Browse Articles

A phase 2/3 study of EIK1001 in combination with pembrolizumab and chemotherapy in participants with stage 4 non–small cell lung cancer (NSCLC) (TeLuRide-008).

TPS8668 Background: Immune checkpoint inhibitors (ICIs) reverse tumor-induced immune suppression and promote effective anti-tumor T-cell responses. Current standard of care (SOC) for Stage 4 NSCLC combining ICIs (e.g. pembrolizumab [pembro]) plus histology-appropriate chemotherapy (chemo) confers significant clinical benefit over chemo alone, yet many patients progress nonetheless, highlighting a large unmet medical need in this disease. EIK1001, a Toll-like receptor (TLR) 7/8 dual agonist, activates myeloid and plasmacytoid dendritic cells stimulating innate and adaptive immunity. In completed Phase 1 and ongoing Phase 2 studies, EIK1001 exhibits a manageable safety profile and encouraging anti-tumor activity both as monotherapy and in combination with ICIs. Methods: TeLuRide-008 (NCT#07365319) is a global, multicenter, randomized, double-blind, placebo-controlled, adaptive Phase 2/3 study of EIK1001 or placebo, in combination with pembro and histology-appropriate chemo in systemic-therapy-naïve pts with stage 4 NSCLC. In Phase 2, pts are randomized 1:1:1 to receive 1 of 2 doses of EIK1001 or placebo, + pembro and chemo (Part 1:Dose optimization; n~120), followed by additional enrollment with 1:1 randomization of new pts (n~160), at the EIK1001 selected dose or placebo (Part 2: Dose Expansion; n~280). If the study proceeds to Phase 3 (Part 3: Confirmatory), ongoing Phase 2 pts to continue treatment, and n~440 new pts will be randomized 1:1 to receive the selected dose of EIK1001 or placebo, + pembro and chemo (n = up to 750). Key eligibility criteria: pts ≥ 18 years of age, life expectancy ≥ 3 months, stage 4 NSCLC (NSQ or SQ), no actionable mutations requiring targeted therapy, ≥ 1 measurable lesion per RECIST v1.1, and no history of symptomatic pneumonitis. Primary objectives: evaluate efficacy and safety of 2 doses of EIK1001 + pembro and chemo for dose optimization and compare PFS (RECIST v1.1 by BICR) and OS between the selected EIK1001 dose and placebo, + pembro and chemo. Secondary objectives: safety and tolerability, ORR and DOR per RECIST v1.1 by BICR. Exploratory objectives: time to response, EIK1001 exposure-response relationships, and health-related quality of life. Clinical trial information: NCT#07365319 .

Beyond local mucosal patterns: Vision transformer–based modeling for diagnosis of gastric tumors on endoscopic imaging.

e15515 Background: Gastric cancer remains a leading cause of cancer-related mortality worldwide, largely due to delayed diagnosis and subtle early mucosal changes that challenge visual detection. Upper gastrointestinal endoscopy is the primary diagnostic modality for gastric tumors; however, interpretation is highly operator dependent, with significant interobserver variability, particularly for early-stage lesions and flat or diffuse tumors. Convolutional neural networks (CNNs) have demonstrated promise in automated endoscopic image analysis but rely on localized receptive fields that may inadequately capture global mucosal architecture. Vision Transformers (ViTs) introduce a fundamentally different paradigm by leveraging self-attention to model long-range spatial dependencies across entire images. We evaluated a ViT-B/16 model for gastric tumor classification using curated endoscopic imaging datasets. Methods: We analyzed publicly available gastric endoscopy datasets derived from multiple institutions, including malignant gastric tumors, benign gastric lesions, and non-neoplastic mucosa annotated by expert endoscopists with histopathologic confirmation. Images were standardized, augmented, and split into training and validation cohorts using stratified sampling. A Vision Transformer B/16 model pretrained on ImageNet was fine-tuned for multi-class gastric lesion classification. Input images (224×224) were divided into non-overlapping 16×16 patches and embedded into a token sequence augmented with positional encodings and a learnable class token. The architecture employed 12 transformer encoder blocks with multi-head self-attention and feed-forward layers, enabling global contextual reasoning across mucosal patterns. Performance was assessed using accuracy, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUROC). Results: The Vision Transformer achieved strong diagnostic performance, with overall accuracy exceeding 96% and AUROC greater than 0.96 across gastric lesion categories. Attention-based global modeling improved discrimination of early gastric cancers and lesions with diffuse or irregular mucosal patterns, reducing misclassification commonly observed with convolutional approaches. Performance remained stable across lesion morphology and imaging conditions, supporting generalizability. Conclusions: Vision Transformer–based modeling enables accurate and interpretable diagnosis of gastric tumors by capturing global mucosal and structural context beyond localized feature extraction. While computationally more intensive than CNNs, ViT architectures offer complementary advantages for complex endoscopic imaging tasks and warrant further prospective evaluation to enhance early gastric cancer detection and diagnostic consistency.

Olanzapine for weight gain in children undergoing chemotherapy for solid-organ malignancies: An investigator-initiated, open-label, multicenter, phase III randomized controlled trial (SNOWMAN).

