Despite evidence that antibody drug conjugates (ADCs) are active in brain metastases, their role in primary central nervous system (CNS) tumors remains unclear. We report two adults with molecularly defined ependymoma - a MYCN-amplified spinal tumor with intracranial dissemination and a supratentorial ZFTA-RELA-fused tumor with multiple recurrences - who demonstrated radiographic response and/or durable clinical and metabolic stability with trastuzumab deruxtecan (T-DXd). HER2 expression was identified by immunohistochemistry in both tumors, consistent with prior systematic profiling of ADC targets in CNS tumors. Multiplexed imaging showed broad but heterogeneous HER2 expression across tumor states in both cases; in the MYCN-amplified tumor, this occurred alongside EGFR/MAPK-enriched proliferative niches, whereas the ZFTA-RELA tumor showed more diffuse organization without strong coupling of EGFR and proliferation. These findings provide early clinical evidence supporting HER2-directed ADCs in ependymoma and highlight the value of integrated molecular and spatial profiling in interpreting therapeutic response in rare CNS tumors.

Brain tumors are among the most lethal cancers, exhibiting low survival rates compared to all cancer types. In this study, we investigate CD3+ lymphocytes (based on immunohistochemistry stained microscopic images), crucial components of the immune response that contribute significantly to tumor defense mechanisms. Neurologists have identified specific infiltration patterns of CD3+ lymphocytes in gliomas. To predict these patterns, we implemented a two-step strategy. In the first step, we aimed to distinguish microscopic images with or without CD3+ lymphocytes using two input types. A 2D CNN was trained on density maps derived from CD3+ segmentation, while an XGBoost model was applied to features extracted by a VGG16 pretrained network. Both models performed well, achieving accuracy greater than 0.8. In the second step, we analyzed spatial patterns of lymphocyte aggregation on image patches. This pattern analysis accurately predicted aggregation classes with an accuracy of more than 0.8. Perspective of this study will offer insights into survival outcomes.

A working group of cIMPACT-NOW evaluated the literature on IDH-mutant gliomas for opportunities to improve pathology-based risk stratification and grading, especially at the interface of CNS WHO grade 2 and 3, since therapeutic decisions depend on risk assessment for clinical management. The group also evaluated newly described IDH-mutant glioma subgroups and considered multidisciplinary aspects of therapeutic decision-making. PDGFRA amplification was associated with highly aggressive clinical behavior of IDH-mutant astrocytomas, consistent with CNS WHO grade 4. Other genetic alterations associated with intermediate risk and most consistent with CNS WHO grade 3 included PIK3 mutations, EGFR amplification, MYCN amplification and specific RB pathway alterations, including CDK4, CDK6 and CCND2 amplification, RB1 homozygous deletion or mutation, and mutation of CDKN2A. DNA methylation signatures of G-CIMP-low or A_IDH_HG were consistent with CNS WHO grade 3 or 4, depending upon other grading criteria. We suggest a mitotic count of ≥ 3 per 2.4 mm2 could be considered as a CNS WHO grade 3 criterion. Our review did not uncover features to improve grading of oligodendroglioma, IDH-mutant and 1p/19q-codeleted, although CNS WHO grade 3 tumors with elevated mitotic rates, yet lacking necrosis, microvascular proliferation, CDKN2A/B homozygous deletion and MRI contrast enhancement, may be associated with extended survival. Implementing evidence-based criteria for risk stratification and grading will improve guidance for clinical decision-making.

Individual longitudinal changes in PET MTV and FLAIR volumes during treatment. For each patient, changes in PET-derived MTV (red line) and FLAIR lesion volume (blue line) are plotted over time, with treatment initiation marked as day 0. Numeric values indicate the change in volume at each time point, referenced either to baseline or to the lowest value observed (best response) in cases with multiple follow-ups. Each panel represents the data for a single patient.

