successfully administered the full AUDIT to 412 participants. Initial AUDIT scores were ≤ 12 (n = 281, 68.2%) and > 12 (n = 131, 31.8%). Among patients who completed the initial AUDIT, mean age was 46; 32% identified as female, 86% as Hispanic/Latino, and 66% were insured through MAP. Of the 412, 400 (97%) completed one counseling session and 297 (72%) completed two. Of the 131 with initial AUDIT > 12, 19 received pharmacotherapy and 13 had one or more visits with our addiction medicine service. For the 251 patients with AUDIT data at 3-6months, the mean score change was - 4.1 (95% CI - 3.4, - 4.7). Spanish-speaking patients showed larger decreases than English-speakers; there were no other statistically significant differences. Screening and telephone-based BI reduces unhealthy alcohol use in diverse adult FQHC patients.

"Real-life" Data of Zanubrutinib in Patients with Waldenström Macroglobulinemia - A Multi-Center Retrospective Study.

Waldenström macroglobulinemia (WM) is a rare indolent lymphoma. Zanubrutinib (ZAN), a second-generation BTK inhibitor, has been approved for the treatment of WM in any line of therapy in 2021. Between November 2020 and January 2022, an expanded access program of ZAN opened in Israel for the treatment of patients with relapsed refractory (RR)-WM or those ineligible for chemotherapy or ibrutinib in first line. This is a multi-center retrospective study aiming to provide real-world data on ZAN in patients with WM in Israel. Demographic and clinical data were collected and coded from electronic files. Response was evaluated by the investigator's assessment. As the program closed, patients transitioned to commercial ZAN. 13 patients (12 RR; 1 treatment-naive) were enrolled across 8 centers in Israel. The median age at ZAN initiation was 71 years (range, 50-85); 6 were males; 10 had high IPSS-WM. RR pts had a median of 1 (1-4) prior lines of therapy. Other than progressive disease after chemoimmunotherapy (CIT), the most common considerations for choosing ZAN were patients' age and/or comorbidities (n=5), as well as ibrutinib toxicity. The initial ZAN dose was reduced in 4 pts. The median time on ZAN was 19.5 months (2.9-29.5). Of 12 evaluable patients, the ORR was 83% with 3 minor responses, 6 PR, and 1 VGPR. With a median follow-up of 19.6 months, 7 patients were still on ZAN, 5 progressed, 4 while on ZAN, and 1 after ZAN was stopped due to AE. 18 months PFS and OS were 60.5% and 77%, respectively. Eight (61%) patients had AEs of any grade, and 3 (23%) of grade 3-4; 2 stopped ZAN due to congestive heart failure and extreme fatigue. The results of this real-world high-risk population are consistent with prospective studies highlighting the efficacy and safety of ZAN.

Reprocessing of eXpendable BathyThermograph (XBT) profiles from the Ligurian and Tyrrhenian seas over the time period 1999–2019 with a full metadata upgrade

Abstract. The advent of open science and the United Nations Decade of Ocean Science for Sustainable Development are revolutionizing the ocean-data-sharing landscape for an efficient and transparent ocean information and knowledge generation. This blue revolution raised awareness on the importance of metadata and community standards to activate interoperability of the digital assets (data and services) and guarantee that data-driven science preserves provenance, lineage and quality information for its replicability. Historical data are frequently not compliant with these criteria, lacking metadata information that was not retained, crucial at the time of data generation and further ingestion into marine data infrastructures. The present data review is an example attempt to fill this gap through a thorough data reprocessing starting from the original raw data and operational log sheets. The data gathered using XBT (eXpendable BathyThermograph) probes during several monitoring activities in the Tyrrhenian and Ligurian seas between 1999 and 2019 have first been formatted and standardized according to the latest community best practices and all available metadata have been inserted, including calibration information never applied, uncertainty specification and bias correction from Cheng et al. (2014). Secondly, a new automatic quality control (QC) procedure has been developed and a new interpolation scheme applied. The reprocessed (REP) dataset has been compared to the data version, presently available from the SeaDataNet (SDN) data access portal, processed according to the pioneering work of Manzella et al. (2003) conducted in the framework of the European Union Mediterranean Forecasting System Pilot Project (Pinardi et al., 2003). The comparison between REP and SDN datasets has the objective to highlight the main differences derived from the new data processing process. The maximum discrepancy among the REP and SDN data versions always resides within the surface layer (REP profiles are warmer than SDN ones) until 150 m depth generally when the thermocline settles (from June to November). The overall bias and root mean square difference are equal to 0.002 and 0.041 °C, respectively. Such differences are mainly due to the new interpolation technique (Barker and McDougall, 2020) and the application of the calibration correction in the REP dataset. The REP dataset (Reseghetti et al., 2024; https://doi.org/10.13127/rep_xbt_1999_2019.2) is available and accessible through the INGV (Istituto Nazionale di Geofisica e Vulcanologia, Bologna) ERDDAP (Environmental Research Division's Data Access Program) server, which allows for machine-to-machine data access in compliance with the FAIR (findable, accessible, interoperable and reusable) principles (Wilkinson et al., 2016).