10053 Background: Children receiving intensive chemotherapy for solid-organ malignancies frequently experience deterioration in nutritional status. Olanzapine improves nutritional outcomes in adults with advanced cancer and is guideline-endorsed. Its use in pediatric oncology has been limited by safety concerns and lack of robust data. We conducted this trial to evaluate the efficacy and safety of olanzapine for weight gain in children undergoing chemotherapy for solid-organ malignancies. Methods: In this open-label, investigator-initiated, multicenter, phase III randomized trial (CTRI/2024/03/064371), children aged 2-18 years with newly diagnosed solid-organ malignancies were randomized 1:1 to receive olanzapine (1.25-2.5 mg once daily, weight-based) plus standard dietary counseling (SDC) or SDC alone for 12 weeks, stratified by nutritional status. The primary endpoint was the proportion of participants achieving ≥5% weight gain at 12 weeks. Secondary endpoints included changes in appetite scores (visual analog scale), anorexia-related quality of life (QoL) (Peds-FAACT), anthropometric measures (weight, body-mass index, and mid-upper arm circumference), dietary intake, health-related QoL (PedsQL Cancer Module v3.0), and safety outcomes (CTCAE v5.0). Exploratory endpoints included longitudinal changes in body composition, using air-displacement plethysmography and skeletal muscle mass assessed by computed-tomography derived L3-L4 psoas muscle area. Results: A total of 130 participants were randomized (median age of 11.1 years; 13.9% undernourished), of whom 117 (60 olanzapine plus SDC, 57 SDC) had evaluable outcomes. At 12 weeks, 21/60 (35%) in olanzapine plus SDC and 22/57 (38.6%) in SDC group achieved the primary endpoint, with no significant difference between groups (OR 0.86, 95% CI 0.40-1.82; p=0.69). Longitudinal analyses showed no significant differences between groups in appetite scores, anthropometric measures, dietary intake, and QoL. Exploratory analyses showed no differential impact on skeletal muscle mass or fat proportions. Rates of grade ≥3 adverse events were similar between groups. No extrapyramidal symptoms were observed, and no participant required dose modification or discontinuation of olanzapine due to sedation or QTc prolongation. Conclusions: The addition of olanzapine to SDC does not increase the proportion of children achieving clinically meaningful weight gain over 12 weeks. The impact of pharmacological nutritional modulation may be limited by the physical hurdles posed by highly intensive pediatric chemotherapy protocols. Olanzapine was well tolerated and these data provide reassurance regarding its short-term safety for other supportive care indications in pediatric oncology. Clinical trial information: CTRI/2024/03/064371.

Total neoadjuvant chemotherapy with FLOT for resectable gastric and gastroesophageal junction adenocarcinoma: Real-world outcomes from a Chilean oncology institution.

e15720 Background: Perioperative FLOT improves survival and pathological complete response (pCR) in resectable gastric cancer; however, postoperative chemotherapy completion remains suboptimal due to toxicity. Delivering all 8 cycles of FLOT chemotherapy preoperatively as total neoadjuvant therapy (TNT) may improve adherence and oncologic outcomes. We report safety, pathological response, and survival outcomes from a large Chilean real-world cohort treated with total neoadjuvant chemotherapy FLOT. Methods: We performed a retrospective cohort study of patients with resectable, locally advanced gastric or gastroesophageal junction adenocarcinoma (cT1–4 N+ or cT3–4 N0, M0) treated at Instituto Oncologico Fundacion Arturo Lopez Perez, Santiago, Chile, between May 2019 and December 2024. All patients were planned to receive eight cycles of neoadjuvant FLOT chemotherapy prior to surgery. Clinical, pathological, and treatment-related variables were collected from institutional databases and medical records. Survival outcomes were estimated using the Kaplan–Meier method. Results: Ninety-one patients were included. Mean age was 58 years; 67% were male and 88% had ECOG performance status 0–1. 40.7% were diffusive pattern (signet ring cell). 74.8% patients were cT3-4 and 78% were cN+. The median number of administered FLOT cycles was 8. Grade ≥3 treatment-related adverse events occurred in 21.7%, most commonly gastrointestinal toxicity and neutropenia. Dose reductions were required in 41.8%, and permanent treatment discontinuation occurred in 17.6%. Most patients underwent total gastrectomy (76.9%) with D2 lymphadenectomy (94.5%). R0 resection was achieved in 97.8%. Pathological complete response was observed in 18.7%. 22% and 50.5% achieved ypT0 and ypN0 status respectively. The median follow-up was 43.8 months. 36-month overall survival was 78.2% and disease-free survival was 73.7%. Recurrence occurred in 22%, predominantly at distant sites such as peritoneal and liver metastases. Conclusions: Total neoadjuvant FLOT demonstrated acceptable toxicity, high complete response, R0 resection, and nodal clearance rates, and encouraging long-term survival in a real-world Chilean population. These findings support total neoadjuvant FLOT as a feasible and effective strategy for resectable gastric and gastroesophageal junction adenocarcinoma.

Comparative benchmarking of U.S. oncology populations and survival using a multi-health system EHR data.

e23401 Background: Real-world oncology research relies on electronic health record (EHR) data that are representative of the U.S. cancer population and enable reliable survival estimates. Truveta receives EHR data from U.S. health care systems that are refreshed daily and used for oncology real-world evidence generation. This study benchmarks oncology populations in Truveta Data against the Surveillance, Epidemiology, and End Results (SEER) Program to assess demographic representativeness and concordance of overall survival (OS) estimates across six solid tumor types (bladder, breast, cervical, colorectal, lung, and prostate). Methods: 3.8M patients with a qualifying cancer diagnosis were identified in Truveta Data. Patients included in the study were diagnosed between January 1, 2017 and December 22, 2025 and followed from diagnosis until death or last encounter. Patients included had at least one encounter in the year prior to diagnosis and data characterizing their tumor (stage, grade, or performance status). SEER data were accessed on December 22, 2025. All patients were aged ≥18 years and had one primary tumor. Demographics were summarized using counts and percentages. OS was estimated at prespecified time points (1–5 years) by cancer type and subgroup (age group, sex, and race/ethnicity). Results: The study included 368,774 Truveta patients (bladder n = 10,350; breast n = 143,883; cervical n = 7,023; colorectal n = 42,797; lung n = 100,190; prostate n = 64,531) and 3,563,896 SEER patients. Overall, 58% of Truveta and 55% of SEER patients were aged ≥65 years. Across all cancers, demographic distributions from Truveta were broadly concordant with SEER. The proportion of non-Hispanic White patients was higher in Truveta (63–85%) than in SEER (51–85%), with differences of 4–12% across cancer types. Conversely, the proportion of Hispanic patients was lower in Truveta (3–16%) than in SEER (7–25%), with differences of −3% to −9%. Distributions for other race/ethnicity categories, age groups, and sex differed minimally (≤5 absolute percentage points). Estimated 1-year OS in Truveta was 81% for bladder cancer, 97% for breast, 89% for cervical, 96% for prostate, 86% for colorectal, and 68% for lung. Absolute differences in 1-year OS relative to SEER were ≤2 percentage points for bladder, breast, cervical, and prostate cancers. Truveta estimates were 8% higher for colorectal and 26% higher for lung. Conclusions: OS estimates from Truveta were broadly concordant with SEER across multiple cancer types. Differences varied by cancer type, underscoring the importance of reporting time-specific survival estimates with demographic distributions when interpreting results from real-world and registry-based data sources. These findings support the use of real-world EHR data to examine associations between risk factors, treatment patterns, outcomes, and in-depth longitudinal care of cancer patients.

iPREDICT: Phase II study of CD8 PET in patients with immunoresponsive solid tumors—Imaging characteristics and correlation with RECIST response.

