bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTIM-12. A RETROLECTIVE ANALYSIS ON THE SAFETY, EFFICACY AND IMMUNOGENICITY OF 203 GLIOBLASTOMA PATIENTS TREATED WITH PERSONALIZED THERAPEUTIC CANCER VACCINES (PTCV)
Authors: Latzer Pauline , Zelba Henning , Battke Florian , Bartsch Oliver , Reinhardt Annekathrin , Pertuch Eike , Shao Borong , Rabsteyn Armin , Okech Thomas , Golf Alexander , Kyzirakos-Feger Christina , Kayser Simone , Feldhahn Magdalena , Wünsche Julian , Hadaschik Dirk , Götte Dieter , Biskup Saskia 
Published: November 2024

Abstract

BACKGROUND
Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor. Despite of the current SoC, patients have a poor prognosis with a median OS of about 14-17 months.Method,

RESULTS
We report retrospectively analyzed data from 203 GBM patients (IDH wildtype) who added PTCV derived from patient individual tumor mutations to their treatment regimen in the setting of individual treatment attempts (ITA) in Germany. Data were analyzed re. vaccine induced T cell responses and safety acc. to CTCAE terminology version 5.0. Subsets of patients with and without hypermethylation of the MGMT promoter were further evaluated re. efficacy. Treated patients had a median age of 53 years at diagnosis, started vaccination after a median of 11 months after diagnosis, received a median of 8 immunizations with a median of 20 neoepitope peptides, and had a median follow-up time since first vaccination of 21 months. They usually received SoC (Stupp scheme), often accompanied by additional therapies. In general, the PTCV was well tolerated, and most patients experienced only Grade 1 and 2 AEs. Most frequently injection site reactions were observed (67%). Seven patients developed Grade 3 allergic or anaphylactic reactions after 7 or more vaccinations. For 119 patients T-cell responses against the vaccinated neoepitopes were investigated. Almost all patients developed vaccine induced T-cell responses (97%). 71% of patients showed both CD4+ and CD8+ T-cell responses towards vaccinated peptides. Immune responses usually increased over time peaking within 3-6 months. Median OS of the whole cohort was 26 mo (95% CI 24, 31). Primary GBM patients without recurrence events before the start of vaccination and with or without hypermethylated MGMT promoter status showed a mOS of 41 months (95% CI: 32, NA) or 23 months (95% CI: 20, NA), respectively.

CONCLUSION
The retrospective data analysis from a real-world cohort of GBM patients suggests that PTCV are safe, immunogenic, and may prolong the survival of patients.
CTIM-14. EARLY SAFETY DATA FROM A RANDOMIZED, MULTICENTER, DOUBLE-BLIND, PHASE 2B STUDY OF IGV-001, AN AUTOLOGOUS CELL IMMUNOTHERAPY, VERSUS PLACEBO, IN NEWLY DIAGNOSED GLIOBLASTOMA (NDGBM)
Authors: Bradley Elder J , Hanft Simon , Lee Ian Y , Farrell Christopher , Boockvar John A , Zacharia Brad E , Kim Lyndon , Schulder Michael , Correia Carlos Eduardo Silva , Ramakrishna Rohan , Wong Eric T , Wu Julian , Agarwal Vijay , Amankulor Nduka , Bhatia Ankush , Evans Linton T , Brennan Cameron , Gill Brian J , Sengupta Soma , Quiñones-Hinojosa Alfredo , Giglio Pierre , Wu Kyle , Wu Synphen H , Falo Cristina , Walbert Tobias , Robin Adam , Alnahhas Iyad , Vojnic Morana , Wernicke A Gabriella , Aregawi Dawit , Maurer Robert , Ghatan Saadi , Singer Samuel , Jeyapalan Suriya , Magge Rajiv , Malik Athar N , Patel Nitesh , Chan Amy , Iwamoto Fabio , Hormigo Adilia , Higgins Dominique , Dey Mahua , Moss Nelson S , Sherman Wendy , Neese Leila , Pennock Gregory K , Scott Charles , Perez-Olle Raul , Andrews David W 
Published: November 2024