PURPOSE:Integrating external control data into clinical trial designs and analyses has the potential to accelerate drug development processes. We reanalyzed the three experimental arms of the Individual Screening Trial of Innovative Glioblastoma Therapy (INSIGhT), a randomized phase II platform trial in newly diagnosed O6-methylguanine-DNA methyltransferase-unmethylated glioblastoma (ClinicalTrials.gov identifier: NCT02977780). To evaluate the validity of using external data sets, we compared treatment effect estimates based on internal INSIGhT control data and matched external control data. METHODS:The three experimental arms of INSIGhT (abemaciclib [n = 72], neratinib [n = 80], and CC-115 [n = 12]) did not improve survival compared with internal controls (standard chemoradiation [n = 70]). We derived external control patient-level data from multiple real-world and clinical trial data sets. We applied propensity score matching and Cox proportional hazards models to estimate treatment effects with external controls. Additionally, using this glioblastoma (GBM) data collection, we specified simulation scenarios to evaluate trial designs that integrate external controls. RESULTS:After matching to external controls, no survival benefit was observed for patients receiving abemaciclib (hazard ratio [HR], 1.00 [95% CI, 0.75 to 1.34]), neratinib (HR, 0.93 [95% CI, 0.70 to 1.24]), or CC-115 (HR, 0.88 [95% CI, 0.41 to 1.88]). Simulations, together with the INSIGhT data and a collection of GBM data sets, allowed us to examine efficiencies and risks of clinical trial designs that leverage external control data. CONCLUSION:The use of carefully matched external controls, to replace or augment the internal controls of INSIGhT, produced treatment effect estimates that were similar to previously published analyses. Single-arm trial designs and hybrid randomized designs incorporating propensity score-matched external control data evaluated treatment effects in the early-phase testing of experimental therapies in newly diagnosed GBM. The validity of this approach and risks of bias depended on the availability of comprehensive and accurate data on all potential confounders, in the absence of unmeasured confounding.

Exploratory comparison of baseline 18F-DOPA-PET values in progressors (n=6) vs non-progressors (n=14) on IDH inhibitor treatment. Parameters include metabolic tumor volume (MTV), total lesion glycolysis (TLG), tumor-to-background maximum ratio (TBRmax), and mean ratio (TBRmean). P-values were calculated using the Mann-Whitney U test.

Recurrent gliomas have limited treatment options and dismal outcomes. We report the efficacy and safety of the anti–programmed cell death protein-1 antibody pembrolizumab in participants with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) recurrent glioma in KEYNOTE-158. The phase 2, multicohort KEYNOTE-158 study (NCT02628067) is evaluating pembrolizumab monotherapy in participants with advanced rare cancers. This analysis focused on participants with recurrent glioma from cohort K where eligible participants were ≥18 years old with MSI-H/dMMR tumors and measurable disease per RECIST v1.1. Participants received pembrolizumab 200 mg every 3 weeks for up to 35 cycles. The primary endpoint was objective response rate (ORR) per RECIST v1.1 by independent central radiologic review. Twenty-one participants with recurrent glioma were enrolled. Median (range) follow-up was 50.0 (15.4‒65.5) months. Best overall responses were partial response (PR; n = 1, 5

PURPOSE:Small-molecule inhibitors targeting isocitrate dehydrogenase (IDH) 1/2-mutant proteins have demonstrated benefit in IDH1/2-mutant gliomas. However, responses assessed by conventional MRI measurements are infrequent, delayed, and difficult to interpret, highlighting the need for early biomarkers of treatment benefit. In this study, we investigated 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine positron emission tomography (18F-DOPA-PET) and MRI responses in patients with IDH1/2-mutant glioma receiving IDH inhibitors (IDHi). EXPERIMENTAL DESIGN:Patients with IDH1/2-mutant glioma receiving IDHi as part of trials or expanded access programs with pre- and posttreatment MRI and 18F-DOPA-PET were included. Evaluations included 2D/3D measurements on T2-weighted fluid-attenuated inversion recovery images; T1-post-contrast, perfusion, and diffusion imaging for MRI; and metabolic tumor volume (MTV), total lesion glycolysis, and tumor-to-background ratios (TBR) for 18F-DOPA-PET. Disease response evaluation using volumetric assessments, RANO 2.0, and PET RANO 1.0 criteria were compared and correlated with outcomes. RESULTS:From 2021 to 2025, 20 patients with IDH1/2-mutant glioma (8 with astrocytoma and 12 with oligodendroglioma) receiving IDHi (4 receiving ivosidenib and 16 receiving vorasidenib) were analyzed. Significant reductions in 18F-DOPA-PET parameters including TBRmean, TBRmax, and MTV were observed in 10 of 20 patients, aligning with observed changes in perfusion and diffusion imaging. Nine partial responses and one complete response were identified using 18F-DOPA-PET, whereas both volumetric and standard 2D morphologic MRI assessments indicated stable disease as best response. PET response on MTV was correlated with prolonged tumor control. CONCLUSIONS:These results highlight the potential of 18F-DOPA-PET and advanced MRI sequences as valuable complements to standard RANO 2.0 MRI evaluations for assessing treatment response in patients with glioma undergoing IDHi therapy.