3069 Background: CD8 T cells mediate antitumor effects of immune checkpoint blockade (ICB); their histologically-determined abundance prior to or during therapy (Rx) appears to correlate with ICB response in melanoma (MEL) and other solid tumors. We performed this Phase IIb study to assess CD8 targeted PET imaging with 89 Zr-crefmirlimab berdoxam prior to and during ICB Rx to study its potential as a marker for Rx selection, enhancement or even replacement of existing tumor measurement systems, and correlation of clinical outcomes. Methods: 70 patients (pts) with MEL or Merkel cell cancer (MCC) (27), renal cell cancer (RCC) (35) or lung cancer (NSCLC) (8) who were eligible for first or second-line single- or double-agent ICB or ICB plus an oral kinase inhibitor (TKI) were enrolled. 89 Zr-crefmirlimab berdoxam (1 mCi,1.5 mg protein), was administered intravenously ≤2 weeks prior to cycle 1 of ICB Rx, followed by a PET/CT scan 24 (+/-3) hours later (baseline, BL). The 2nd tracer injection and associated PET/CT scan occurred 4-6 weeks after ICB Rx initiation, prior to cycle 3 (on treatment, OT). Standard of Care imaging and RECIST 1.1 were used to assess response to Rx. Results: All 70 pts were evaluable for safety analysis; none experienced an SAE related to imaging agent. 65 pts (21 MEL, 2 MCC, 34 RCC and 8 NSCLC) were included in the primary endpoint analysis of correlating CD8 PET scans with best confirmed overall response (BOR) by RECIST 1.1. MEL and MCC pts received single (6/23) or double ICB (17/23), RCC pts received single ICB with/without TKI (21/34) or dual ICB (13/34), and all NSLCL pts received single ICB. In the RCC cohort, multiple CD8 PET metrics showed statistically significant association with either individual BOR or Binary Response at BL, OT or as delta, including: Tumor Standard Uptake Value (SUV), Lymph Node (LN) SUV, relative percentage of CD8 negative or positive lesions and normal organ SUV. Normalization to reference organs improved the correlation with BOR for the combined cohorts and for the MEL/MCC cohort. Depending on clinical objectives, different classification rules to predict BOR were applied, prioritizing specificity for non-responders and sensitivity for responders (Table). These results were cohort-dependent, as each cohort exhibited a distinct distribution of SUVs. Conclusions: PET imaging can quantitate CD8 T cells with sufficient specificity and sensitivity to support further study in selection of pts for Rx regimens and assessing early response to therapy. Clinical trial information: NCT05013099 . Prediction of BOR by CD8 PET. Cohort Response Parameter Timepoint AUC 95% CI Sensitivity Specificity MEL + MCC CR+PR vs SD+PD Spleen SUVmean BL 0.67 0.44,0.90 87.5 60.0 MEL + MCC CR+PR vs SD+PD Tumor SUVmax normal. to thyroid Delta 0.70 0.46, 0.95 85.7 64.3 RCC CR+PR vs SD+PD Hottest LN SUVmax OT 0.84 0.65, 1.00 71.4 90.9 RCC CR vs PR+SD+PD % CD8 negative lesions Delta 0.96 0.87, 1.00 100.0 92.3

Real-world retrospective analysis of outcomes, treatment duration, dose intensity, and safety of enfortumab vedotin with or without pembrolizumab in urothelial carcinoma.

e16580 Background: Enfortumab vedotin (EV) in combination with pembrolizumab (P) has been FDA-approved for patients with locally advanced or metastatic urothelial carcinoma (la/mUC), based on the EV-302 trial, which demonstrated superior survival outcomes compared to traditional chemotherapy. This study aims to evaluate real-world treatment outcomes, duration, dose intensity (DI), and safety profiles of EV with or without P. Methods: We conducted a retrospective, single-center study involving patients with urothelial carcinoma who received EV ± P at the Medical University of South Carolina from January 1, 2019, to August 31, 2025. Treatment duration was defined as the interval from the first dose of EV to 14 days post-last dose or December 31, 2025, whichever occurred first. DI (mg/kg/week) was calculated as the total dose of EV divided by treatment duration. Cox proportional hazards models were used to examine the associations between DI, progression-free survival (PFS), and overall survival (OS). Results: Of 78 patients included, 58% (n = 45) received EV+P concurrently. The concurrent (EV+P) group demonstrated a median OS of 22.4 months (95% CI, 15-NR) and PFS of 9.1 months (95% CI, 5.0-14.7), compared to 12.2 months (95% CI, 9.1-17.0) and 4.4 months (95% CI, 2.8-8.3) in the EV-monotherapy group. Notably, 50% of the total cohort required dose reductions. Discontinuation rates were high in both the concurrent (91%) and monotherapy (97%) groups, but primary drivers differed: in the EV+P group, treatment-related toxicities were the leading cause of discontinuation (59% vs. 27% for disease progression), predominanly neuropathy (24%), whereas disease progression was the primary cause in the monotherapy group (53% vs. 25% for toxicities). Median treatment duration was 4.2 months for both groups. Median DI was lower in the concurrent group (0.63 mg/kg/week) than in the monotherapy group (0.70 mg/kg/week), both of which fell short of the trial-standard DI of 0.83 and 0.94 mg/kg/week. For patients receiving 3 or more doses of EV who discontinued due to toxicities, lower DI was significantly associated with better PFS (p < 0.05) after adjusting for age, gender, performance status, and comorbidities, though it did not significantly impact OS. Conclusions: Real-world EV+P outcomes in this population are more modest than trial results, characterized by prevalent toxicity-related treatment discontinuation. The association between lower DI and longer PFS may be explained by the fact that patients with extended treatment duration naturally require more dose modifications to manage side effects. Because OS was not significantly affected by DI in this study, practitioners may consider judicious dose adjustments to help maintain a balance between clinical efficacy and treatment-limiting toxicity.