Abstract
Standard of care (SOC) for ndGBM begins with maximal safe resection followed by adjuvant radiotherapy and temozolomide, and maintenance temozolomide. IGV-001 is an autologous biologic-device combination immunotherapy for the treatment of ndGBM that consists of autologous GBM tumor cells and an antisense oligonucleotide against IGF-1R mRNA, irradiated and administered via biodiffusion chambers implanted in the abdomen. In a phase 1b study, IGV-001 was well tolerated without unexpected adverse events in subjects with ndGBM. Multiple efficacy signals were observed, including significant improvements in progression-free survival (PFS), overall survival (OS), radiographic evidence of tumor response, and changes in immune response biomarkers. Here, we present early safety data from the phase 2b randomized, multicenter, double-blind, placebo-controlled study (NCT04485949) designed to assess efficacy and safety of IGV-001 in subjects with ndGBM across 20 sites in the United States. After surgical resection, subjects were randomized 2:1 and treated with IGV-001 or placebo followed by SOC. The primary outcome is PFS, defined as the time from randomization to first progression, as determined by blinded central radiology review, or death. Secondary outcomes include OS, defined as the time from randomization to death due to any cause, and safety. As of May 22, 2024, 99 subjects were randomized and 95 implanted with IGV-001 or placebo plus SOC. A total of 39/45 (86.7%) subjects had sufficient follow-up time after initiated treatment with concurrent radiation and temozolomide. Nine of 72 randomized (12.5%) discontinued treatment, including 7 who stopped during the SOC treatment period. None ceased treatment for adverse events, protocol deviations, or death. A total of 11/72 (15.3%) randomized subjects discontinued the study after randomization. A review of blinded safety data did not show any emerging risk and supports no change to the benefit-risk profile of IGV-001 versus placebo. Updated data will be presented.
CTNI-03. DECREASED GROWTH VELOCITY IN A PHASE 1 TRIAL (PNOC014) OF TOVORAFENIB IN PATIENTS WITH RECURRENT OR PROGRESSIVE MAPK-ALTERED TUMORS
Authors: Wright Karen , Kline Cassie , Abdelbaki Mohamed Shebl , Sayour Elias , Crotty Erin , Raabe Eric , Elster Jennifer , Prados Michael , Haas-Kogan Daphne , Mueller Sabine 
Published: November 2024

Abstract

BACKGROUND
The mechanisms by which MAPK-targeted agents affect children in active phases of neurocognitive and physical development are poorly understood and hence, may place them at risk, particularly for uncommon patient toxicities that may require longer monitoring or larger patient cohorts to understand the long-term implications. Decreased growth velocity was identified in our investigator-initiated phase 1 trial (NCT03429803) of tovorafenib in relapsed MAPK-altered tumors.

METHODS
Forty-four patients enrolled from February 2018-October 2021. Toxicity was assessed according to CTCAE version 5 term growth suppression (GS). Patients were also evaluated retrospectively based on age-specific growth velocity norms. Post-pubertal patients (n=14), those with pre-existing growth abnormalities (n=3), and those on drug less than 6 months (n=10) were excluded (total n=27; 61%). Growth velocities for each patient were calculated prior to, on, and after discontinuing treatment as available.

RESULTS
Our safety database included 17 reported events of GS. Sixteen patients experienced grade 3 GS, defined as growth velocity reduction ≥50% ideally measured over a year compared to baseline. One patient experienced grade 2 GS, defined as reduced growth velocity by 30-49% compared to baseline. Separate retrospective analysis using age-specific growth velocity norms further confirmed that all 17 patients (100%) demonstrated decreased growth velocity compared to age-specific norms following start of treatment regardless of dose (3, 5 and 9 patients at 280, 420 and 530 mg/m2/dose, respectively with a mean dose of 507 mg, range: 220-840 mg). Four of 9 patients on 530 mg/m2 were dose reduced for other reasons and hence treated at 420 mg/m2. In 14/15 patients off drug, growth rates recovered at near normal or normal rates within 12 months of discontinuation.

