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Highly Conductive Ag Flakes‐Based Bio‐Adhesive for Multi‐Functional Epidermal Electronics

ABSTRACT Robust skin‐electronic interfaces are essential for signal fidelity of wearable bioelectronics, particularly under dynamic physiological conditions. In situ fabrication of biocompatible electronics offers a promising strategy to achieve conformal skin‐electronic integration through intimate interfacial contact. However, existing in situ‐printable conductive inks face inherent trade‐offs between high conductivity and strong adhesion, as well as between environmental resilience and on‐demand removability, significantly limiting their practical utility. Here, we report a viscoelastic supramolecular polymer‐based conductive adhesive ink (AgBioA) that simultaneously achieves high electrical conductivity (>15 000 S cm −1 ), strong skin adhesion (∼3 N cm −1 ), excellent environmental stability, ethanol‐triggered on‐demand dissolution, and superior biocompatibility. Our approach leverages a dynamically crosslinked supramolecular network, synthesized by copolymerizing α‐lipoic acid (LA) with 1,3‐diisopropenylbenzene (DIB) and reinforced with citric acid (CA) via hydrogen bonding. This unique design enables two key innovations: first, it ensures robust interfacial adhesion to diverse surfaces, from biological tissues to rigid electronic components; second, it facilitates the uniform dispersion of silver flakes into mechanically stable, percolated networks that guarantee highly reliable conductivity. Exploiting these advantages, we demonstrate fully integrated epidermal devices, including in situ fabricated bioelectrodes for reliable electrocardiography (ECG) and electrodermal activity (EDA) monitoring, and a skin‐conforming photoplethysmography (PPG) sensor where AgBioA functions dually as structural adhesive and conductive interconnect.

Topology-aware adaptive scheduling algorithm for heterogeneous AI-PC collaborative computing environments

PPIL2 suppression induces cellular senescence and inhibits proliferation in hepatocellular carcinoma via c-myc/p21 axis

AKY-2519, a novel B7-H3-targeted radioconjugate, and its biodistribution profile in patients with mCRPC.

3097 Background: AKY-2519 is a 6.1 kDa B7-H3 (CD276) targeting miniprotein with an N-terminal short polyethylene glycol linker and dodecane tetraacetic acid chelator designed to deliver actinium (Ac)-225 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) and other solid tumors. Miniproteins are a novel radioconjugate therapy (RCT) format affording high affinity, selectivity, deep tumor penetration and internalization prolonging tumor retention and rapid plasma clearance limiting exposure to normal tissues. B7-H3 is highly expressed in multiple solid tumor cancers and absent in normal tissues such as salivary glands. These properties render B7-H3 a promising target specifically for Ac-225 delivering RCT in mCRPC. We evaluated biodistribution and tumor uptake of AKY-2519 relative to PSMA-11 and assessed estimated radiation doses to tumors and normal tissues in 16 mCRPC patients. Methods: Sixteen mCRPC patients were imaged with [ 68 Ga]Ga-AKY-2519 and [ 68 Ga]Ga-PSMA-11 PET/CTs to assess biodistribution and tumor uptake by SUV. Patients then received low dose [ 177 Lu]Lu-AKY-2519 (~0.37-0.56 GBq) followed by SPECT/CT at 3, 24, and 144 hours post-injection for normal tissue and tumor dosimetry analyses. SPECT images were reconstructed with MIM SPECTRA Recon Software and mean human absorbed dose coefficients (Gy/GBq) were generated with MIM SurePlan MRT. To assess tumor doses, representative lesions including nodal, skeletal and primary disease sites were analyzed across multiple patients. Results: No AEs were reported throughout the imaging assessment. PET and SPECT/CTs showed robust tumor uptake with prolonged retention. High lesion concordance was observed between AKY-2519 and PSMA-11 supporting B7-H3 as a novel target in mCRPC and further suggesting co-expression of B7-H3 and PSMA. No accumulation of AKY-2519 was noted in normal tissues with initial activity in the liver rapidly clearing out. Of the normal tissues of interest including kidneys, salivary glands, liver and bone marrow, the mean absorbed doses were below established clinical thresholds when scaled up to a full therapeutic treatment course. The predicted absorbed tumor doses were within expected therapeutic ranges and exceeded normal tissue exposures indicative of a potentially favorable risk-benefit profile for [ 225 Ac]Ac-AKY-2519. Conclusions: These are the first clinical data showing concordance between PSMA and B7-H3 on PET-CT imaging in a substantial cohort of patients supporting B7-H3 as a novel target in mCRPC. The normal tissue to tumor dose ratios observed with AKY-2519 suggest a wide therapeutic window as an Ac-225 delivering therapeutic. The low predicted dose to salivary glands supports its use as an actinium delivering RCT for mCRPC, with dosing under IND expected to start in 2H-2026.

Analysis of corticosteroid exposure on efficacy of tarlatamab in small cell lung cancer: A multicenter retrospective study.