2010 Background: Grade 2 gliomas with isocitrate dehydrogenase 1/2 mutations (mIDH1/2) are diffuse, slowly progressive, malignant brain tumors with a poor long-term prognosis. In the Phase 3 INDIGO trial (NCT04164901) of patients (pts) with grade 2 mIDH1/2 glioma, vorasidenib (VOR), an oral, brain-penetrant, dual inhibitor of mIDH1/2, demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint, progression-free survival (PFS) per blinded independent review committee (BIRC), and key secondary endpoint, time to next intervention (TTNI), vs placebo (PBO) at the preplanned interim analysis (data cut-off [DCO]: September 6, 2022). An additional 6 months of data up to study unblinding, March 7, 2023, showed that median PFS was not reached (95% confidence interval [CI]: 22.1 mos, not estimable [NE]) with VOR vs 11.4 mos (95% CI: 11.1, 13.9) with PBO, and median TTNI was NE (95% CI: NE, NE) with VOR vs 20.1 mos (95% CI: 17.5, 27.1) with PBO. Here, we present updated efficacy and safety results as of January 17, 2025, from pts randomized to VOR. Methods: Key eligibility criteria included residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma after surgery only; aged ≥12 years; Karnofsky performance score ≥80; measurable non-enhancing disease; surgery as only prior treatment; no immediate need of chemoradiotherapy (CT/RT). Pts were randomized 1:1 to VOR 40 mg daily in 28-day cycles or PBO. After study unblinding, pts receiving PBO were permitted to cross over to VOR. Primary endpoint: radiographic PFS per BIRC. Key secondary endpoint: TTNI. Results: 331 pts were randomized: 168 to VOR and 163 to PBO (median age: 40.0 years [range: 16–71]; oligodendroglioma: 172; astrocytoma: 159). As of January 17, 2025, 98/168 (58.3%) pts remained on VOR, and median follow-up was 41.6 mos (95% CI: 40.5, 42.7). Median PFS per investigator (INV) in pts randomized to VOR was 49.9 mos (95% CI: 39.6, NE), and median TTNI was NE (95% CI: 52.0 mos, NE). At 42 mos, 59.2% (95% CI: 49.9, 67.4) of pts were progression-free and 75.1% (95% CI: 67.4, 81.2) were not in need of CT/RT or surgery. Objective response rate per INV was 31.5% (95% CI: 24.6, 39.2). Median overall survival was not reached. PFS and overall response per BIRC will be presented. The safety profile of VOR was consistent with previous reports. No new safety signals were observed. Conclusions: In the randomized, Phase 3 trial of a targeted therapy in grade 2 mIDH1/2 glioma, over 3 years of follow-up in pts randomized to VOR support the robustness of PFS and TTNI results and confirm a durable and sustained treatment benefit with VOR. VOR is now approved in over 40 countries as a monotherapy for pts with grade 2 mIDH1/2 glioma following surgery. Clinical trial information: NCT04164901 .