Targeting ALKBH5 with mefloquine as a therapeutic strategy to enhance antitumor immunity in osteosarcoma.

e14596 Background: Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, with a second incidence peak in older adults. Most treatments require intensive chemotherapy and surgery, with outcomes for patients with metastatic or relapsed disease remain poor, with five-year survival rates below 30%. Approximately 20% of patients present with metastatic disease at diagnosis, underscoring the urgent need for novel, clinically actionable therapeutic strategies. We recently identified the RNA demethylase ALKBH5 as a key driver of OS growth, metastasis, and immune evasion. Through high-throughput screening of FDA-approved compounds, we identified mefloquine as a small-molecule inhibitor of ALKBH5, with potential to enhance antitumor immune responses and improve immunotherapy efficacy in OS. Methods: Depletion of ALKBH5 was achieved using shRNA and CRISPR-Cas9 approaches to evaluate its role in OS growth and metastasis. Fluorescence-based high-throughput screening of FDA-approved and LOPAC libraries identified mefloquine as a candidate ALKBH5 inhibitor. Transcriptomic changes following mefloquine treatment were assessed by RNA sequencing. In vitro studies were conducted using human and murine OS cell models. Direct interaction between mefloquine and ALKBH5 was validated using surface plasmon resonance and m6A dot blot assays. Therapeutic efficacy was evaluated in orthotopic intratibial and experimental metastasis mouse models, including assessment of tumor growth, metastatic burden, and response to immunotherapy. Results: Genetic loss of ALKBH5 significantly reduced OS cell proliferation, primary tumor growth, and metastatic burden in vitro and in vivo. Mefloquine treatment phenocopied ALKBH5 depletion, suppressing tumor growth and metastasis across multiple OS models. RNA sequencing revealed upregulation of immune-related pathways following mefloquine treatment. In vivo, mefloquine significantly reduced primary tumor volume and metastatic disease and enhanced response to immunotherapy. Conclusions: These findings identify ALKBH5 as a clinically relevant regulator of osteosarcoma progression and antitumor immunity. Mefloquine, an FDA-approved antimalarial drug, demonstrates potent antitumor and immunomodulatory activity through ALKBH5 inhibition and represents a promising repurposing strategy for osteosarcoma treatment. This work provides a strong preclinical rationale for further clinical investigation of ALKBH5-targeted therapies, including combination strategies with immunotherapy, in patients with osteosarcoma.

Analyzing dual threat shifts in gastric carcinoma and sepsis mortality in the United States from 1999-2020: Insights from CDC database.

e16067 Background: Gastric carcinoma remains a significant cause of cancer mortality in the United States. Although overall mortality rates have declined, persistent disparities exist across racial, age, and geographic groups. For cancer patients, sepsis—a life-threatening infection response—is a major fatal complication. Analyzing linked mortality data is crucial for identifying high-risk populations, understanding the burden of cancer-associated infections, and guiding targeted prevention and treatment strategies to improve outcomes and achieve health. Methods: This cross-sectional study used CDC WONDER mortality data from 1999–2020 for adults aged 25 years and older. Causes of death were identified using ICD-10 codes, and age-adjusted mortality rates (AAMRs) were calculated across sex, race/ethnicity, age, census regions, and urban–rural categories. Mortality trends were assessed using Joinpoint regression to estimate average annual percentage changes (AAPC) with 95% confidence intervals (CIs) and statistical significance. Results: From 1999 to 2020, U.S. stomach cancer mortality declined overall, with AAMRs decreasing from 0.29 to 0.22 per 100,000 (AAPC = –0.8%, 95% CI: –1.64 to 0.04). Significant declines occurred among adults aged 65–74 (APC = –1.7%, 95% CI: –2.32 to –1.05), 75–84 (APC = –1.9%, 95% CI: –2.65 to –1.05), and ≥85 years (APC = –3.0%, 95% CI: –4.02 to –1.99). Adults 45–54 years experienced increasing mortality after 2005 (APC = 5.1%, 95% CI: 2.82 to 7.46), while rates among 55–64 years remained stable. Male mortality declined significantly (AAPC = –1.24%, 95% CI: –1.93 to –0.54), whereas female mortality showed no significant long term change (AAPC = –0.93%, 95% CI: –2.44 to 0.60). Black (AAPC = –2.25%, 95% CI: –3.02 to –1.47) and Hispanic/Latino populations (AAPC = –1.50%, 95% CI: –2.26 to –0.74) experienced significant declines. Regionally, the Northeast showed the largest decline (AAPC = –2.30%, 95% CI: –3.52 to –1.07), while the Midwest, South, and West demonstrated no significant long term trends. Metropolitan areas declined from 1999–2011 (APC = –2.80%, 95% CI: –4.44 to –1.14). Conclusions: While overall U.S. gastric cancer mortality declined from 1999–2020, this progress is uneven. Significant increases among adults aged 45–54 and stable rates for those 55–64 highlight an emerging concern. Furthermore, declining trends are concentrated in specific demographic groups and regions, such as the Northeast, revealing persistent disparities. These findings underscore the need for targeted prevention and research focused on younger adults and lagging geographic areas.

Phase 1/2 trial of ATR inhibitor berzosertib plus immune checkpoint inhibitor avelumab in patients with advanced cancers with DNA damage response (DDR) gene alterations: Tumor microenvironment–mediated pathways of resistance from correlative data.