Research, Access, and Digitisation: Reflections on Responsible Stewardship in the Online Era

This article reflects on the impact of digitisation programs for researcher access to archival materials. Using the author’s experience as both a researcher using digitised material and as a manager of archival programs, the article considers the opportunities and challenges of researcher demand for digital access and suggests the archival value of responsible stewardship is a useful concept when navigating access in the online era.

Reimagining professional development for school leaders in Brazil, Chile, and Colombia: an examination of current approaches and future directions

ABSTRACT This study examines current approaches to professional development (PD) for school leaders in Brazil, Chile, and Colombia. While PD programs indicate significant progress, school leadership remains in an early stage of development. The findings highlight the need for national policy commitments to ensure long-term sustainability. The challenge is not only in offering accessible programs for new principals but also in ensuring quality and promoting continuous professionalisation. The analysis underscores the need for individual-centred PD approaches that prioritise the personal growth of school leaders, recognising the multifaceted dimensions of their roles. Additionally, it emphasises the importance of embedding professional development within a learning system that fosters partnerships between academia, government, and wider society. Addressing the need for a more context-sensitive approach to professional preparation, the study also highlights the political dimension of school leadership, advocating for programs that equip leaders with the political awareness necessary to navigate complex policy contexts effectively. Recognising the influence of the Global North, this study advocates for reimagining PD approaches to integrate and prioritise contextualised practices and knowledge, considering the diverse realities and challenges faced by educators in the region.

An Easily Accessible, Semi-Automated Approach to Creating Personalized Normative Feedback and Risk Feedback Graphics.

Personalized normative feedback interventions show efficacy in reducing health risk behaviors (e.g., alcohol use, sexual aggression). However, complex personalized normative feedback interventions may require manual methods of inputting participant data into graphics, which introduces error, and automated approaches require substantial technical costs and funding and may limit the types of feedback that can be provided. To make personalized normative feedback more accessible, we outline a method of using easily accessible software programs including IBM Statistical Package for the Social Sciences (SPSS), Microsoft Excel, and Microsoft PowerPoint, to create and display complex personalized normative feedback graphics. We also describe methods through which personalized normative feedback graphics can be created within a larger preventive intervention for alcohol and sexual assault in college men. We first provide step-by-step instructions for collecting data and then creating semi-automated syntax files within SPSS and Excel to merge participant data into complex personalized normative feedback graphics in Excel. To do so, we append annotated syntax in text and in supplemental material. Next, we outline the process of creating risk feedback graphics, whereby individual items or exact wording of items are displayed back to the participant. Finally, we provide guidance regarding the process of translating graphics from Excel for viewing via PowerPoint without having to manually update PowerPoint slides for each presentation. Via the described syntax and graphic generation, researchers are then able to create semi-automated personalized normative feedback and risk feedback graphics. This tutorial may help in increasing the dissemination of complex personalized normative feedback interventions.

Teclistamab in relapsed refractory multiple myeloma: a multi-institutional real-world study from the French early access program.

Not available.