CONCLUSIONS
Patients on tovorafenib experience decreased growth velocity, which is recoverable off drug. Long-term monitoring of growth and further preclinical investigations to mitigate this toxicity and understand its effect are warranted.
CTNI-07. LONG-TERM EFFICACY AND SAFETY OF LAROTRECTINIB IN PATIENTS WITH TRK FUSION PRIMARY CENTRAL NERVOUS SYSTEM (CNS) TUMORS: AN UPDATED ANALYSIS
Authors: Perreault Sébastien , Spano Jean-Philippine , Nilsson Anna , Deyell Rebecca J , Doz François , Geoerger Birgit , Gumus Mahmut , Lassen Ulrik N , Nysom Karsten , Valero-Arrese Lorena , Idbaih Ahmed , Bernard-Gauthier Vadim , Neu Natascha , Brega Nicoletta , Drilon Alexander , Laetsch Theodore W , van Tilburg Cornelis M 
Published: November 2024

Abstract

BACKGROUND
Larotrectinib is a highly selective TRK inhibitor approved for TRK fusion tumor-agnostic use. We report updated data on larotrectinib-treated patients with TRK fusion primary CNS tumors.

METHODS
Patients enrolled in 2 clinical trials (NCT02637687 [SCOUT], NCT02576431 [NAVIGATE]) were included. Responses were independent review committee (IRC)-assessed (RANO). Patients from SCOUT could stop larotrectinib in the absence of on-treatment progression (wait-and-see). Data cutoff: July 2023.

RESULTS
Fifty-five patients (38 aged &lt;18 years at enrolment) were evaluated, including 16 with non-measurable disease at baseline. Tumor histologic groups included: high-grade glioma (HGG; n=32), low-grade glioma (LGG; n=15), and other (n=8). For all patients (n=55), ORR was 27% (95% CI 16-41): 3 CR, 12 PR, 24 SD (15 for &gt;24 weeks), 12 PD, and 4 not evaluable. For pediatric patients (n=38), ORR was 37% (95% CI 22-54). ORR in patients with measurable disease only was 38% (95% CI 23-55) for all patients (n=39) and 52% (95% CI 32-71) for pediatric patients (n=27). The 24-week disease control rates were 55% (95% CI 41-68) and 74% (95% CI 57-87) for all patients and pediatric patients, respectively. Median time to response, DoR, PFS, and OS were 2, 12 (95% CI 6-not estimable [NE]), 12 (95% CI 7-20), and 38 months (95% CI 23-NE), respectively. Treatment duration ranged from 1 to 64+ months. At data cutoff, 1 pediatric patient with HGG and 4 with LGG entered wait-and-see; median duration of first wait-and-see period was 20 months (range 4-29). One pediatric patient with LGG resumed treatment following disease progression in wait-and-see. Treatment-related adverse events were predominantly Grade 1/2.

CONCLUSION
Larotrectinib demonstrated rapid, durable responses and manageable safety in patients with TRK fusion primary CNS tumors. This supports the adoption of NGS panels containing NTRK gene fusions when testing patients to identify those who might benefit from TRK inhibitor therapy.
CTNI-08. DOSE ADJUSTED TEDDI-R FOR PRIMARY CNS DIFFUSE LARGE B-CELL LYMPHOMA
Authors: Green Richard , Miranda Candy 
Published: November 2024

Abstract
We report our initial experience treating 4 patients with the dose adjusted TEDDI-R protocol as reported by Dunleavy et al in 2015. The median age was 63 years, 2 patients were male, median KPS 60. Two patients were newly diagnosed: one of these had inadequate renal function for methotrexate; and the other had experienced acute methotrexate leukoencephalopathy. Two patients were treated for their first recurrence, having progressed during therapy with the MT-R protocol; one of these received salvage WBRT prior to starting. The protocol consisted of temozolomide 90 mg/sq m IV, cycles 1-6, days 2-5; etoposide 45 mg/sq m/day IV cycles 1-6, Days 2-5; liposomal doxorubicin 40 mg/sq m IV, cycles 1-6, day 2; dexamethasone 10 mg PO bid, cycles 1-6, days 1-5; ibrutinib 560 mg qd starting 3 days before cycle 1, day 1, then 560 mg qd, cycles 1-6, days 1-10; rituximab 375 mg/sq m IV cycles 1-6, days 1-2; and cytarabine 70 mg via Ommaya reservoir, cycles 2-6, days,1 and 5. Aspergillosis prophylaxis with isavuconazonium 372 mg mg PO bid was used. Overall, only 1 patient completed all 6 planned cycles; the median number of cycles completed was 4.5. Both newly diagnosed patients died during therapy; one died after 1 cycle from CMV colitis, and the other after 5 cycles from tumor recurrence, pneumonia, and septic shock. One patient with recurrent disease achieved a complete response and went on to high dose chemotherapy and autologous bone marrow transplantation; the other had a partial response after 4 cycles but died from pulmonary embolism. Median PFS for the newly diagnosed patients was 177 days, and for the recurrent patients, 221 days. Median OS for the cohort was 242 days. These preliminary data suggest that the TEDDI-R protocol was relatively toxic, especially for patients with poor neurological function, but can be an effective salvage therapy after progression on methotrexate-based therapy.
CTNI-18. RESULTS FROM A PHASE 1 STUDY OF SONODYNAMIC THERAPY WITH WHOLE HEMISPHERIC LOW INTENSITY NON-ABLATIVE ULTRASOUND IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA
Authors: Schulder Michael , Johans Tanner , Mechtler Laszlo , Agarwal Vijay 
Published: November 2024