The mutant isocitrate dehydrogenase 1/2 inhibitor (mIDHi) vorasidenib was recently incorporated into clinical treatment guidelines for IDH-mutant gliomas, although its impact on chemoradiation is unclear. Specifically, it is unknown whether upfront mIDHi exposure alters subsequent chemoradiation efficacy. Addressing this critical question has been challenging because of limited clinical data and a paucity of mIDHi-responsive preclinical glioma models. We first established that a genetic mouse model of IDH-mutant astrocytoma developed by our group was responsive to vorasidenib monotherapy. We then used this mouse to address whether mIDHi alters the response to chemoradiation after progression on mIDHi. Mice that received upfront vorasidenib followed by chemoradiation at progression had improved survival compared with control mice receiving vehicle followed by chemoradiation. We then compiled real-world data and early outcomes from 29 patients who were among the first to receive mIDHi followed by radiation with or without chemotherapy. Our study directly addresses uncertainty surrounding therapy sequencing that has emerged after introduction of vorasidenib as a first-line treatment for IDH-mutant glioma. Our empirical preclinical data demonstrate that prior mIDHi treatment enhances chemoradiation sensitivity of IDH-mutant glioma.

e14097 Background: Ependymomas are rare central nervous system (CNS) tumors lacking approved targeted therapies, and recurrent disease remains difficult to treat. Recent systematic profiling has identified HER2 protein expression in a subset of ependymomas, suggesting a potential role for HER2-directed antibody–drug conjugates (ADCs). Trastuzumab deruxtecan (T-DXd), a next-generation HER2-targeted ADC with documented CNS activity in breast cancer, has not been systematically evaluated in primary CNS tumors. Methods: Two patients with recurrent, molecularly defined ependymoma who had progressed after standard therapies were treated off-label with trastuzumab deruxtecan (T-DXd). The cohort included one patient with MYCN-amplified spinal ependymoma with intracranial dissemination and another with supratentorial ZFTA-RELA–fused ependymoma. Clinical, radiographic, and metabolic responses were assessed using serial MRI and 18 F-FDOPA PET imaging. In the MYCN-amplified case, high-dimensional spatial profiling with multiplexed immunofluorescence (CyCIF) was performed to characterize tumor-cell intrinsic programs related to lineage state, proliferation, and signaling. Results: Both tumors demonstrated membranous HER2 expression by immunohistochemistry (estimated 2+–3+). In the MYCN-amplified case, HER2 expression was widespread across tumor compartments, while spatial profiling identified EGFR/MAPK-linked proliferative niches enriched for cycling and dedifferentiated tumor cell states. Treatment with T-DXd induced marked radiographic responses, with reductions of 84% and 54% in intracranial measurable lesions. The ZFTA-RELA–fused tumor demonstrated durable clinical stability on T-DXd over ~10 months, with a 27% reduction in enhancing tumor burden and a 46% decrease in metabolic tumor volume on serial 18 F-FDOPA PET imaging, meeting PET-RANO criteria for metabolic partial response. Treatment was generally well tolerated, with expected low-grade adverse effects. Conclusions: This study provides early clinical evidence that HER2-directed ADC therapy may benefit select patients with ependymoma across distinct molecular subtypes. Integration of molecular pathology with spatial tumor profiling revealed features that may inform patient selection and rational combination strategies. Together, these results support further prospective evaluation of HER2-targeted ADCs in molecularly selected ependymoma cohorts and highlight the value of protein-level and spatial profiling in identifying actionable vulnerabilities in rare CNS tumors.

TPS2102 Background: Glioblastoma (GBM) remains a fatal malignancy despite multimodality therapy. Approximately 60% of GBMs lack O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, thus associated with resistance to alkylating chemotherapy and poor survival with median OS of 12.7 months. Poly(ADP-ribose) polymerase (PARP) is a central regulator of DNA damage repair and genomic stability in GBM and represents a rational therapeutic target, particularly in the setting of radiotherapy-induced DNA damage. Niraparib is a selective PARP1/2 inhibitor that has demonstrated excellent central nervous system penetration and favorable tumor pharmacokinetic and pharmacodynamic properties in previously reported early-phase GBM studies. These findings provided the scientific rationale for Gliofocus, a global phase 3 trial designed to evaluate whether replacing temozolomide with niraparib during and after radiotherapy improves outcomes in patients with newly diagnosed, MGMT-unmethylated GBM. Methods: Gliofocus is a phase 3, open-label, randomized, two-arm study enrolling total 450 adults with newly diagnosed, MGMT-unmethylated GBM. Eligibility requires histologic diagnosis of GBM per 2021 WHO classification, Karnofsky performance status ≥70, documented MGMT promoter unmethylated status by validated local testing, and no prior GBM-directed therapy other than biopsy or resection. Patients are randomized 1:1 to receive niraparib or temozolomide concurrently with external-beam radiotherapy (60 Gy in 30 fractions using the ESTRO-EANO single-target volume approach), followed by adjuvant monotherapy of niraparib or temozolomide. Treatment continues until centrally reviewed disease progression per RANO 2.0 guidelines or completion of six cycles of temozolomide in the control arm. The primary endpoint is overall survival (HR = 0.698, 88% power). Secondary endpoints include progression-free survival, objective response rate, health-related quality of life, neurocognitive outcomes, and safety. Integrated correlative assessments include centralized imaging review, longitudinal neurocognitive testing, and patient-reported outcomes. Enrollment began in June 2024. The independent data monitoring committee last reviewed the study in January 2026, and recommended continuation as planned. The trial is sponsored by the Ivy Brain Tumor Center with funding/product support from GSK (NCT06388733). GSK was provided the opportunity to provide a courtesy review of the abstract; however, the authors are solely responsible for final content. Gliofocus study is being conducted across a minimum of 80 sites across 12 countries. Clinical trial information: NCT06388733 .