Bridging the gap: The role of geographic proximity in enhancing seed sustainability in Bandung District

Abstract Climate change poses mounting challenges to agriculture in the Bandung District, Indonesia, and across the Global South. Seeds are the foundation of resilient food systems, and sustainable seed systems are essential for adaptation. This study offers a unique, holistic investigation of seed sustainability within the Bandung District. Utilizing multidimensional scaling and an independent t-test on a surveyed sample of 100 farmers across 8 villages, we analyze the interwoven social, economic, ecological, institutional, and technological dimensions shaping seed sustainability within the region. A core finding reveals the impact of geographic proximity to the government center on economic sustainability within the seed systems. Further, this analysis demonstrates the importance of policies promoting decentralized agricultural support, enhanced seed-saving infrastructure, and accessible farmer education programs to promote farmer agency, food security, and district-wide agricultural resilience. Findings transcend the context of Bandung, informing sustainable seed development practices in both regional and global contexts.

Multi-Prong Formative Evaluation of a Pediatric Clinical-Community Food Access and Nutrition Education Intervention.

To understand pediatricians', community partners', and food insecure parent/caregivers' perspectives on addressing food access and nutrition education in clinical settings, and to conduct a formative evaluation of a clinical-community food access and nutrition education intervention. A mixed-methods evaluation. Data was collected from pediatricians and parents/caregivers recruited from one urban pediatric primary care clinic, and from community partners involved in food access. Pediatricians (n = 14), parents at risk of food insecurity (n = 7), and community partner staff (n = 8) participated in qualitative interviews. A cross-sectional survey among pediatricians assessing demographics, nutrition training, and knowledge of food access programs was administered. Semi-structured virtual interviews were conducted to understand experiences with food insecurity and food access programs, and to identify content and delivery preferences for a clinical-community intervention. Descriptive statistics were used to characterize the pediatrician and parent demographics and pediatrician nutrition knowledge. A hybrid deductive-inductive thematic analysis was used to identify emerging themes from qualitative interviews. Few pediatricians (n = 3, 11%) reported receiving previous nutrition training, and knowledge-based food access program questions revealed significant gaps in pediatricians' understanding of program eligibility. Thematic analyses underscore challenges in addressing food insecurity in the clinical setting, gaps in clinical-community partnerships, and barriers to participating in food access programs. Findings provide recommendations for the development of clinical-community food access and nutrition education interventions.

Real‐world impact of pembrolizumab availability for deficient mismatch repair metastatic colorectal cancer

AbstractBackgroundImmunotherapy has emerged as a standard treatment for deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC). Pembrolizumab became widely available as a first‐line (1L) option in Australia following the Pharmaceutical Benefits Scheme (PBS) listing in August 2021. The uptake of new treatment options can be lengthy.MethodsThe Treatment of Recurrent and Advanced Colorectal Cancer mCRC registry data at participating Australian sites was analysed from January 2015 (when MMR testing became routine). 1L treatment of dMMR cancers was compared with pre‐ and post‐PBS funding.ResultsOut of 2819 patients, 2344 (83%) had known MMR status. Of these, 162 (7%) were dMMR, which was associated with older age (median age 69 vs 63 years, P = 0.001), a right‐side primary (68% vs 31%, P < 0.001) and a BRAF V600E mutation (49% vs 11%, P < 0.001). Prior to August 2021, 85 out of 117 (73%) patients with dMMR received 1L treatment: 63 out of 85 (74%) chemotherapy and 20 out of 85 (24%) immunotherapy. Following approval, 39 out of 45 (87%) received 1L treatment and 39 out of 39 (100%) pembrolizumab. Of the patients 75 years and older, a significantly higher proportion of patients were treated with any 1L therapy post‐PBS listing (89% vs 60%, P = 0.036).ConclusionPreviously reported associations of dMMR were observed. The higher‐than‐expected proportion of patients with dMMR is likely driven by the inclusion of older patients in this real‐world study. Many patients were able to access immunotherapy prior to PBS listing, potentially through trials or access programs. Early uptake of pembrolizumab following PBS listing has been high, and this effective and well‐tolerated option has increased the proportion of elderly patients receiving active therapy.