Abstract
We report the first use of a novel device that delivers non-ablative low intensity diffuse ultrasound (LIDU) across the entire hemisphere in combination with the oral sonosensitizing agent 5-ALA for the treatment of recurrent high grade glioma. LIDU in combination with 5-ALA focally targets tumor cells with sonodynamic therapy (SDT), causing selective tumor cell death across the entire hemisphere via 1) direct tumor targeting and 2) stimulation of immunogenic cell death. In this 3x3 clinical trial designed for safety (n=12, NCT05362409), two patients were enrolled after multiple recurrences and seven patients had multifocal or multicentric disease. Treatments were delivered monthly for a minimum of four sessions. A treatment duration of 120 minutes was established after dose escalation and expansion. SDT delivered via a novel device and in conjunction with 5-ALA was well tolerated, with no duration-limiting toxicities or serious related adverse events. Compared to historical data, we observed a significant increase in overall survival (mOS of 14.0+ months, with 7 of 12 patients still alive at the time of this submission and final median OS not yet achieved). A Phase 2b randomized, multicenter, double-blind, placebo-controlled study has been planned to commence in 2025 to assess the safety and efficacy of LIDU with sonosensitization in patients with newly diagnosed GBM.
CTNI-21. PIVOTAL, PHASE 2B RENEU TRIAL OF MIRDAMETINIB IN CHILDREN AND ADULTS WITH NEUROFIBROMATOSIS TYPE 1-ASSOCIATED PLEXIFORM NEUROFIBROMA (NF1-PN): A SPOTLIGHT ON PATIENTS ACHIEVING DEEP RESPONSE
Authors: Gershon Timothy , Moertel Christopher , McNall-Knapp Rene , Shuhaiber Hans , Weintraub Lauren , Hajjar Fouad , Nickerson Molly , Weber Michael , Lokku Armend , Babovic-Vuksanovic Dusica , Hirbe Angela 
Published: November 2024

Abstract

BACKGROUND
Patients with NF1-PN in the phase 2b ReNeu trial (NCT03962543) of mirdametinib in adults (N=58, ≥18y) and children (N=56, 2-17y) had a deeper median (range) best reduction (adults: -41% [-90% to 13%]; children: -42%, [-91% to 48%]) from baseline in target PN volume than previously published in trials of other agents in NF1-PN.

METHODS
In the 24-cycle (1-cycle=28d) treatment phase, objective response rate (ORR) was the percentage with confirmed objective responses (OR) of ≥20% target PN volume reduction from baseline on consecutive MRIs (by blinded independent central review). This analysis includes patients achieving deep response (&gt;50% best reduction from baseline in target PN volume) regardless of OR and inclusive of patients in the long-term follow-up. Exploratory analysis of baseline characteristics compared patients with deep response and patients with ≤50% volume reduction.