3141 Background: Herein we present novel correlative data from baseline and on-treatment tumor and blood sampling with associated therapeutic outcomes from a phase 1/2 trial of ATRi (berzosertib) plus ICI (avelumab) in patients (pts) with advanced cancers with pathogenic mutations in select DDR genes. Methods: 17 pts enrolled on trial, and they received berzosertib (day 1, 8, 15, 22) plus avelumab (day 1 and 15, q28 days). Paired tumor biopsies were collected at baseline and on Day 12 of treatment, with spatial gene expression profiling (Visium) performed on the tumor tissues. Spot-level bioinformatics and manual annotations were performed to identify regions enriched for tumor cells and key TME components. Blood was collected at baseline and longitudinally for high-dimensional CyTOF profiling for immune cell populations and Luminex for circulating cytokines. Results: The ATRi + ICI combination was safe and well tolerated as previously reported, with ORR of 12.5% in this heavily pre-treated study population, with 2 durable RECISTv1.1 partial responses observed in advanced HPV+ vaginal cancer pt with pathogenic somatic RAD51 mutation lasting 23 months and an advanced colorectal cancer with MSH2 mutation lasting >24 months. In liquid sampling (N=16 pts), CyTOF analysis revealed a common baseline monocyte “stress-brake” state marked by elevated MRE11 and impaired antigen presentation. Treatment resulted in relief of innate DNA stress and induction of a myeloid-to-lymphoid immune shift, with subsequent expansion of adaptive T-cell effectors (EM1 CD4 T cells), with the durable responses characterized by an early proliferative CD8 T-cell burst (D12–D28) followed by sustained lymphoid dominance. Luminex assay revealed substantial cytokine remodeling at D12–D28 relative to baseline, with multiple analytes exceeding the predefined effect-size threshold (|log2FC| ≥ 0.58; ~1.5-fold), suggesting an acute inflammatory response and myeloid infiltration. Spatial profiling in non-responders showed high baseline levels of cancer associated fibroblasts (CAFs) and intra-tumoral CNV heterogeneity, with treatment resulting in upregulation of immunosuppressive, pro-survival pathways (SPP1, MIF, MYC, and Annexin). In contrast, the available on-treatment pt tissue from the vaginal cancer responding tumor displayed higher lymphoid infiltrate and lower immune suppression genes. Conclusions: Despite universal acute immune activation in circulation following ATRi + ICI, resistant tumors displayed high CNV heterogeneity, CAFs, and increased immunosuppressive pathways, in contrast to responder tissue. Co-clinical studies will further elucidate targetable mechanisms of resistance and guide further DDRi and ICI combinations. Clinical trial information: NCT04266912 .

A phase 1 study of SHR-3821, an ADCC-enhanced CLDN18.2/4-1BB bispecific antibody, in patients with advanced solid tumors.

4037 Background: CLDN18.2 is a highly selective tumor-associated antigen overexpressed in gastrointestinal malignancies, and has emerged as a promising therapeutic target. 4-1BB is a co-stimulatory receptor expressed on activated immune cells; its activation enhances antitumor immunity. SHR-3821 is an ADCC-enhanced bispecific antibody that specifically targets CLDN18.2 and activates 4-1BB in a CLDN18.2-dependent manner, enabling tumor-specific killing while minimizing systemic toxicity. This phase 1 study aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of SHR-3821 in patients with CLDN18.2-positive advanced solid tumors. Methods: Eligible patients had CLDN18.2-positive advanced solid tumors that had progressed on or lacked standard therapies. Patients received SHR-3821 via intravenous infusion every 3 weeks at prespecified dose levels: 0.1, 1, 3, 10, 15, 20 and 30 mg/kg during dose escalation (using a Bayesian optimal interval design), followed by dose expansion and efficacy expansion at 15 and 20 mg/kg. Primary endpoints included safety, maximum tolerated dose, and recommended phase 2 dose. Results: As of November 30, 2025, 40 patients with CLDN18.2-positive advanced solid tumors (23 gastric cancer [GC], 17 pancreatic cancer [PC]) were treated with SHR-3821 at doses ranging from 0.1 to 20 mg/kg. No dose-limiting toxicities occurred, and the maximum tolerated dose was not reached across the evaluated dose range. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 15 patients (37.5%), most commonly decreased neutrophil count (20.0%), decreased lymphocyte count (7.5%), and vomiting (5.0%). No TRAEs led to death; one (2.5%) patients discontinued treatment due to TRAEs. Preliminary pharmacokinetic analyses demonstrated dose-proportional increases in systemic exposure following a single 1–20 mg/kg administration, with terminal elimination half-lives ranging from 4.2 to 7.0 days. ORR in GC were 22.2% at 15 mg/kg and 37.5% at 20 mg/kg (Table). Conclusions: SHR-3821 showed tolerable safety and promising antitumor activity in patients with CLDN18.2-positive GC and PC. These data support further clinical development of SHR-3821. Clinical trial information: NCT06618651 . Efficacy in GC and PC. GC PC 15 mg/kg(N=9) 20 mg/kg(N=8) 15 mg/kg(N=4) 20 mg/kg(N=7) Confirmed ORR, % (n/N; 95% CI) 11.1(1/9; 0.28-48.25) 0(0/8; 0.00-36.94) 0(0/4; 0.00-60.24) 0(0/7; 0.00-40.96) Confirmed DCR, %(n/N; 95% CI) 55.6(5/9; 21.20-86.30) 62.5(5/8; 24.49-91.48) 50.0(2/4; 6.76-93.24) 42.9(3/7; 9.90-81.59) Unconfirmed ORR * , % (n/N; 95% CI) 22.2(2/9; 2.80-60.01) 37.5(3/8; 8.52-75.51) 0(0/4; 0.00-60.24) 0(0/7; 0.00-40.96) Unconfirmed DCR, %(n/N; 95% CI) 55.6(5/9; 21.20-86.30) 62.5(5/8; 24.49-91.48) 50.0(2/4; 6.76-93.24) 42.9(3/7; 9.90-81.59) ORR, objective response rate; DCR, disease control rate. *Four patients were pending efficacy confirmation.