8088 Background: Tarlatamab, a delta-like ligand 3 (DLL3)-targeted bispecific T-cell engager, has shown meaningful activity in small cell lung cancer (SCLC). Immune-mediated toxicities such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) are common with T-cell–redirecting therapies and frequently require corticosteroids or cytokine-directed agents like tocilizumab. The impact of lymphodepleting corticosteroid exposure on tarlatamab efficacy remains unclear. Methods: We performed a retrospective analysis of patients with SCLC treated with tarlatamab from 2018–2025 across the University of Kansas and nine cancer centers included in the DLL3 PanTUMOR database. The primary endpoint was progression-free survival (PFS) stratified by cumulative dexamethasone dose. Other endpoints included overall response rate (ORR), characterization of CRS and ICANS, and overall survival (OS). A cost analysis of dexamethasone versus tocilizumab was also conducted. Results: Among 143 tarlatamab-treated patients, dexamethasone use for CRS or ICANS did not reduce PFS or ORR compared with patients not receiving corticosteroids. Tocilizumab did not reduce steroid needs. Median dexamethasone dose was higher in patients treated with tocilizumab. Severe CRS/ICANS was associated with significantly shorter OS. Cost analysis demonstrates the significant cost savings using dexamethasone compared to tocilizumab for treatment of immune-mediated toxicities. Conclusions: Corticosteroid exposure did not compromise tarlatamab efficacy, supporting optimized toxicity management without diminishing antitumor activity of DLL3-targeted T-cell–redirecting therapies. Endpoints Total Number of Evaluable Patients Outcomes Median PFS of tarlatamab with cumulative steroid dose Arm 1: No dexArm 2: 1-40 mg of dexArm 3: 41+ mg of dex Arm 1: 66Arm 2: 42Arm 3: 16 Arm 1: 2.53 moArm 2: 4.70 moArm 3: 3.68 moHR=1.0295% CI: 0.73-1.42 p=0.31 ORR of tarlatamab with cumulative steroid doseArm 1: No dexArm 2: 1-40 mg of dexArm 3: 41+ mg of dex Arm 1: 55Arm 2: 34Arm 3: 11 Arm 1: 29.1%Arm 2: 47.1% Arm 3: 36.4% Comparison of ORR with CRS (any grade) versus without CRS CRS: 58No CRS: 60 CRS: 34.5%No CRS: 33.3% Comparison of ORR with ICANS (any grade) versus without ICANS ICANS: 33No ICANS: 85 ICANS: 36.4%No ICANS: 32.9% Did the use of tocilizumab result in lower cumulative steroid use No tocilizumab: 42Tocilizumab: 28 Median dex dose without tocilizumab: 10 mgMedian dex dose with tocilizumab: 35 mg Median OS with grade 3+ CRS or ICANS versus with grade 0-2 CRS/ICANS Grade 0-2: 133Grade 3+: 10 Grade 0-2: 11.37 moGrade 3+: 4.19 moHR=0.3495% CI: 0.15-0.76p=0.006 Cost analysis for dex versus tocilizumabAverage wholesale price: tocilizumab $165,724, $3.13 dex10 mg CRS: 7237 doses of tocilizumab 37 doses of tocilizumab substituted with 37 dex 10 mg doses would have saved $173,962

Association of high-grade biology with marked salvage refractoriness following CD19 CAR T-cell therapy failure in large B-cell lymphoma: A systematic review and meta-analysis.

e19013 Background: CD19 chimeric antigen receptor (CAR) T-cell therapy has improved outcomes for relapsed or refractory large B-cell lymphoma (LBCL). While infusion-era responses appear comparable across biologic subgroups, outcomes following CAR T-cell failure remain poor. The impact of high-grade cytogenetic biology on responsiveness to subsequent therapy after CAR T-cell failure has not been quantified. Methods: We performed a systematic review and meta-analysis of multicenter cohorts reporting outcomes of adult patients with LBCL who relapsed or progressed after CD19 CAR T-cell therapy and received salvage treatment. Searches were conducted in PubMed/MEDLINE and Google Scholar with reference screening from January 2015 through November 30, 2025. Eligible studies reported comparative salvage outcomes stratified by biologic risk, defined as high-grade B-cell lymphoma with double- or triple-hit cytogenetics or double-hit lymphoma versus biologically standard-risk LBCL. The primary endpoint was complete remission (CR) to first salvage therapy following CAR T-cell failure. Risk ratios were pooled using inverse-variance fixed-effect models with continuity correction. Results: Approximately 70 studies were identified through database searching and screened for eligibility. Six studies were reviewed in full text, of which two large multicenter cohorts met inclusion criteria and were included in quantitative synthesis (total N = 282). Median age across cohorts was approximately 60 years, and 51 patients (18%) had biologically high-risk disease. In the Dodero cohort, CR to salvage therapy after CAR T-cell failure occurred in approximately 16% of patients with high-grade B-cell lymphoma compared with 37% of biologically standard-risk LBCL. In the Karmali cohort, patients with double-hit lymphoma achieved no complete remissions (0%) to first subsequent therapy after CAR T-cell failure, compared with approximately 19% among non-double-hit disease. Pooled analysis demonstrated a 62% relative reduction in likelihood of achieving CR among biologically high-risk patients compared with standard-risk LBCL (pooled RR 0.38, 95% CI 0.17-0.85), with no observed heterogeneity (I² = 0%). Conclusions: Biologically high-risk LBCL is associated with marked salvage refractoriness following CD19 CAR T-cell therapy failure, despite similar infusion-era outcomes. These findings suggest that adverse lymphoma biology, temporarily masked during CAR-T response, reasserts itself at relapse and identifies a population with limited responsiveness to conventional salvage approaches. Risk-adapted post-CAR T strategies and early clinical trial enrollment should be prioritized for patients with high-grade disease.

A molecular subtype–guided, chemotherapy-free neoadjuvant strategy using SHR-A1811 plus pertuzumab for hormone receptor–positive/HER2-positive breast cancer: A phase II trial in progress.

TPS653 Background: Hormone receptor–negative/HER2-positive breast cancer achieves high pathological complete response (pCR) rates with chemotherapy-based HER2-targeted therapy, whereas hormone receptor–positive (HR+)/HER2-positive disease consistently demonstrates lower pCR rates and substantial chemotherapy-related toxicity, representing an unmet clinical need. Antibody–drug conjugates (ADCs) may address this gap by enhancing HER2-directed cytotoxic delivery while potentially avoiding conventional chemotherapy. SHR-A1811 (ruikang-trastuzumab) is a next-generation HER2-directed ADC conjugated to a topoisomerase I inhibitor with a high drug-to-antibody ratio (≈6) and has demonstrated superior preclinical activity compared with trastuzumab emtansine. HER2-directed ADCs may be particularly advantageous in HR-positive/HER2-positive tumors, including those with HER2 immunohistochemistry (IHC) 2+ and in situ hybridization (ISH)–positive status, through bystander killing effects that may overcome heterogeneous or lower-level HER2 expression. Emerging evidence suggests that ADC activity is retained in HR-positive/HER2-positive breast cancer and may be enhanced when combined with pertuzumab, providing the rationale for evaluating neoadjuvant SHR-A1811 plus pertuzumab in this population. Methods: This prospective, open-label, single-arm phase II trial enrolls women aged > 18 and < 70 years with previously untreated stage II–III HR-positive/HER2-positive breast cancer. All patients receive neoadjuvant SHR-A1811 (4.8 mg/kg intravenously every 3 weeks) plus pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks) for four cycles. Baseline BluePrint profiling classifies tumors as luminal or non-luminal. Treatment is adaptively tailored based on molecular subtype and RECIST v1.1 response after four cycles. Patients with luminal subtype and stable disease switch to a chemotherapy-free regimen of trastuzumab, pyrotinib (a HER2-directed tyrosine kinase inhibitor), dalpiciclib (a CDK4/6 inhibitor), and an aromatase inhibitor, while patients with luminal subtype achieving partial or complete response and all non-luminal tumors continue SHR-A1811 plus pertuzumab for two to four additional cycles before surgery. Circulating tumor DNA (ctDNA) is assessed at baseline, after four cycles, and preoperatively. The primary endpoint is pCR (ypT0/is ypN0); secondary endpoints include event-free survival, objective response rate, and safety, with exploratory analyses evaluating associations among molecular subtype, ctDNA dynamics, and treatment response. Clinical trial information: NCT07307287 .