RESULTS
ORR was 41% (24/58) in adults and 52% (29/56) in children treated with mirdametinib. 62% (15/24) of adults and 52% (15/29) of children who achieved OR had deep response. To further characterize deep response, 2 adults and 3 children with deep response without confirmation or in long-term follow-up were included. Of those with a deep response, 35% (6/17) of adults and 72% (13/18) of children were investigator-defined as having progressing PN. Patients achieved deep response regardless of baseline age, sex, target PN volume, tumor location, or progression status. For adults and children, median time to best percent change from baseline in PN volume for patients achieving deep response was 25.4 and 21.8mo; for patients with reductions of ≥20% to ≤50% was 15.3 and 15.2mo; for patients with reductions of &lt;20% was 7.8 and 4.2mo, respectively.

CONCLUSIONS
Patients had a similar likelihood of achieving deep response across assessed baseline characteristics. A trend between deep response and longer treatment duration suggests a benefit of prolonged therapy with mirdametinib.
CTNI-22. DABRAFENIB (D) AND TRAMETINIB (T) EITHER IN COMBINATION OR AS MONOTHERAPY IN PEDIATRIC PATIENTS HARBORINGBRAF ALTERATIONS IN GLIOMAS OR OTHER RARE TUMORS: FINDINGS FROM AN EARLY ACCESS PROGRAM (EAP)
Authors: Russo Mark , Ferreira AnaRita , Roughton Michael , Rizk Sviatlana , Aoun Manar 
Published: November 2024

Abstract

BACKGROUND
In 2022, dabrafenib and trametinib (D+T) combination received an accelerated US FDA approval for use in adult and pediatric patients with BRAF V600E–mutated unresectable or metastatic solid tumors with no viable alternative therapy. However, to provide global access to therapy in countries where the suitable formulations and/or indications are not yet approved, EAPs are established. We report on patient data from an EAP for pediatric patients with BRAF V600-mutated gliomas or other rare tumors with BRAF alterations such as BRAF fusions, seeking clinical benefit from therapy with dabrafenib and/or trametinib.

METHODS
We analyzed data from the global EAP, where pediatric patients with BRAF alterations in solid tumors including gliomas or other rare tumors received D+T combination or monotherapy. Key eligibility criteria included: age &lt;18 years, absence of approved indications, presence of BRAF V600E/K mutation or other BRAF alterations, and exhaustion of standard therapies. Requests were processed through a global system from November 2016 to December 12, 2022 (cutoff date). Key data on patient characteristics and median treatment duration (mDoT) were collected and will be presented.

RESULTS
Overall, 482 patients with solid or hematological malignancies were included, of which 35.1%, 31.7%, and 33.2% received combination therapy and dabrafenib and trametinib monotherapies, respectively. Across the treatment cohorts, median age was 4.2-6.6 years, and 49.4%-52.9% were males. Most patients had low-grade (72%) or high-grade (4.6%) gliomas, followed by Langerhans cell histiocytosis (17.8%) and other tumors (5.6%). The estimated mDoT for liquid and solid formulations were, respectively, 14.6 months and 10.1 months in combination therapy, 16.5 months and 12.8 months in dabrafenib monotherapy, and 8.8 months and 7.4 months in trametinib monotherapy.

CONCLUSIONS
EAP data represent a valuable real-world resource in understanding patient characteristics in rare tumors (pediatric gliomas). A significant number of treatment requests indicate substantial unmet need, and significant mDoT across age categories was suggestive of benefit to pediatric patients on therapy.
CTNI-41. LONG-TERM SURVIVAL AND PATTERNS OF PROGRESSION IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA TREATED WITH OR WITHOUT TUMOR TREATING FIELDS (TTFIELDS) IN A REAL-WORLD SETTING
Authors: Riegel Devon , Bureau Britta , Conlon Patrick , Chavez Gordon , Connelly Jennifer 
Published: November 2024

Abstract

BACKGROUND
Tumor Treating Fields therapy (TTFields) is an FDA-approved locoregional treatment for patients with newly diagnosed glioblastoma (ndGBM). Previous trial data showed the addition of TTFields to standard TMZ-based therapy to significantly improve overall survival (OS), but real-world data is lacking, particularly with long follow-up duration. Here, we report real-world survival and patterns of progression for patients with ndGBM treated with or without TTFields.

METHODS
Patients diagnosed with GBM and treated with standard of care therapy at the Medical College of Wisconsin between March 2015–March 2023 were included. Progression-free survival (PFS) and OS outcomes were assessed, and compared across groups who received or did not receive TTFields therapy during maintenance treatment. Patterns of disease progression were analyzed via anatomic assessment. Patients were followed through March 1, 2024.