Real-world safety of spesolimab in generalized pustular psoriasis: Evidence from an expanded access program in Argentina

Introduction: Generalized pustular psoriasis (GPP) is a heterogeneous, systemic, neutrophilic, inflammatory disease associated with chronic symptoms and periods of flaring. Spesolimab is an anti-interleukin-36 receptor monoclonal antibody approved for the treatment of flares in adult patients with GPP in Argentina (17 Aug 2023).1 Here, we present safety data from a real-world expanded access program (EAP: 22 Feb 2023–10 Jan 2024) in Argentina which provided early access to spesolimab intravenous (IV) for GPP patients presenting with a flare with no other treatment options. Methods: Patients (18–75 years old) diagnosed with GPP received a 900mg dose of spesolimab IV for flare treatment, with an optional second dose after 1 week for persistent flare symptoms. Adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were recorded for up to 16 weeks after the last spesolimab infusion.Results: Six female patients were treated with spesolimab IV (1 dose, n=2; 2 doses, n=4).Mean (standard deviation [SD]) age: 49.3 (11.5) years (range: 30–60 years), mean (SD) body mass index: 28.1 (5.8) kg/m2, and mean (SD) follow-up: 3.85 (0.11) months. At baseline, GPP had been diagnosed within ≤1 year (n=2), >1–≤5 years (n=1), and >10 years (n=3). Reported flare triggers were stress (n=2), treatment withdrawal (n=1), heat (n=1), lack of current treatment efficacy (n=1), and unknown (n=1). At baseline, 4 patients had ≥1 comorbidity, including hypertension (n=2), tachycardia, hypothyroidism, chronic gastritis, arthritis, and epilepsy (each n=1). Five patients reported use of ≥1 concomitant medication (including immunosuppressants and corticosteroids) during the EAP; 1 patient had discontinued ustekinumab (biologic). Three patients had signs of plaque psoriasis within the past year and had received treatment for plaque psoriasis; 1 patient had ongoing plaque psoriasis. In total, 4 patients had any AEs (all 4 patients had mild AEs [influenza, catarrh, pruritis, rash, pain] and 1 of these patients also had a moderate AE [headache]). Two drug-related AEs (pruritus and rash) were reported in 1 patient. The hypersensitivity event (rash) was non-serious. There were no reports of SAEs, AESIs, or AEs that led to discontinuation/death. Conclusion: Spesolimab showed a favorable safety profile in patients with GPP, including patients with comorbidities and those taking concomitant medication. Findings were comparable with a Phase 2a randomized controlled trial in patients with GPP flares (EFFISAYIL 1).

Refugee Caregivers' Perceptions of Using Mindfulness-Based Interventions to Support Coping Skills in Children with Disability in Jordan.

Background: Refugee children with disabilities are vulnerable to developing dysfunctional coping skills due to barriers in accessing health care services, including occupational therapy (OT). This study investigated the perceptions of refugee caregivers regarding the use of mindfulness-based interventions (MBIs) as a treatment for coping skills among their children with disabilities. Methods: A qualitative survey was used to analyse the coping mechanisms and access to services among refugee children with disabilities, as well as their caregivers' perceptions regarding the use of MBIs. The caregivers were recruited using convenience sampling from a database of individuals at the Al-Baqa'a refugee camp in Jordan via their community-based rehabilitation (CBR) centre. A demographic survey was sent to 156 refugees using WhatsApp. Refugees above the age of 18 years identifying as the caregivers of children with disabilities were eligible. Twenty-eight individuals completed the survey, and twenty-six were eligible. Open-ended questions asked about their child's struggles, supports, barriers to support, and perceptions of MBIs. The data were collected via Google Sheets. Three researchers coded the responses using a descriptive coding method and line-by-line analysis. Results: Five themes were derived from the responses: "Daily Challenges", "Support and Strategies", "barriers to accessing support", "MBIs: Caregiver Perceptions", and "MBIs: Barriers". The participants identified the behavioural, emotional, and cognitive challenges impacting their child's participation. Financial and environmental constraints, stigma, and timing were the reported barriers to services. The participants felt positive about the potential of MBIs to support their children. Conclusions: Overall, this study obtained foundational data to establish accessible mental health programmes for refugees with disabilities. Further research is needed to transcend the barriers and maintain MBI programmes in the community and the home settings.