Radiology-NLP–derived real-world progression endpointing and clinicogenomic correlates after 177Lu-DOTATATE PRRT in pancreatic neuroendocrine tumors in MSK-CHORD 2024.

e16329 Background: Predictive biomarkers for peptide receptor radionuclide therapy (PRRT) in pancreatic neuroendocrine tumors (PanNET) are limited, and existing clinicogenomic series are small. MSK-CHORD links tumor sequencing with NLP-derived radiology features and radiology-anchored progression timelines, enabling scalable real-world endpointing. Methods: PanNET were identified by OncoTree (PANET) in MSK-CHORD 2024 (cBioPortal). PRRT exposure was defined by treatment timeline agent “Lutetium Lu-177 dotatate”; index was first PRRT start. Somatic non-silent alterations (MSK-IMPACT) in MEN1, DAXX, and ATRX were evaluated. Radiology-NLP metastatic site indicators were used as baseline phenotypes. Primary endpoint was time to first post-index radiology-annotated progression (PROGRESSION = Y); censoring occurred at the last post-index progression assessment. Kaplan–Meier estimated time to progression (TTP); exploratory Cox proportional hazards models evaluated covariates. Results: Among 259 PanNET, 55 received 177Lu-DOTATATE. Median age was 65 years (IQR 56–72); 55% were male. Baseline NLP-derived metastatic sites included bone 44% and lung 38% (liver 100%). Median prior systemic agents before PRRT was 2 (IQR 1–3). DAXX/ATRX alterations were present in 47% and MEN1 in 53%. Forty-nine (89%) had ≥1 post-PRRT progression assessment; 39 progressed. Median TTP was 14.9 months and 12-month progression-free probability was 59%. DAXX/ATRX-altered tumors showed longer TTP than wild-type (16.6 vs 11.9 months; HR 0.80, 95% CI 0.42–1.52; p = 0.49). Each additional prior systemic agent was associated with shorter TTP (HR 1.16 per agent; 95% CI 1.02–1.32; p = 0.026). Conclusions: A CHORD-based, radiology-derived progression endpoint enables reproducible real-world assessment of PRRT outcomes in PanNET and supports hypothesis generation for clinicogenomic and radiology-phenotype factors associated with post-PRRT progression. PRRT-treated PanNET (n=55), stratified by DAXX/ATRX alteration. Overall DAXX/ATRX altered DAXX/ATRX wild-type n 55 26 29 Age, median (IQR), y 65 (56–72) 68.5 (63–74) 61 (50–68) Male, n (%) 30 (55) 15 (58) 15 (52) Bone mets (NLP), n (%) 24 (44) 12 (46) 12 (41) Lung mets (NLP), n (%) 21 (38) 8 (31) 13 (45) Prior agents, median (IQR) 2 (1–3) 2 (1–3) 2 (2–3) MEN1 altered, n (%) 29 (53) 19 (73) 10 (34) Evaluable for TTP, n 49 23 26 Median TTP, months (KM) 14.9 16.6 11.9 12-mo progression-free, % 59 72 48

Endometrial cancer mortality and persistent disparities in the United States, 1999–2023.

e17646 Background: Endometrial cancer (EC) is the most common gynecologic malignancy in high-income countries, with a rising mortality burden in the United States. However, long-term EC-specific mortality trends stratified by age, race/ethnicity, geography, and urbanization remain insufficiently characterized. Methods: We analyzed EC-related deaths among adults aged ≥45 years from 1999–2023 using the CDC WONDER database. Deaths were identified using ICD-10 code C54.1. Age-adjusted mortality rates (AAMRs) and crude mortality rates (CMRs) per 100,000 were calculated and stratified by age group, race/ethnicity, census region, state, and urbanization. Temporal trends were evaluated using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals (CIs). Results: A total of 125,502 EC-related deaths occurred from 1999–2023. Overall AAMR increased from 6.40 in 1999 to 10.42 in 2023, with an overall AAPC of 2.17% (95% CI, 1.35–2.98). Mortality declined from 1999–2014 (APC −0.54%; 95% CI, −0.86 to −0.21), followed by a sharp increase from 2014–2017 (APC 13.22%; 95% CI, 6.16–20.74) and continued rise from 2017–2023 (APC 3.78%; 95% CI, 2.83–4.73). Age-specific mortality increased markedly with advancing age. CMRs were lowest among individuals aged 45–54 years (1.37 during 1999–2020; 2.12 during 2021–2023) and highest among those aged ≥85 years (18.47 to 25.87), with an APC of 7.02% (95% CI, 5.52–8.54) after 2014. Racial disparities were pronounced. From 1999–2017, Black individuals had the highest AAMR (10.05; AAPC 1.56%; 95% CI, −0.06 to 3.20). From 2018–2023, the highest AAMR was observed among Native Hawaiian or Other Pacific Islanders (23.38). Both rural and urban areas demonstrated rising mortality after 2013, with APCs of 6.44% (95% CI, 4.29–8.64) and 8.46% (95% CI, 7.21–9.71), respectively. Regionally, AAMR was highest in the Northeast (AAPC 1.92%; 95% CI, 0.69–3.17), while the Midwest showed the greatest recent increase (AAPC 2.04%; 95% CI, 1.33–2.75). The District of Columbia had persistently highest state-level AAMRs. Conclusions: Endometrial cancer mortality has increased substantially in the United States over the past two decades, with widening disparities by age, race/ethnicity, region, and urbanization. Older adults, Black and Pacific Islander populations, and residents of high-burden regions experience the greatest mortality risk. These findings highlight an urgent need for equity-focused prevention, earlier diagnosis, and improved access to high-quality care.