Osimertinib plus savolitinib in osimertinib-resistant non-small-cell lung cancer with low level gene copy number MET: A multi-center, open-label, and phase 2 study.

e20079 Background: MET-based resistance following osimertinib treatment for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC) is common, but less than 25% patients with MET amplification positive (gene copy number (GCN) > 5 or MET/CEP7 > 2) which can be treated by osimertinb plus savolitinib. It’s critical important to elicit an effective method for patients with low level copy number gain of MET gene after osimertinib progression. Methods: This is a multi-center, single-arm, open-label study involving patients following disease progression on osimertinib and chemo-immunotherapy. Enrolled patients were all EGFR-mutated advanced NSCLC progressed on osimertinib and chemo-immunotherapy, with MET GCN less than 5 and MET/CEP7 less than 2 tested by FISH; all were treated by savolitinib 600 mg (Body weight ≥ 60 Kg) or 400 mg (Body Weight <60 Kg) plus osimertinib 80 mg oral daily. The Primary endpoint was response rate (ORR), and the second endpoints were progression-free survival (PFS), safety and overall survival (OS). Results: Between December 1, 2023 and December 20, 2025, 57 patients of EGFR-mutated advanced NSCLC progressed on osimertinib and chemo-immunotherapy were screened; of them, 42 (73.7%) patients had MET GCN <5 and MET/CEP7 < 2 and enrolled the study. Of the 42 patients, 12 are male and 30 are female; the median MET GCN was 3.69, and the median MET/CEP7 was 1.17. The ORR was 78.6% （33/42）, the median PFS was 5.67 months (95%CI: 3.643-7.697), and the OS was not reached. 71.4% (30/42) patients with MET 5>GCN ≥ 3, they had a higher ORR than patients with MEG GCN less than 3, that was 90.0% and 50.0%, respectively. The mPFS was 7.1 months for patients with MET 5>GCN ≥ 3, and was 3.9 months for patients with MET GCN less than 3. The main adverse events were grade II-III edema of lower extremities, it occurred 45.2% (19/42), and it could be attenuated by savolitinib dose reduction. No patient discontinued osimertinib plus savolitinib treatment induced by AE. Conclusions: Osimertinib plus savolitinib had promising results in patients of non-small cell lung cancer with low MET GCN after osimertinib resistance. The MET GCN threshold for MET TKI treatment of osimertinib resistant NSCLC should be set to 3 to benefit most osimertinib resistant patients; and it needs to be validated in the large cohort study. Clinical trial information: NCT07322783 . Clinicopathological features and patient characteristics. Factors No. of patients (n=42) (%) Gender Male 12(28.6) Female 30 (71.4) Median Age (year) 59 MET GCN (median) 3.69 <3 12 (28.6) ≥3 30 (71.4) MET/CEP7 (median) 1.17 ORRmPFS (months) 33 (78.6)5.67 ECOG PS 0 6 (14.3) 12 19 (45.2) 17 (40.5) EGFR Mutations 19 del 26 (61.9) L858R 16 (38.1) Metastatic Patterns Lymph node 13 (31.0) Lung 33 (78.6) Brain 5 (11.9) Others 29 (69.0)

Early-onset gastrointestinal cancers: Rural-urban divide and cancer-site disparities in outcomes.

e23203 Background: Early-onset gastrointestinal (eoGI) cancers, defined as diagnoses occurring before age 50, represent a growing public health concern in the United States (US). While incidence rates of several eoGI malignancies (most notably colorectal cancer) have risen over recent decades, population-level mortality trends remain less clearly characterized. We therefore examined national trends in age-adjusted mortality from eoGI cancers in the US, with a focus on cancer site-specific, geographic, and urban–rural differences. Methods: We retrieved the mortality data from the CDC WONDER underlying causes of death database (years: 1999–2020) for the population aged 18-49 with “Neoplasms of digestive organs” (ICD-10 C15-26) listed as “underlying cause of death”. We analyzed age-adjusted mortality rates (AAMRs) per 100,000 population and assessed temporal trends in the average annual percent change (AAPC) of AAMRs. AAPC and 95% CIs were estimated using the NCI Joinpoint regression program 5.4.0. with the log-scale AAMRs as the dependent variable and year as a continuous covariate, and a p-value < 0.05 considered statistically significant. Subgroup analyses were performed by cancer site, U.S. Census geographic division, and level of urbanization based on the National Center for Health Statistics 2013 Classification. Results: A total of 180,512 eoGI cancer–related deaths were identified. Overall, AAMRs declined, with an AAPC of −0.25% (95% CI, −0.34 to −0.16; p < 0.05). However, trends varied substantially by cancer site. Early-onset colorectal cancer demonstrated a significant increase in mortality (AAPC, 0.56%; 95% CI, 0.30–0.91; p < 0.001). Urban–rural analyses revealed rising mortality for eoGI cancers in rural areas (AAPC, 0.30%; 95% CI, 0.04–0.57; p = 0.01), stable trends in small and medium metropolitan areas (AAPC, 0.06%; 95% CI, −0.16 to 0.24; p = 0.24), and a significant decline in large metropolitan areas (AAPC, −0.46%; 95% CI, −0.84 to −0.08; p = 0.02). By U.S. Census geographic division, mortality declined in the Middle Atlantic (AAPC, −0.57%; p < 0.01) and South Atlantic (AAPC, −0.54%; p < 0.01), whereas mortality increased in the West North Central division (AAPC, 0.34%; p = 0.03). Conclusions: Despite an overall decline in age-adjusted mortality from eoGI cancers in the US, this improvement was not uniform across cancer sites or regions. Early-onset colorectal cancer continues to demonstrate a consistent rise in mortality, particularly in rural areas and select geographic divisions, highlighting persistent and emerging disparities. These findings underscore the need for targeted public health strategies that aim to improve and ensure equitable access to screening and high-quality cancer care. Population Group(1999-2020) AAPC (%) 95% CI (Lower) 95% CI (Upper) P-value Large metropolitan −0.46 −0.84 −0.08 0.01 Small/medium metropolitan 0.06 −0.12 0.25 0.45 Rural 0.31 0.04 0.58 0.026