Audio description for all? The benefits and concerns of extending access provision to sighted people

AbstractAudio description (AD) is an established part of museums' access programs for blind and partially blind (BPB) people. This paper explores the merits and caveats regarding “AD for all”, rolling out the provision for sighted people as well. It draws from four separate Access All Senses (AAS) events in three different London museums, each conducted under slightly different conditions. In addition to collecting nearly 100 audience feedback forms, this study has involved museum access staff, audio describers, and BPB art lovers. These events demonstrate that there is a demand among sighted people to include AD in museum tours as “guided looking”. The main concern regards the unintended consequences that could threaten the specific provision that BPB people need. A brief survey at the end offers examples of museum initiatives where AD is being rolled out while protecting these interests.

Assessing the Adoption and Utilization of Drip Irrigation Technology among Tapioca Farmers in Thuraiyur Taluk, Tiruchirappalli District, Tamil Nadu, India

Aims: The study examines the adoption and utilization of drip irrigation technology among tapioca farmers in Thuraiyur taluk, Tiruchirappalli district, Tamil Nadu. Study Design: An ex-post-facto research design is used to collect data from 90 farmers across four villages. Place and Duration of Study: Thuraiyur taluk, Tiruchirappalli district, Tamil Nadu. The study has been conducted for a period of six months (April – September, 2024) Methodology: Out of the district’s eleven taluks, Thuraiyur had the highest number of tapioca farmers, making it ideal for this study. Four villages—Naganallur, Settikadu, Sobanapuram and Koppampatti—were chosen from Thuraiyur taluk for their significant tapioca cultivation and large farmer populations. A stratified random sampling method is used to select participants. The primary data are collected through structured questionnaires and personal interviews with farmers. Secondary data are obtained from relevant literature, reports and government records. The dependent variables are the adoption level of drip irrigation and the extent to which the farmers use the drip irrigation technology. Descriptive statistics mean, percentage and frequency distribution are used in the study. Results: Findings reveal that the majority of farmers (82.22%) demonstrated medium to high adoption of drip irrigation technology. Key practices like checking the workability of the foot valve and maintaining pipeline fittings are widely adopted, while more advanced techniques such as fertigation showed lower adoption levels. Drip irrigation was used universally for water management, with 87.80% of farmers acknowledging its role in reducing water usage and 83.30% citing reduced labor needs. Conclusion: However, only 46.70% of respondents reported increased yields, indicating potential gaps in system optimization. The study suggests the need for greater technical training, financial assistance and improved extension services to enhance the adoption of advanced drip irrigation practices. Policy measures, such as increased awareness of government schemes like PMKSY and accessible training programs, are recommended to maximize the benefits of drip irrigation in improving water efficiency, crop yield and sustainable farming practices.

EPCO-49. SEX-SPECIFIC CHROMATIN REMODELING DRIVES TUMORIGENESIS IN GLIOBLASTOMA

Abstract Glioblastoma (GBM) is the most prevalent primary malignant brain cancer and has higher incidence and lower survival in males compared to females. The SWI/SNF chromatin remodeling complexes, including canonical BAF (cBAF), polybromo-associated BAF (PBAF), and non-canonical BAF (ncBAF), play a critical role in multiple cancers including gliomas. However, their role in gliomagenesis and progression remains largely unknown. We analyzed 18 human glioma specimens for BAF complex mRNA expression by CNS WHO grade and used these data to guide CRISPRi knockdown of BAF components in syngeneic murine male and female GBM astrocytes. BAF complex knockdown revealed marked sex-specific differences in proliferation. Specifically, Smarce1 or Smarcb1 knockdown (cBAF & PBAF) resulted in increased growth in male astrocytes but decreased growth in females. Brd7 (PBAF) knockdown enhanced growth in both sexes, while Brd9 (ncBAF) had minimal impact. We utilized extreme limiting dilution analysis (ELDA) to assess the clonogenic potential of GBM cells with depleted BAF components. Notably, cells with BRD7 knockdown displayed enhanced sphere-forming capacity in both male and female cells. Male cells with Smarce1or Smarcb1 knockdown showed increased clonogenic frequency, whereas females with Smarce1 knockdown had a marked reduction in sphere formation. Brd9 knockdown did not affect the sphere-forming capacity in male or female cells, in part due to compensatory plasticity of an alternate BAF complex. Epitranscriptomic analysis is ongoing and demonstrates sex-specific differences in chromatin accessibility and downstream gene expression programs based on BAF complex knockdown. Immunoprecipitation coupled with mass spectrometry was performed to elucidate the structure and assembly of the BAF complex in GBM cells. Understanding sex-specific mechanisms of BAF chromatin remodeling complex in glioma pathogenesis may yield critical insights for the development of precision therapeutics that have the potential to improve patient outcomes.