Testosterone suppression, safety, and adherence with relugolix in patients with metastatic prostate cancer: 6-month subgroup analysis of the OPTYX study.

e17057 Background: Relugolix is an oral androgen deprivation therapy used for the treatment of advanced prostate cancer (PC). OPTYX (NCT05467176) is an ongoing multicenter, prospective, observational study of relugolix treatment in the United States. There is limited published literature regarding patients with metastatic PC (mPC) initiating relugolix monotherapy or combination systemic therapy. We report testosterone suppression, serious adverse events (SAEs), and adherence data from baseline through 6 months in a subgroup of patients with mPC initiating relugolix monotherapy or relugolix in combination with other systemic prostate therapies. Methods: Patients with PC were enrolled in OPTYX if they initiated relugolix ≤1 month prior to study enrollment and intended to remain on relugolix for ≥4 months. Six-month testosterone suppression, SAEs, and adherence were assessed in patients with mPC. Monotherapy or combination therapy categorization was based on baseline use. Adherence is assessed by the Simplified Medication Adherence Questionnaire. All patients have ≥6 months of data after enrollment. The study is ongoing and data will be collected for a minimum of 2 years with no mandatory study visits required. Results: A total of 255/999 patients enrolled in OPTYX had mPC. Median age at baseline was 71 years; 14.5% were Black and 0.4% were Asian. At relugolix initiation, 64.7% received monotherapy and 35.3% received combination therapy. Of patients with available testosterone data at 1 month (earliest timepoint assessed), 95% (n = 38/40) and 81% (n = 17/21) of patients who initiated monotherapy and combination therapy, respectively, achieved castrate levels ( < 50 ng/dL). All patients assessed at 3 months (monotherapy, n = 47/47; combination therapy, n = 28/28) and 92% (n = 55/60) and 97% (n = 33/34) of patients (monotherapy and combination therapy, respectively) assessed at 6 months achieved castrate testosterone levels. Overall, 7.8% (20/255) of patients (monotherapy, 9.1%; combination therapy, 5.6%) initiating relugolix experienced ≥1 SAE; most common SAEs were anemia (n = 2) and atrial fibrillation (n = 2). One patient in each group (monotherapy, 0.6%; combination therapy, 1.1%) experienced cardiovascular (CV)-related SAEs. Patient adherence was high at 6 months, with 96% of patients (monotherapy, 96%; combination, 95%) reporting taking relugolix at the appropriate time each day and 81% (monotherapy, 80%; combination, 83%) reporting never forgetting to take relugolix even once. Conclusions: Using clinical practice data, relugolix treatment led to successful testosterone suppression, low rates of documented SAEs and CV-related SAEs, and high adherence at 6 months in patients with mPC. These results were similar in patients initiating monotherapy and combination therapy. Clinical trial information: NCT05467176 .

Lenalidomide Plus Rituximab for Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: 5-Year Follow-Up and Subgroup Analyses From the Phase III AUGMENT Trial

The phase III AUGMENT trial (ClinicalTrials.gov identifier: NCT01938001 ) demonstrated improved efficacy for lenalidomide plus rituximab (R 2 ) versus rituximab with placebo (R-placebo) in patients with relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). Here, we present the long-term follow-up results and prespecified subgroup analyses of patients with follicular lymphoma (FL), including those 70 years and older. Patients with R/R grade 1 to 3a iNHL were randomly assigned 1:1 to receive R 2 or R-placebo. In this long-term follow-up report, progression-free survival (PFS) was assessed per the investigator. Secondary end points included overall survival (OS) and safety. Of the 358 randomly assigned patients (intent-to-treat [ITT] population), 295 had FL (≥70 years, n = 66). At long-term follow-up (median, 65.9 months), in the ITT iNHL population, PFS (hazard ratio [HR], 0.50 [95% CI, 0.38 to 0.66]) and OS (HR, 0.59 [95% CI, 0.37 to 0.95]) were improved with R 2 versus R-placebo. Safety findings were consistent with the primary analysis. Improved long-term efficacy with R 2 versus R-placebo and manageable safety with R 2 were observed in patients with FL, including those 70 years and older. With a follow-up of >5 years, data from the AUGMENT trial continue to support the use of R 2 as a standard of care for patients with R/R iNHL.

Prognostic stratification using baseline objective clinical information in patients with stage IV lung cancer receiving best supportive care alone as initial treatment: A multicenter retrospective study (WJOG20824L).

12054 Background: Despite expanded systemic therapy for lung cancer, best supportive care (BSC) alone remains the initial treatment for some patients, often due to advanced age, poor performance status (PS), or comorbidities. However, large-scale data on prognostic heterogeneity and risk stratification in this population are limited. We aimed to stratify overall survival (OS) in stage IV lung cancer patients initially managed with BSC alone using baseline clinical information. Methods: We analyzed a multicenter database from WJOG15121L including 6,751 patients with stage IV lung cancer diagnosed between January 2016 and December 2019, identifying those who received BSC alone as initial treatment. Sixty-two baseline variables (demographics, comorbidities, genomic alterations, and laboratory data) were assessed. The primary analysis was conducted in complete cases (BSC complete cohort), with multiple imputation (MI) in the entire cohort as sensitivity analysis. A boosting-based model was used to derive a prognostic risk score for OS and to stratify patients into low-, medium-, and high-risk groups based on the risk score distribution. Survival outcomes were summarized using Kaplan–Meier methods with log-rank tests. Cox regression with Lasso regularization (Cox-Lasso) was also performed as an alternative approach to assess robustness. Results: A total of 923 patients received BSC alone as initial treatment; 266 comprised the BSC complete cohort. The BSC population was elderly (mean age: 75.8 years) with a high proportion of poor PS (ECOG PS ≥2: 74.8%). Kaplan–Meier–based risk stratification separated OS (median OS: 277 vs 74 vs 25 days for low-, medium-, and high-risk groups, respectively). The Kaplan–Meier–estimated 90-day OS rates were clearly separated across the three groups (75.4% vs 29.8% vs 0%; log-rank p < 0.001). Baseline characteristics differed by risk group, including PS and metastatic burden (e.g., liver metastasis). Risk stratification was largely driven by routinely available laboratory markers (e.g., LDH, neutrophil count, CRP, ALP, platelet count). Findings were consistent in the MI-based sensitivity analysis and were broadly supported by the Cox-Lasso approach. Conclusions: Among patients with stage IV lung cancer initially managed with BSC alone, outcomes are heterogeneous and can be stratified into clinically meaningful risk groups using baseline clinical information. Kaplan–Meier summaries (median OS and 90-day OS) demonstrate marked differences across risk strata, and the dominant contribution of routine laboratory variables highlights the potential practicality of this approach in real-world settings. Further validation and comparative analyses with patients receiving systemic therapy who share similar risk profiles are ongoing.