Depth and durability of response with TGF-β trapping in recurrent or metastatic (R/M) HPV-negative head and neck squamous cell carcinoma (HNSCC): Long-term results from two expansion cohorts of a phase 1/1b study of ficerafusp alfa plus pembrolizumab.

6040 Background: In HPV-negative HNSCC, TGF-β overexpression creates fibrotic barriers within the tumor microenvironment that limit tumor penetration and drive resistance to anti-EGFR and anti-PD1 therapy. Ficerafusp alfa is the first and only bifunctional EGFR-directed antibody designed to trap TGF-β, enabling tumor penetration of immune cells and driving deep and durable responses for potential overall survival (OS) benefit. Methods: Two dose-expansion cohorts of an ongoing phase 1/1b study (NCT04429542) enrolled adults with 1L R/M HNSCC with PD-L1 CPS ≥1. Patients received ficerafusp alfa 750 or 1500 mg IV on D1, 8, and 15 plus pembrolizumab (pembro) 200 mg IV Q3W. Assessments included objective response rate (ORR), duration of response (DOR), and progression free survival (PFS) per RECIST v1.1; OS; safety; and pharmacodynamic (PD) and pharmacokinetic analyses. This is the first report of long-term efficacy follow-up across two cohorts of ficerafusp alfa. Results: As of December 16, 2025, 61 HPV-neg pts were treated in two cohorts (750 mg, n=31; 1500 mg, n=30); 58 pts were efficacy evaluable. Exposure increased in an approximately dose-proportional manner with manageable safety observed in both cohorts. A higher proportion of pts had exposure levels associated with meaningful efficacy with 1500 mg vs 750 mg dosing. Improved outcomes were observed in the 1500 mg vs 750 mg cohort, including deep responses (≥80% tumor shrinkage in 80% vs 47% of responders) and mPFS (9.9 mo vs 6.9 mo), along with increased markers of TGF-β inhibition and tumor penetration in paired biopsies, and increased pro-inflammatory cytokines in blood (Table). Conclusions: Deeper and more durable tumor responses were observed with ficerafusp alfa 1500 mg vs 750 mg. Exposure and PD markers of TGF-β inhibition demonstrated dose-related trends consistent with mechanism of action. Together, these data suggest that TGF-β inhibition with ficerafusp alfa facilitates T-cell infiltration, enhancing immunologic activity, contributing to deep and durable responses for patients with HPV-neg HNSCC. These findings support the rationale for FORTIFI-HN01, an ongoing phase 2/3 trial evaluating this combination in 1L PD-L1 pos, HPV-neg, R/M HNSCC (NCT06788990). Clinical trial information: NCT04429542 . Endpoint (efficacy set) Ficerafusp alfa750 mg + pembroN=30 Ficerafusp alfa1500 mg + pembroN=28 Confirmed ORR/complete response rate, n (%) 17 (57)/4 (13) 15 (54)/6 (21) Responders with ≥80% shrinkage, n (%) 8/17 (47) 12/15 (80) Median DOR, mo NR 21.7 Proportion of responses >12 mo, n (%) 9/17 (53) 9/15 (60) Median PFS, mo 6.9 9.9 Median OS, mo NR 21.3 Tumor TGF-β inhibition: mean change from baseline in pSMAD2, % −16.4 (n=5) −33.2 (n=7) Immune activation: mean change from baseline in blood TNF-α/IFN-γ, % 25.6/163, (n=24) 64.9/346 (n=20)

Early detection of kidney cancer using blood-based multi-gene mRNA profiling in a prospective clinical study.

4542 Background: Kidney cancer remains one of the most aggressive and lethal urological malignancies, largely due to late-stage diagnosis and reliance on invasive tissue biopsies. To address this unmet clinical need, we developed and clinically validated the blood-based, cell-free mRNA test. By quantifying circulating tumor-derived transcripts in plasma, this assay provides rapid and precise molecular insights, supporting precision screening, early diagnosis, prognostication, and treatment monitoring. Methods: In this prospective clinical study, we evaluated real-time expression levels of 30 kidney cancer–associated genes in plasma samples from 51 subjects, including 41 patients with suspected kidney cancer and 10 healthy controls. The primary objective was to assess the diagnostic and prognostic performance of the Geneverify multi-gene blood-based expression panel. Log₂ fold-change values for individual genes were calculated relative to healthy controls and integrated to generate a composite risk score for each subject. Geneverify scores were compared with biopsy-confirmed diagnoses to assess assay sensitivity. Additional statistical analyses evaluated correlations between Geneverify scores and tumor stage, pathological grade, and treatment status. Results: All biopsy-confirmed kidney cancer cases demonstrated Geneverify scores greater than 10. Using an optimized cutoff score of 10, the assay achieved 100% sensitivity for cancer detection. While healthy controls served as the baseline reference, specificity against benign or non-malignant kidney disease could not be fully assessed due to the absence of such cases in this cohort. The majority of patients had early-stage (T1a) kidney cancer. Geneverify scores showed strong correlations with tumor stage, pathological grade, and clinical status. In patients with advanced or metastatic disease undergoing systemic therapy, Geneverify scores declined significantly over time, indicating potential utility for real-time treatment response monitoring. Conclusions: This study represents the first real-time clinical validation of a blood-based, cell-free mRNA genomic assay for kidney cancer detection. The Geneverify test demonstrated excellent diagnostic sensitivity, strong concordance with biopsy-confirmed disease, and meaningful prognostic and treatment-monitoring capabilities. These findings establish Geneverify as a powerful non-invasive alternative to tissue biopsy (based on published data 20% biopsies are false negative) for early detection and precision management of kidney cancer, with the potential to reduce invasive procedures and accelerate personalized oncology care.