CTNI-66. IDH-MUTANT GLIOMA PATIENTS TREATED WITH VORASIDENIB: ONGOING DATA FROM THE VORASIDENIB EXPANDED ACCESS PROGRAM

Abstract BACKGROUND Vorasidenib (VOR) is an oral, brain-penetrant dual inhibitor of mutant isocitrate dehydrogenase 1/2 (mIDH1/2) demonstrating clinical efficacy and safety in patients with mIDH1/2 glioma in the phase 3 INDIGO study (NCT04164901). Servier launched an expanded access program (EAP, NCT05592743) in November 2022 designed to provide access to VOR for patients with mIDH1/2 glioma. Early clinical outcomes of patients treated in this EAP are presented. METHODS Eligible participants were aged ≥12 years with mIDH1/2 glioma and, in the opinion of the treating oncologist, would potentially benefit from treatment with VOR. Safety assessments occur every two weeks for the first two 28-day cycles, then monthly for the duration of treatment. RESULTS As of the March 31, 2024 data cutoff, 71 participants have initiated treatment with VOR. Mean (SD) age was 42.7 (14.8) years; 39 (55%) were male; and 34 (48%) with astrocytoma. mIDH mutation status was 46 (65%) mIDH1. One participant had separate tumors with either mIDH1 or mIDH2 identified. The majority of participants had grade 2 gliomas (n=51 [72%]) and non-contrast–enhancing disease (n=49 [69%]). As of the data cutoff, 62 (87%) participants remain on treatment, with the majority initiating treatment within the past 6 months (n=49 [69%]). Nine (13%) participants have discontinued treatment due to: radiographic progressive disease (n=3); clinical progressive disease (n=4); adverse event (AE) unrelated to treatment (n=1); or other reason (n=1). Three participants have died (disease progression [n=2], unrelated infection [n=1]). At least one AE of any grade was seen in 35 (49%) participants, with 4 (6%) experiencing unrelated serious AEs. Eight (11%) patients had AEs of special interest (defined as grade 2 or higher ALT/AST elevations). Ten (14%) patients had AEs that led to dose interruption and one (1%) patient had dose reduction. Additional treatment duration and various subgroup analyses will be presented.

CTNI-27. SYSTEMIC DELIVERY OF LOW ENERGY RADIOFREQUENCY ELECTROMAGNETIC FIELDS FOR THE TREATMENT OF PATIENTS WITH PRIMARY BRAIN TUMORS