CLD-401: A next-generation systemic gene therapy for tumor-localized expression of IL-15 superagonist.

e14517 Background: RedTail is a next-generation gene therapy platform engineered for systemic delivery and highly selective, tumor-specific payload expression. The platform uses a tumor specific, extracellular enveloped vaccinia virus (EEV) expressing a chimeric form of CD55, providing resistance to complement and neutralizing antibodies, and enabling systemic administration, that has been engineered to only replicate in tumor cells. Our lead candidate, CLD-401, delivers an IL-15 superagonist (IL-15[N72D]-IL-15Rα), a potent cytokine that induces NK and CD8⁺ T cell responses in the tumor microenvironment (TME), driving robust antitumor immunity and efficacy. This platform represents a promising approach for safe, effective immuno-gene therapy in metastatic cancer. Methods: CLD-401 was administered systemically in syngeneic tumor-bearing mice. ELISA quantified IL-15 superagonist in serum and tumor lysates. Flow cytometry assessed immune infiltration and qPCR evaluated viral amplification in tumors versus normal tissues. Results: CLD-401 demonstrated robust production of EEV overexpressing CD55 and IL-15 superagonist, enabling selective tumor targeting without immune clearance after systemic delivery. CD55 overexpression conferred resistance to complement-mediated lysis and neutralizing antibodies. Following intravenous administration, CLD-401 efficiently homed to tumors and remodeled the TME, inducing substantial immune cell infiltration. Within tumors, CLD-401 amplified and reprogrammed tumor cells to produce high levels of IL-15 superagonist locally, while systemic exposure to IL-15 remained minimal, confirming tumor-localized payload delivery. This localized cytokine drove profound TME remodeling and resulted in complete tumor regression in murine breast and lung cancer models. Pharmacokinetic analysis of viral clearance and IL15 expression informed an optimized multidose regimen that maximized therapeutic response. In vitro, secreted IL-15 superagonist demonstrated functional activity by activating human and murine immune cells. qPCR confirmed tumor-specific viral amplification with negligible replication in normal mice or human tissues/cells, underscoring the platform’s tumor selectivity and safety. Conclusions: CLD-401 combines tumor-selective amplification with localized cytokine delivery, achieving potent antitumor immunity and durable responses while minimizing systemic toxicity. These findings support CLD-401 as a promising candidate for clinical development in targeting metastatic cancer.

Facility staff perspectives on the implementation of Maternal and Perinatal Death Surveillance and Response in six health facilities in Kigoma, Tanzania

Background Maternal and Perinatal Death Surveillance and Response (MPDSR) is an important accountability mechanism for preventing avoidable deaths and addressing gaps in care. Health facilities in resource constrained settings often face barriers to implementing and sustaining MPDSR. The purpose of this study was to identify factors that may influence MPDSR implementation outcomes in health facilities in Tanzania. Methods Semi-structured, in-depth interviews (IDIs) were conducted in January 2024 with 17 delivery care providers (e.g., doctors, midwives, anesthesiologists) and 5 health administrators who oversaw or facilitated the facility’s MPDSR process. The implementation outcomes framework and the Practical, Robust, Implementation and Sustainability Model (PRISM) were used to guide the study, the development of interview guides, and analysis. We analyzed transcripts using a multistage approach and the constant comparative method. Results We identified several factors that may have impacted MPDSR implementation outcomes, which we grouped into three primary themes: (1) organizational and staff perspectives on MPDSR, (2) characteristics of the implementation setting, and (3) implementation and sustainability infrastructure. Subthemes included more specific barriers and facilitators that were related to MPDSR implementation outcomes. Prominent facilitators included positive perspectives of MPDSR, ongoing training and mentorship, and community engagement. Major barriers included lack of organizational readiness, resource, financial and other constraints, and blame culture. Conclusions Identifying factors that influence MPDSR implementation outcomes is important for understanding barriers and facilitators to implementation. Fostering safe environments (i.e., no blaming), addressing barriers to staff participation and motivation, and implementing monitoring systems for MPDSR recommendations may help strengthen implementation outcomes and, ultimately, sustainability.

Ultrasonic investigation of PEG–Ethanol–Epoxy–TiO₂ nanocomposite: Insights into coating suitability via thermoacoustic parameters

Harmonizing High Phosphorescence Efficiency and Stretchability in Flexible Afterglow Materials Through Microphase Engineering

ABSTRACT Organic ultralong room‐temperature phosphorescence (OURTP) materials are promising for flexible optoelectronics but often suffer from a trade‐off between phosphorescence efficiency and mechanical flexibility. To overcome this limitation, a block copolymer system is developed through the incorporation of coronene into poly(styrene‐isoprene‐styrene) (SIS). Within this structure, the rigid polystyrene (PS) segments immobilize the phosphors and facilitate charge‐transfer‐mediated OURTP, resulting in high phosphorescence efficiency (Φ = 54.9%, τ = 6.26 s). Concurrently, the polyisoprene (PI) segment ensures outstanding elasticity, endowing the material with ultra‐stretchability (2380.5% strain) and fatigue resistance (withstanding 600% strain over 40 cycles). The system also maintains intrinsic morphological homogeneity, effectively avoiding phase separation. Through microphase engineering, this work successfully reconciles the long‐standing conflict between luminescence and flexibility, providing a general design strategy for multifunctional polymers suitable for wearable electronics that demand both deformability and phosphorescent capability.