A phase 3 study of revumenib in combination with intensive chemotherapy in patients with newly diagnosed <i>NPM1</i> -mutated acute myeloid leukemia (REVEAL-ND NPM1).

TPS6602 Background: There are currently no approved targeted therapies for newly diagnosed (ND) acute myeloid leukemia (AML) harboring a nucleophosmin-1 mutation ( NPM1 m), which occurs in ~30% of ND adult AML cases. In NPM1 m AML, the NPM1m/XPO1 protein complex binds to DNA to sustain the interaction of menin and wild-type KMT2A that drives upregulation of HOX / MEIS gene expression, resulting in hematopoietic differentiation arrest and leukemogenesis. Revumenib is a first-in-class, oral, potent, and selective inhibitor of the menin-KMT2A interaction. In the phase 1/2 AUGMENT-101 study (NCT04065399), revumenib monotherapy demonstrated clinically meaningful response rates and was generally well tolerated in relapsed/refractory NPM1 m AML, leading to US Food and Drug Administration approval for that patient population on October 24, 2025. Standard AML treatment for younger, non-frail adults is based on intensive chemotherapy (IC) regimens and hematopoietic stem cell transplant (HSCT). The addition of revumenib to standard IC may further improve treatment responses specifically in the ND setting. This study is designed to assess the safety and efficacy of revumenib in combination with IC in patients with ND NPM1 m AML. Methods: REVEAL-ND NPM1 is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial (NCT07211958). Eligible patients are ≥12 years of age, weigh ≥40 kg, and have treatment-naive ND AML with locally determined (centrally confirmed) NPM1 m. Patients will be randomized 1:1 to revumenib or placebo in combination with IC. Induction consists of 1 to 2 cycles of revumenib or placebo (dosed orally) alongside IC with cytarabine and daunorubicin or idarubicin (dosed intravenously). Consolidation consists of 1 to 3 cycles of revumenib or placebo plus cytarabine. HSCT may be performed after initial induction or consolidation. Treatment with revumenib or placebo monotherapy will continue for up to 2 years, with long-term follow-up until death, withdrawal of consent, or study closure. The dual primary endpoints are event-free survival and measurable residual disease-negative complete remission (CR) in the bone marrow, both assessed by independent reviewers. A key secondary endpoint is overall survival. Additional investigator-assessed endpoints include CR rate, composite complete remission (CRc) rate, overall response rate, duration of response (CR, CRc), safety, and quality of life. Overall, ~468 patients will be enrolled. As of January 27, 2026, the study is open to enrollment. Clinical trial information: NCT07211958 .

HPV vaccination initiation and completion among sexual minority women in California.

e22573 Background: Human papillomavirus (HPV) is the most common sexually transmitted infection and a known cause of cervical cancer globally. Despite this, vaccination coverage remains below national targets in the United States. Sexual minority women (SMW), those who identify as lesbian, bisexual, or other non-heterosexual orientations, face distinct barriers to accessing preventative healthcare. Patient and provider misconceptions about HPV risk, provider bias, and SMW intersecting identities influence how they navigate the healthcare system. California has the largest LGBTQ+ population in the United States, yet the absence of California-specific data on HPV vaccination represents a critical gap in public health. This database study aimed to examine HPV vaccination initiation and completion among SMW in California to identify and close gaps in the literature. We hypothesize that SMW would have lower HPV vaccination initiation and completion compared to their heterosexual counterparts. Methods: Using data from the 2016 Behavioral Risk Factor Surveillance System (BRFSS), we examined HPV vaccination rates among SMW in California. The analysis was done using R. Based on the 2016 codebook, survey respondents who were coded from California, answered female under "Respondents Sex," and answered either "straight," "lesbian or gay," "bisexual," or "other" sexual orientation/gender identity were included in the analysis. In this context, sexual minority women were defined as either lesbian or gay, bisexual, and/or other given the limitations of the survey. Respondents' ages are aggregated into 5-year blocks; therefore, the respondents analyzed were aged 18 to 49, to include those aged 45. Weighted percentages and 95% confidence intervals were estimated using BRFSS design variables to account for the complex sampling design. Results: 2289 females met the criteria filters above, of whom 2160 identified as straight and 129 as SMW. Of these, 1593 straight women and 95 SMW had missing data on their HPV vaccination status. Therefore, 567 straight women and 34 SMW were included in the vaccination analysis. We found that 26.9% (95% CI 22.0-31.8) of straight women in California initiated HPV vaccination, and 13.0% (95% CI 9.6-16.5) completed HPV vaccination. Compared to straight women, SMW had a lower HPV initiation rate of 21.5% (95% CI 6.0-37.0) and an even lower HPV completion rate of 10.5% (95% CI 0.0-22.1). Conclusions: To our knowledge, this is the first study attempting to characterize and aggregate HPV vaccination data for SMW in California. Similar to national trends, SMW in California had lower HPV initiation and completion rates compared to their heterosexual counterparts. Further, more focused survey questions and research are needed to better inform targeted public health interventions to improve vaccination rates in California, especially among SMW of color.