RESULTS
A total of 210 patients (TTFields: n=110/52.4%; No-TTFields: n=100/47.6%) were included for analysis. Median age was 60 and 63 years for the TTFields and No-TTFields groups, respectively, with each group 43% female. Other baseline characteristics were consistent across groups. Median TTFields duration was 6.8 months (range: 1–94). OS was significantly improved for the TTFields group vs No-TTFields group (median OS: 21.6 months [18.4–24.8] vs 17.7 months [15.0–20.8]; HR 0.73 [95% CI: 0.54–0.99, P=0.042]). Median PFS was 12.1 months (10.3–14.4) vs 9.6 months (8.5–12.8) with HR 0.77 (95% CI: 0.58–1.02; P=0.071). 5-year OS was 17% (10–28) for the TTFields group, and 11% (5–22) for No-TTFields group. Patients treated with TTFields exhibited a higher rate of non-local progression compared with the No-TTFields group (28% vs 15%, [P=0.044]).

CONCLUSIONS
Analysis of patients from a large institutional dataset reveals an association between TTFields use and long-term survival benefit. Higher incidence of non-local patterns of progression among TTFields users is consistent with pivotal trial findings.
CTNI-42. A BIOMARKER-GUIDED PHASE 2 STUDY OF DB107-RRV (A RETROVIRAL REPLICATING VECTOR) COMBINED WITH DB107-FC (FLUCYTOSINE EXTENDED-RELEASE TABLETS) IN PATIENTS WITH RECURRENT GLIOBLASTOMA OR ANAPLASTIC ASTROCYTOMA: A CLINICAL PROTOCOL
Authors: Shah Ashish , Ramsoomair Christian , Seetharam Deepa , Hudson Anna , Lu Victor , Nasany Ruham , Kushnirsky Marina , Hill Colin , Komotar Ricardo , Ivan Michael , Wright Leonela , Andrews David , Carattini Yamina , Valiathan Ranjini , Koru-Sengul Tulay , De La Fuente Macarena 
Published: November 2024

Abstract

INTRODUCTION
Despite significant advances in understanding the basic pathogenesis of glioblastoma, the median survival of patients has minimally changed in the past 25 years with a 5-year survival rate of &lt;7%. Because of the dismal prognosis, attention has shifted to alternative adjuvant treatment modalities including gene/viral-based therapy. The first clinically tested replicating retroviral vector DB107-RRV (vocimagene amiretrorepvec, formerly Toca511) was assessed in a randomized Phase 3 study (NCT02414165) to evaluate the intracranial administration of DB107-RRV with subsequent oral administration of DB107-FC (5-fluocytosine extended-release tablets) in patients with recurrent HGG. Although the primary endpoint of overall survival (OS) in the intent-to-treat population was not met (median OS=11.07 months, DB107-RRV+ DB107-FC arm and 12.22 months for the SOC arm (HR=1.06; 95% CI:[0.83, 1.35], p=0.6154)), post-hoc analysis identified a subgroup of patients (responders) who demonstrated a marked survival benefit from the Phase III clinical trial (Toca 5, NCT02414165). Using a non-invasive genotyping pipeline, a novel biomarker, DGM7, was identified among responders that confers an improved prognosis: (DB107-RRV+DB107-FC is 18.3 months vs. 12.0 months in the SOC group (HR=0.50; 95% CI:[0.28, 0.89], p= 0.0167)). DGM7 is present in the blood of approximately 20-30% of HGG patients.

METHODS
This is a Phase 2, single-site, open-label, single-arm study to assess the oral administration of DB107-FC in combination with DB107-RRV in DGM7+ patients with recurrent/progressive HGG. Key inclusion criteria include presence of the DGM7 biomarker in blood, patient age 18–75 with histologically proven, measurable (MRI) recurrent/progressive HGG, and no radiation therapy for at least 12 weeks without histopathologic/MRI progression confirmation. The primary endpoint of this study will be progression-free survival at 6 months (PFS6) and OS of DB107-RRV+DB107-FC in DGM7+ patients with recurrent/progressive HGG compared to the historical study arm SOC/DGM7+ from NCT02414165.