Abstract BACKGROUND Tumor Treating Fields plus maintenance temozolomide (mTMZ) showed a survival advantage in the first-line glioblastoma (GBM) treatment. The survival benefit remains limited in patients with unmethylated MGMT gene promoter. The AutEMsys device emits low-energy amplitude modulated systemic electromagnetic fields (EMF) at patient specific frequencies. It is an outpatient procedure that can be integrated with mTMZ. METHODS This study involved a prospective compassionate access program targeting adult GBM patients using an intrabuccal EMF exposure via AutEMsys in addition to chemoRT+mTMZ. The program explored the effects on survival and patients’ reported quality-of-life (QOL) by EORTC-QL-C30. Patients underwent a 90-minute session of EMF exposure therapy repeated every 2 weeks until progression, deterioration in QOL or death. All patients had pathological specimens for diagnosis, IDH mutation status through NGS techniques, and MGMT promoter region methylation status. RESULTS 31 participants were enrolled, including 29 with GBM and 2 with diffuse midline glioma. 14 patients (45%) received EMF+chemoRT followed by EMF+mTMZ and 17 patients (55%) received EMF+mTMZ (post chemoRT). Survival time was measured from the start of mTMZ to the date of the last follow-up. The median overall survival (mOS) for all 31 patients was 26.0 months (95% CI: 14.4 – 37.2 months). Specifically for 21 patients with unmethylated MGMT, the mOS was 25.0 months (95% CI: 15.9 – 34.1 months). Similarly, for the 28 patients with IDH wildtype status, the mOS remained 26.0 months (95% CI: 9.6 – 42.4 months). The addition of AutEMsys with chemoRT+mTMZ demonstrated an improved role functioning in 79% of patients with 25% of these with >10-point score. CONCLUSION The AutEMsys device has shown promising initial results when added to chemoRT+mTMZ treatment of GBM. These findings warrant further prospective investigation and validation in a multicenter clinical trial setting.

CTNI-72. VAL-083 IN PATIENTS WITH RECURRENT GLIOBLASTOMA TREATED UNDER EXPANDED ACCESS PROGRAM

Abstract BACKGROUND Current standard-of-care for glioblastoma (GBM) includes surgery followed by chemoradiation with temozolomide (TMZ) followed by adjuvant TMZ. Almost all GBM patients experience disease progression despite upfront standard-of-care treatment, with a median overall survival of 3-9 months after first recurrence. There are limited treatment options at the time of disease progression, apart from participation in clinical trials. VAL-083 is a bi-functional DNA damaging agent that induces inter-strand DNA cross-links at N7-guanine in a manner independent of O6-methylguanine-DNA-methyltransferase (MGMT). METHODS Under an Expanded Access program (NCT03138629), we used VAL-083 to treat 30 patients with recurrent GBM who were not eligible to participate in clinical trials. Here we report safety and efficacy results. RESULTS Four patients (13.3%) with leptomeningeal disease were excluded from efficacy evaluation. All patients received chemoradiation with TMZ. Twelve (12/26; 46.2%) patients had ≥2 recurrences and 9/26 (34.6%) had prior lomustine. All tumors had ≥1 mutation, with 14/26 (53.8%) having ≥5 mutations; one patient had a hypermutator phenotype. The most common mutations were TERT (57.7%), PTEN (38.5%), TP53 (26.9%), and NF1 (26.9%). All patients started treatment with VAL-083 at 30 mg/m2/day administered on 3 consecutive days every 21 days. Eight (8/26; 30.8%) patients received bevacizumab concurrently with VAL-083. Eight (8/26; 30.8%) patients had a VAL-083 dose reduction. Patients received a median of 3.0 (5-95pth 1-10) VAL-083 treatment cycles. Median progression free survival (mPFS) and median overall survival (mOS) from last disease progression was 5.1 (95%CI: 2.7-7.2) and 9.8 (95%CI: 5.3-16.4) months, respectively. VAL-083 was well-tolerated and the most frequent adverse events were consistent with prior experience, i.e., thrombocytopenia and neutropenia. CONCLUSIONS Use of VAL-083 continues to show benefit in the treatment of GBM patients who have had multiple recurrences and have limited therapeutic options.

NCOG-07. SAFETY OF ONC201 TREATMENT IN PATIENTS WITH PREVIOUSLY TREATED H3 K27M-MUTANT GLIOMA: RESULTS FROM ONC028, AN ONGOING COMPASSIONATE USE PROGRAM