Preliminary observation of growth and pubertal development following CAR-T cell therapy for children with systemic lupus erythematosus.

e14516 Background: Prolonged glucocorticoid and immunosuppressive therapy in systemic lupus erythematosus (SLE) children can cause a range of unique adverse effects, including impaired linear growth and disrupted pubertal development. Chimeric antigen receptor T-cell (CAR-T) therapy has achieved initial efficacy in the treatment of lupus, potentially allowing for rapid discontinuation of chronic immunosuppression. Studies involving pediatric patients and examining the impact of CAR-T therapy on their growth and developmental outcomes remain scarce. Methods: Pediatric r/r SLE patients ( &gt; age 10 years old) were allowed to enrolled in our clinical trial (NCT06947460), besides monitoring safety (primarily evaluated through dose-limiting toxicity) and the efficacy (SLEDAI, LLDAS, SRI-4) of CAR-T cell therapy for r/r SLE children, improvement of growth and pubertal development was monitored. Baseline height was measured in all patients before CAR-T cell infusion, followed by regular assessments at 3-month intervals post-treatment according to a predefined follow-up plan, assessed by the criteria of the Standard for Height Level Classification among Children and Adolescents Aged 7–18 Years (2018 Version). Pubertal development was also assessed using Tanner staging. Results: Between Jun 12 and Sep 20, 2025, 4 r/r SLE children were enrolled. All patients stopped glucocorticoids and immunosuppressants pre-infusion and remained drug-free. No DLTs occurred within 28 days after infusion. All patients experienced grade 1 CRS; 25% had grade 2 hematologic toxicity. No neurotoxicity was observed and all toxicities resolved with supportive care. As of 31 December 2025, all 4 patients completed efficacy assessments at months 1, 3, and 6. Remission rates were 75%/75%/75% (DORIS), 75%/100%/75% (LLDAS), and 75%/75%/75% (SRI-4). 1 patient had a grade 3 viral infection and fully recovered after hospitalization. SLEDAI and PGA scores decreased by 2–6 and 0.5–2 points, respectively. From drug discontinuation to 6 months after CAR-T infusion, all patients demonstrated catch-up growth. Compared with references, a part of patients exhibited reduced height prior to treatment discontinuation: the 12-year-old girl (144cm) was approximately 3cm below the expected height (147cm), and the 11-year-old girl (133cm) was about 1cm below the expected height (134cm). The remaining patients had heights within the normal range. Height gains ranged from +1cm to +20.5cm. All patients exhibited secondary sexual characteristics within normal Tanner stages, indicating no missed pubertal window. Conclusions: CAR-T cell therapy shows a favorable safety and efficacy profile for r/r SLE children. These data suggest it may mitigate growth and development toxicity associated with conventional immunosuppressive therapy, which is unique unmet need for pediatric SLE patients. Clinical trial information: NCT06947460 .

EMBARK: Testosterone recovery to &gt;250 ng/dL following treatment suspension.

5088 Background: The phase 3 EMBARK trial demonstrated significantly longer metastasis-free survival and overall survival for enzalutamide plus leuprolide (enzalutamide combination) vs leuprolide alone in patients with prostate cancer and high-risk biochemical recurrence (hrBCR). In EMBARK, patients with prostate-specific antigen (PSA) &lt; 0.2 ng/mL at week 36 suspended treatment at week 37. Androgen deprivation-related testosterone suppression has been linked to adverse health outcomes, whereas testosterone recovery while off treatment has been associated with improved quality of life. The objective of this post hoc analysis was to assess testosterone recovery to &gt; 250 ng/dL during treatment suspension in patients treated with enzalutamide combination. Methods: Eligible patients had hrBCR, with a PSA doubling time of ≤9 months. Patients were randomized 1:1:1 to enzalutamide + leuprolide, leuprolide alone, or enzalutamide monotherapy. Patients who suspended treatment at week 37 reinitiated treatment upon PSA increase to protocol-defined levels. Testosterone levels were assessed every 12 weeks. Results: In the enzalutamide combination group, 320 patients suspended treatment. During treatment suspension, testosterone recovery to &gt; 250 ng/dL occurred in 108 patients (33.8%) (Table). Among those who recovered their testosterone, median and mean time to recovery was 5.6 months and 6.8 months, respectively, although some patients had delayed recovery (Table). Conclusions: Testosterone recovery to &gt; 250 ng/dL during treatment suspension was observed in approximately one-third of patients treated with enzalutamide combination. While average time to testosterone recovery among those who recovered was ~6 months, recovery was delayed in some patients. Disclosure: Pfizer’s generative AI tool MAIA was used in developing this abstract; the authors reviewed, edited, and take full responsibility for the content. Clinical trial information: NCT02319837 . Enza combination(N=320) Patients who reached testosterone recovery, n (%) 108 (33.8) Time to testosterone recovery &gt;250 ng/dL, months † Median (range) 5.6 (0.0–22.1) Mean (SD) 6.8 (2.87) The data cutoff date was January 31, 2023. † Time to testosterone recovery during treatment suspension is based on the number of patients who reached testosterone recovery, and was defined as the time from the date of the start of treatment suspension to the date of the first occurrence of testosterone &gt;250 ng/dL. The summary is based on testosterone records during treatment suspension from patients who had treatment suspension and non-missing testosterone records after treatment suspension. For patients who reinitiated treatment, testosterone records after reinitiation were not considered.

Contemporary outcomes and treatment patterns in neuroendocrine carcinoma of the breast: A population-based SEER analysis.