Glioblastomas remain the most lethal primary brain tumour in adults, with targeted therapies delivering only limited benefit despite deep molecular characterization. Several targeted drugs have received regulatory approval for low-grade gliomas, although progress in glioblastomas remains constrained by, among other aspects, extensive intratumoural heterogeneity, pathway redundancy, cellular plasticity and limited drug delivery to the central nervous system. Some of these challenges might be mitigated through strategies that enhance blood-brain penetration, including focused ultrasonography, convection-enhanced delivery, efflux avoidance and chemical modifications. Improved tumour profiling through multiregional sampling, prioritization of truncal dependencies and the development of novel therapeutic modalities, such as antibody-drug conjugates and theranostics, might also further improve outcomes. In this Review, we summarize the therapeutic landscape of targeted therapies in glioblastomas, spanning major target classes including receptor tyrosine kinases, intracellular signalling proteins, cell-cycle dysregulation and synthetic-lethal vulnerabilities. We also examine emerging strategies targeting genome integrity and telomeres, epigenetic modulators, and tumour-neural circuitry. Furthermore, we highlight tumour heterogeneity and extrachromosomal DNA dynamics as key drivers of oncogene amplification and therapeutic resistance as well as the roles of novel clinical trial designs and liquid biopsy-based monitoring strategies. Lastly, we discuss pathway-based glioblastoma classification and master kinase mapping as methods for aligning drugs with functional tumour states.

Glioblastoma (GBM), the most frequent and aggressive primary brain tumor, remains refractory to all current therapies including surgical resection, chemotherapy, radiotherapy and immunotherapy. Immunosuppressive mechanisms in the GBM tumor microenvironment contribute to the lack of anti-tumor adaptive immunity. We found that a subset of tumor associated macrophages (TAMs) can be repolarized into an anti-tumor phenotype via agonist stimulation of the retinoic acid-inducible gene I (RIGI), a cytosolic double-stranded RNA pattern recognition receptor (PRR). In silico analysis of adult GBM datasets available in the public domain revealed that RIGI expression by a subset of activated TAMs positively correlated with patient survival. Studies in syngeneic mouse models of GBM showed that intratumoral delivery of stem-loop RNA 14 (SLR14), a RIG-I agonist, improved the efficacy of chemotherapy, radiotherapy and immunotherapy treatments, beyond the effects of other nuclei acid sensor agonists. We found that RIGI + macrophages are the main drivers of SLR14 effect, combining activation of TAMs and priming of functional cytotoxic CD8+ T lymphocytes and NK cells. The anti-GBM effect of SLR14 is opening a significant new avenue for adult GBM treatment.

Multimodal imaging assessment. A) Comparison of FLAIR volumes obtained from PET MTV with diffusion (apparent diffusion coefficient [ADC], mm²/s) and perfusion (relative cerebral blood volume [rCBV]) maps, shown at baseline and follow-up for patients 2 and 8. B) Longitudinal evolution of T1-weighted gadolinium-enhanced (T1G) lesions during treatment for patients 2, 8, and 18 (images for patient 15 unavailable), displayed alongside their corresponding PET images.