Abstract PURPOSE H3 K27M-mutant diffuse midline glioma (DMG) has a poor prognosis, with a median overall survival of 1 year and no proven treatments beyond radiotherapy. ONC201 (dordaviprone), a first-in-class imipridone, previously demonstrated durable responses in patients with recurrent H3 K27M-mutant DMG. The present analysis reports safety data from ONC028, a compassionate use program (CUP) for patients with previously treated H3 K27M-mutant glioma. METHODS ONC028 is an expanded access program that provides ONC201 monotherapy to patients with H3 K27M-mutant glioma. Eligible patients are adults or pediatric patients with H3 K27M-mutant glioma, prior therapy including at least radiation, and adequate organ function. Patients must be ineligible for enrollment in other ongoing clinical studies evaluating ONC201. ONC201 is administered orally once weekly at 625 mg or dose-equivalent based on body weight for pediatric patients. MRIs are performed every two 28-day cycles for the initial 12 months, thereafter every 2-3 cycles. Treatment continues until disease progression, unacceptable adverse events (AEs), or withdrawal of consent. Treatment may continue post-progression at the discretion of the treating physician. Bevacizumab use for radiation necrosis or symptom management is acceptable. AEs are assessed by NCI CTCAE v5.0 criteria. RESULTS The 422 enrolled patients include 191 adults (45.2%) and 231 children (54.7%); 87.1% had a performance score ≥60 and the most common tumor location was the pons (57.3%). Any-causality Grade ≥3 AEs have been reported in 200 patients (47.4%). Grade ≥3 treatment-related AEs (TR-AEs) were reported in 19 (4.5%) patients; the commonest was decreased lymphocyte count, occurring in 3 (0.7%) patients. Any-causality serious AEs (SAE) were reported in 43.1% (n=182) patients. There were 10 (2.4%) patients with reports of treatment-related SAEs, the commonest were ascites, nausea, vomiting, and seizure, each occurring in 2 patients (0.2%). CONCLUSIONS ONC028 provides expanded access to ONC201 treatment for patients with previously treated H3 K27M-mutant glioma who are ineligible for enrollment in ongoing trials of ONC201. ONC201 treatment remains well-tolerated.

CTNI-71. RELA FUSION-POSITIVE EPENDYMOMA, DIFFUSE MIDLINE GLIOMA AND GRADE 4 IDH MUTANT ASTROCYTOMA TREATED WITH VAL-083 UNDER EXPANDED ACCESS: CASE REPORTS

Abstract RELA fusion-positive ependymoma is associated with supratentorial location, higher WHO grade and poor prognosis. Diffuse Midline Glioma (DMG) is a relatively rare CNS tumor, originating in the midline location of the brain. Surgical intervention is restricted to biopsy and radiation. Grade-4 astrocytoma, is highly aggressive with rapid progression. Standard treatment includes surgery and radiation therapy, with limited systemic options other than clinical trials for recurrent disease. VAL-083 is a DNA-targeting agent which rapidly induces inter-strand DNA cross-links at O6- and N7-guanine inducing double-strand breaks causing cell death and acts independent of MGMT DNA repair in high-grade gliomas. We report on 4 patients who had recent disease progression and unmethylated MGMT promoter status treated with VAL-083 under an expanded access program: Case #1: a 47-yo male diagnosed with IDHwt, RELA fusion-positive ependymoma. Case #2: an 18-yo male diagnosed with IDHwt, MAP2K1 and RELA fusion-positive ependymoma. Case #3: a 25-yo male diagnosed with IDHmut Grade 4 astrocytoma, with ATRX, INPP4A, RET and TP53 mutations. Case #4: a 21 yo male diagnosed with IDHwt DMG of the brain stem. All patients had multiple recurrences, received radiation and multiple systemic treatment regimens. They received VAL-083 (30 mg/m2 for 3 days every 21 days) under an expanded access program. Patients with ependymoma received 6 and 5 cycles of VAL-083, (case 1 and 2, respectively), while the patients with IDHmut Gr 4. astrocytoma and DMG received 5 and 18 cycles of VAL-083, respectively. No adverse events were reported and no dose reductions were required. These cases highlight that VAL-83 may be a treatment option for recurrent RELA fusion-positive ependymoma, Gr4. IDHmut astrocytoma, and DMG refractory to other treatment regimens. Additional outcomes related to these cases will be presented at the meeting. Clinicaltrials.gov Identifier: NCT03138629. The treatment plans for the EA patients were approved by MD Anderson Cancer Center IRB