e12758 Background: Neuroendocrine carcinoma of the breast (NECB) is a rare malignancy accounting for &lt; 0.5% of breast cancers, with limited contemporary population-level data describing outcomes. Prior studies were constrained by small sample sizes, heterogeneous histologic definitions, and earlier treatment eras. We performed a population-based analysis using the SEER 21 Registries database to characterize clinicopathologic features, treatment utilization, and overall survival (OS) in NECB. Methods: We conducted a retrospective cohort study of patients diagnosed with NECB between 2000 and 2021 using Surveillance, Epidemiology, and End Results (SEER) 21 Registries, Research Plus database (N = 901). NECB was identified using predefined ICD-O-3 histology codes for neuroendocrine neoplasms of the breast. Demographics, race/ethnicity, Combined Summary Stage (2004+), and receipt of surgery, radiation, and chemotherapy were summarized descriptively. Given low individual frequencies, histologic subtypes were analyzed collectively. OS was estimated using Kaplan–Meier methods overall and stratified by stage at diagnosis. Analyses of hormone receptor subtype were restricted to cases diagnosed in 2010–2021, reflecting availability of contemporary biomarker data. Results: Among 901 patients, 98.3% were female. Race/ethnicity distribution was 69.7% non-Hispanic White, 13.0% Hispanic, 12.4% non-Hispanic Black, 4.6% non-Hispanic Asian/Pacific Islander, and 0.3% non-Hispanic American Indian/Alaska Native. Among staged cases (n = 760), disease was localized in 47.1%, regional in 26.1%, distant in 22.8%, and in situ in 4.1%. Treatment included surgery in 64.8%, radiation in 56.6%, and chemotherapy in 32.1%. Overall, 53.5% experienced death events. Median OS for the cohort was 9.0 years, with 5- and 10-year OS rates of 59.5% and 45.2%, respectively. Stage-stratified median OS was 15.0 years for localized disease, 8.0 years for regional disease, and 2.0 years for distant disease, with corresponding 5-year OS rates of 74.3%, 61.4%, and 22.2%. Among cases diagnosed in 2010 or later with available subtype data (n = 360), tumors were predominantly hormone receptor–positive/HER2-negative (74.2%), followed by triple-negative disease (22.2%). Conclusions: In this large SEER 21 Registries cohort, NECB demonstrated substantial mortality with survival strongly dependent on stage at diagnosis. Despite multimodality treatment, advanced-stage disease remained associated with poor outcomes. These findings provide contemporary national survival benchmarks for NECB and highlight the need for NECB-specific clinical investigation and risk-stratified therapeutic strategies.

Circulating tumor DNA to add prognostic stratification beyond CA-125 in epithelial ovarian cancer.

5562 Background: Ovarian cancer has a high risk of recurrence, particularly in patients with advanced-stage disease. CA-125 is routinely used to assess disease burden and recurrence risk but has limited prognostic accuracy. Circulating tumor DNA (ctDNA) has emerged as a potential biomarker that may better reflect tumor biology and enable earlier identification of recurrence. Methods: Patients with epithelial ovarian cancer and available plasma ctDNA and CA-125 measurements collected in association with surgical debulking were included. CA-125 was stratified using a standard clinical cutoff of 35 U/mL. Average cfDNA yield (ng/mL) was stratified into high and low ctDNA groups based on the cohort median. Associations were assessed using correlation and categorical analyses. Overall survival (OS) was evaluated using Kaplan–Meier methods and Cox proportional hazards models, including multivariable analyses. Results: Among 89 patients, ctDNA concentration was positively associated with CA-125 (Spearman ρ = 0.25; p = 0.017). Patients with high CA-125 had higher ctDNA levels than those with low CA-125 (mean 21.2 vs 7.6; p = 0.0044). High ctDNA concentration was associated with worse OS compared with low ctDNA (log-rank p = 0.0036; HR 3.48, 95% CI 1.50–8.06), with median OS (mOS) of 1386 days versus not reached. Patients with both high CA-125 and high ctDNA experienced markedly worse mOS than patients with low ctDNA (log-rank p = 0.0045; HR 3.48, 95% CI 1.47–8.21), with a mOS of 827 days versus not reached respectively. This added stratification by ctDNA persisted across multiple sensitivity analyses, including stratification by timing of sample collection relative to surgery, with consistent prognostic associations observed in pre-surgery samples (mOS 953 days; log-rank p = 0.031) and post-surgery samples (mOS 569 days; log-rank p = 0.045), as well as in analyses of high-grade serous ovarian cancer, advanced-stage disease, and neoadjuvant therapy. In multivariable Cox regression adjusting for CA-125, disease stage, surgical status, and neoadjuvant therapy, ctDNA remained independently associated with OS (HR 1.012, 95% CI 1.003–1.019). Conclusions: ctDNA consistently added prognostic value beyond CA-125 despite treatment-related heterogeneity, suggesting that ctDNA concentration captures biologic features of tumor behavior not reflected by CA-125 alone. Importantly, ctDNA remained predictive regardless of the timing of sample collection. These findings support ctDNA as a complementary biomarker for baseline prognostic stratification.

Trends over 18 months in the utilization of ctDNA monitoring assays for solid tumor patients in US clinical practice.

e23135 Background: Circulating tumor DNA (ctDNA) monitoring assays are increasingly incorporated into treatment planning, yet optimal patient selection and clinical utility across stages remain under evaluation. This study assessed oncologist awareness, adoption patterns, decision drivers and perceptions related to ctDNA monitoring in solid tumors. Methods: Three online surveys of 150 oncologists were conducted in April 2024, October 2024, and April 2025. Respondents reported retrospective use of ctDNA monitoring for early- and late-stage NSCLC, breast, colorectal, prostate, and bladder cancers. Analyses examined overall and segment-level trends by practice setting, experience, region, preferred assay, and patient caseload. A sum-of-ranks method quantified assay selection drivers. Results: Across all waves, oncologists reported ordering similar numbers of ctDNA monitoring tests for early- and late-stage patients. Testing volume was highest in NSCLC (4–6 tests/month), colorectal cancer (5 tests/month), and breast cancer (5–6 tests/month). Respondents anticipated increasing use by 4–5 tests within one year and 5–6 within two years. Clinical performance consistently ranked as a primary assay selection factor (W1: 347; W3: 367), while supporting clinical data was most influential in Wave 2 (377). Quantitative ctDNA availability and report clarity increased in importance, whereas KOL recommendations declined. Physicians report a positive attitude towards ctDNA cancer monitoring, with 81% (95% CI 75–87) agreeing that “The use of ctDNA cancer monitoring really excites me.” Many express interest in increasing their knowledge of ctDNA cancer monitoring (74%, 95% CI 67–817) and believe that ctDNA monitoring brings comfort and reassurance for their patients (71%, 95% CI 64–78). However, physicians are split in their preference between tissue-informed and tissue-naïve ctDNA approaches, with 57% (95% CI 49–65) agreeing more with “I believe tissue-informed ctDNA assays are better,” while 40% (95% CI 32–48) agree more with “I believe tissue-naïve ctDNA assays are better.” Conclusions: Oncologists demonstrate sustained and growing interest in ctDNA monitoring to guide patient management, with expected increases in utilization. Despite adoption, many clinicians continue to seek clarity on optimal use and the impact of ctDNA monitoring on patient outcomes. Agreement with statements on ctDNA cancer monitoring. Statements Agree (6-7), % of respondents (N=150) 95% CI (%) Complements other monitoring approaches 80% 74%-86% Would like to know more 68% 61%-76% Would like to do more ctDNA monitoring 64% 56%-72% Provides objective insights 68% 61%-76% More informed treatment decisions 60% 52%-68% Others think highly of 49% 41%-47% Able to effectively interpret and act on results 54% 46%-62% Better than other monitoring approaches 42% 34%-50% Could replace scans 36% 28%-44%