PURPOSE:Age ≥40 years is regarded as a high-risk feature and an indication for adjuvant chemoradiotherapy for patients with lower-grade glioma in clinical practice guidelines. It is unclear whether age remains a relevant prognostic factor for contemporary definitions of lower-grade gliomas in the molecular era. METHODS:The Prospective Gliomas Research (PROGRES) database contains individual patient-level data from 11 prospective clinical trials or observational registries of histologically defined lower-grade 2-3 oligodendroglioma or astrocytoma. We determined the association of age (18-39 years v ≥40 years) with progression-free survival (PFS) stratified by isocitrate dehydrogenase 1 or 2 (IDH1/2) status, using log-rank tests and Cox regression models. We validated our findings in a separate multi-institutional retrospective cohort (Retrospective Glioma Research [REGRES] database). RESULTS:We identified 1,619 and 1,292 eligible patients in the PROGRES and REGRES cohorts, respectively. IDH-wildtype tumors were more common in patients 40 years and older (38% v 5%, odds ratio: 11.3 [95% CI, 6.5 to 19.7]). Age was associated with PFS in IDH-wildtype (5-year PFS for ≥40 v 18-39 years: 6% v 24%, hazard ratio [HR], 1.74 [95% CI, 1.21 to 2.50]) but not in IDH-mutant glioma (60% v 59%, HR, 0.89 [95% CI, 0.76 to 1.05], Pinteraction < .001). In IDH-wildtype tumors, older age predicted aggressive molecular features, including TERT promoter mutation (65% v 28%), EGFR amplification (41% v 15%), and chromosome +7/-10 alteration (57% v 25%). In a pooled analysis of four clinical trials, age was not predictive of a benefit from chemoradiotherapy versus radiotherapy alone for IDH-mutant glioma. CONCLUSION:In the absence of additional clinical or molecular risk factors, age alone should not be considered an indication for administration or deferral of adjuvant treatment. Practice guidelines should be revised to reflect contemporary prognostic factors in the molecular era.

Abstract BACKGROUND: Plixorafenib (FORE8394; PLX8394) is a novel, oral, small-molecule BRAF inhibitor and paradox breaker highly selective for BRAF V600 monomers and BRAF-containing dimers, including fusions. Plixorafenib binding disrupts RAF dimerization and prevents paradoxical MAPK pathway activation, avoiding the need for combination with a MEK inhibitor. Plixorafenib demonstrated in vitro activity against V600 and non-V600 mutant BRAF proteins, and anti-tumor activity has been demonstrated in BRAF V600 and non-V600 nonclinical models.In a phase 1/2a study, plixorafenib demonstrated promising safety and clinical activity across a range of doses tested in tumors with BRAF V600 mutations and BRAF fusions. The most common adverse events included predominantly grade 1-2 liver function test changes and grade 1 fatigue, nausea, diarrhea, and vomiting.The ongoing FORTE basket study is assessing the safety and efficacy of plixorafenib as monotherapy in participants with BRAF-altered advanced solid tumors. METHODS: The FORTE study is currently enrolling participants ≥10 years of age (to be expanded to ≥8 years upon N=6 pediatric patients and IDMC approval) into 4 baskets. Study details are shown in the Table. Eligible participants have received available therapies for advanced disease, have measurable disease, and have a Karnofsky (≥16 years) or Lansky (<16 years) Performance Score of ≥60 at study entry. All participants receive plixorafenib continuous dosing once daily within 30 minutes following a meal. Prior MAPK inhibitor therapy is excluded unless otherwise specified below.As of January 2026, the trial is recruiting participants in 11 countries globally, with 64 sites currently activated. To date, over 100 patients are enrolled. Clinical trial registry number: NCT05503797. Citation Format: Elisa Fontana, Macarena I. de la Fuente, Eric Sherman, Rona Yaeger, Malaka Ameratunga, Valentina Gambardella, Jessica Rine, Shubin Shahab, Morgan Winkler, Manish Monga, Dominik Modest, Jeffrey Yachnin, Mehdi Touat, Guillermo de Velasco, Jordi Rodon, Karisa C. Schreck. FORTE: A phase 2 master protocol assessing plixorafenib for BRAF-altered cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT273.