Efficacy and safety of venetoclax-based regimens in chronic myelomonocytic leukemia: A systematic review and meta-analysis.

e18593 Background: Chronic myelomonocytic leukemia (CMML) is a heterogeneous myelodysplastic/myeloproliferative neoplasm with limited disease-modifying options beyond hypomethylating agents (HMAs) and allogeneic stem cell transplantation. Venetoclax (VEN), a selective BCL-2 inhibitor, is increasingly used off-label in CMML; however, CMML-specific efficacy and safety data remain fragmented and heterogeneous. We conducted a systematic review and meta-analysis to define clinical outcomes associated with VEN-based therapy in CMML. Methods: A systematic search of PubMed, Embase, and Cochrane CENTRAL from inception through August 2025 was performed in accordance with PRISMA 2020 guidelines. Adult CMML cohorts (≥5 patients) treated with VEN-based regimens and reporting CMML-specific outcomes were included. Random-effects meta-analyses of proportions were conducted for complete remission (CR), marrow complete remission (mCR), and overall response rate (ORR). Heterogeneity was assessed using the I² statistic. Results: Seventeen publications representing nine unique studies were included, encompassing 145 VEN-treated CMML patients. Most regimens combined VEN with azacitidine, decitabine, or oral decitabine–cedazuridine. Responses typically occurred early (within 1–2 cycles), but durability was limited. Pooled response estimates were: CR 19.1% (95% CI, 9.4–34.9; I²=55%), mCR 36.4% (95% CI, 24.7–50.0; I²=21%), and ORR 71.9% (95% CI, 56.5–83.4; I²=56%). Survival outcomes were modest, with median overall survival generally ranging from 10–16 months across real-world cohorts. VEN-based therapy was associated with substantial myelosuppression, including frequent grade ≥3 neutropenia and thrombocytopenia, with clinically significant infectious complications; early mortality remained low. Patients without RAS-pathway mutations and those treated in the frontline or transplant-directed setting appeared to derive greater benefit. Conclusions: VEN-based regimens demonstrate measurable but limited activity in CMML, characterized by high overall response rates but low complete remission rates and modest durability. These findings support a selective role for VEN as treatment intensification or as a bridge to transplantation rather than routine therapy. Prospective CMML-specific trials are needed to define optimal patient selection and therapeutic positioning.

Prognostic value and role in guiding individualized treatment of imaging extranodal extension (iENE) in nasopharyngeal carcinoma.

6078 Background: Imaging extranodal extension (iENE) is a critical prognostic factor in nasopharyngeal carcinoma (NPC). While international consensus has standardized iENE grading, its prognostic value in NPC remains to be validated. Furthermore, evidence is lacking regarding the utility of iENE-based risk stratification in guiding individualized treatment, particularly for identifying candidates benefiting from adjuvant chemotherapy (AC). Methods: A total of 694 non-metastatic NPC patients with cervical lymph node metastasis who received intensity-modulated radiotherapy (IMRT) at Sun Yat-sen University Cancer Center from 2016 to 2017 were included. iENE was graded based on international group consensus by two radiologists through a consensus reading protocol: G0 (no extranodal extension), G1 (infiltration of perinodal fat), G2 (matted nodes), and G3 (invasion of adjacent structures including muscles and neurovascular bundles). Progression-free survival and overall survival were analyzed using the Kaplan–Meier method and log-rank test. Multivariable Cox proportional hazards models were applied to adjust for confounders. Time-dependent receiver operating characteristic (TD-ROC) curve analysis was used to evaluate the predictive performance of clinical variables. Stratified analysis for prognosis was performed based on treatment strategies including concurrent chemoradiotherapy(CCRT), induction chemotherapy plus CCRT(IC+CCRT), and IC+CCRT followed by adjuvant chemotherapy (IC+CCRT+AC). Results: The cohort included 257 (37.0%) G0, 117 (16.9%) G1, 216 (31.1%) G2, and 104 (15.0%) G3 patients. Survival analysis for OS, PFS, DMFS, and LRRFS revealed that G1 patients showed a comparable prognosis to G0 patients(5-year PFS: 82.1% vs. 89.1%, P &gt; 0.05), whereas G2 and G3 patients exhibited significantly worse outcomes; therefore, G0 and G1 were combined into a low-risk subgroup. Multivariable analysis adjusting for T stage, N stage, volume of maximal lymph node, clinical stage, and treatment regimens confirmed that the refined iENE grading was an independent prognostic factor for PFS (G2 vs. G0/1: HR 1.77, 95% CI 1.25–2.51, P = 0.001; G3 vs. G0/1: HR 1.90, 95% CI 1.08–3.36, P = 0.027). TD-ROC curve demonstrated that the predictive performance of iENE for 1-, 3-, and 5-year PFS and OS was superior to that of T stage and pre-treatment EBV DNA. Most importantly, subgroup analysis indicated that the addition of AC significantly improved PFS outcomes in the G2/G3 subgroup (P = 0.006 and P = 0.009, respectively), whereas no survival benefit was observed in the low-risk G0/G1 subgroup (P = 0.133). Conclusions: The refined iENE grading system provides robust risk stratification for NPC. This system outperforms traditional biomarkers like EBV DNA, better distinguishing prognostic outcomes in patients and effectively guiding the application of intensified treatment.