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Clinical and translational results from the phase 1 portion of the phase 1/2 study to evaluate CHM-2101, an autologous cadherin 17 (CDH17) chimeric antigen receptor (CAR) T cell therapy for the treatment of relapsed or refractory gastrointestinal cancers.

2536 Background: CHM-2101 is a Cadherin 17 directed autologous CAR T-cell product being developed to address the continuing unmet medical need for effective therapy against relapsed or refractory gastrointestinal (GI) cancers. Solid tumors of the GI tract such as gastric cancer, colorectal cancer (CRC) and neuroendocrine tumors (NETs) are devastating diseases associated with poor outcomes and more than 1.3 million global deaths annually. Despite advances in surgical and medical treatment of these solid tumors, the prognosis for patients with relapsed or refractory disease remains poor. There remains a need for innovative and effective treatments for patients with advanced and treatment-recalcitrant GI malignancies. Methods: The ongoing clinical trial is a seamless Phase 1/2 study enrolling subjects with gastric cancer, CRC or NETs of the midgut or hindgut. Enrolled subjects undergo screening and apheresis to enable manufacturing of CHM-2101. After completing apheresis, bridging therapy is permitted to provide disease control. After confirming successful CHM-2101 manufacturing and washout of bridging therapy, study subjects receive 3 days of lymphodepleting chemotherapy (fludarabine 30mg/m2/day and cyclophosphamide 500mg/m2/day). After two days of rest, subjects receive a one-time IV infusion of CHM-2101. Results: As of October 24, 2025, 13 subjects have been enrolled with 2 screen failures. Eleven of eleven successful manufacturing runs enabled treatment of 9 subjects to date (4 subjects at Dose Level 1 and 5 subjects at Dose Level 2). Most AEs were Grade 1-2. Aside from lymphodepleting chemotherapy-related cytopenias, Grade 3 Treatment-Related Adverse Events (TRAEs) were Cytokine Release Syndrome (CRS) and Enterocolitis in 1 subject each. There have been no Grade 4 or 5 TRAEs or DLTs. After IV infusion, CHM-2101 was noted to expand and persist (by flow and ddPCR) in the peripheral blood of all treated subjects. Conclusions: CHM-2101 has demonstrated cellular expansion and persistence with clinical tolerability in study subjects with advanced GI cancers at two dose levels. Enrollment of patients at Dose Level 3 is ongoing at US Cancer Centers. Clinical trial information: NCT06055439 .

Thymoma, type A, NOS: A National Cancer Database study of demographic and socioeconomic factors.

e20170 Background: Type A Thymoma (TAT), not otherwise specified (NOS), is a rare, indolent thymic epithelial tumor composed of spindle-shaped cells with few or no immature lymphocytes. This subtype of thymoma generally carries a favorable prognosis with excellent long-term survival rates, given the low risk of metastasis or recurrence following complete surgical resection of the encapsulated tumor. This study aims to use the National Cancer Database (NCDB) to analyze the demographic and socioeconomic factors in patients with a confirmed diagnosis of TAT NOS since current data relies on smaller institutional case series and cohorts as well as the broader limitation of epidemiological data. Methods: A retrospective cohort analysis using the 2004–2020 NCDB included 926 patients with a histologically-confirmed diagnosis of TAT, NOS ICD-O-3 code (8581). Demographic factors (age, sex, race, Hispanic status, educational attainment, insurance status, facility type, distance from facility, and Charlson-Deyo score) were analyzed using descriptive statistics, and incidence trends were interpreted through regression analysis. Results: The incidence rate of new diagnoses remained relatively stable over 2004-2020 (R^2 =0.59). Men (51.9%) were most likely to be diagnosed and average age at diagnosis was 67.1 years (SD = 12.2, range 15 – 90 years). The common primary site was the thymus (99.6%). The majority of this cohort were White (77.8%), Non-Hispanic (89.3%), and lived in metropolitan areas (86.7%). Patients were treated in an academic/ research program (39.6%) or a comprehensive community cancer program (36.3%), located in the Middle Atlantic (22.1%) or the South Atlantic (21.1%). In most cases, patients were insured by Medicare (56.5%) or privately insured (32.6%) and had no comorbidities (71.4%, Charlson-Deyo = 0). The common treatment was a surgical procedure of the primary site (84.8%) with most cases undergoing a complete thymectomy (40.5%), followed by radiology (32.6%) or chemotherapy (11.2%) as the primary treatment. A minority of patients received palliative care (1.5%). Long-term survival at two, five, and ten years was 98%, 95%, and 90% respectively. Conclusions: To our knowledge, no prior NCDB analysis has investigated TAT NOS, and this work fills an important knowledge gap in this area. Consistent with previous research, TAT NOS most commonly affected Non-Hispanic (89.3%), White patients, with tumors predominantly being found in the thymus. Socioeconomic characteristics of the cohort included the majority living in metropolitan areas and treated at an academic/research center. Additional studies are needed to understand the associations between demographic and socioeconomic factors of TAT NOS diagnosis, treatment approaches, and survival outcomes.

Integrating supervised physical activity into breast cancer survivorship care.

e24050 Background: Although the benefits of physical activity are well established, participation rates among cancer survivors remain low. Barriers include the lack of structured survivorship care plans, limited access to exercise programs, geographic constraints, and financial limitations. To address these challenges, a community-based integrative oncology program has been implemented within the Italian National Health System for two years, combining tailored lifestyle counseling with adapted physical activity (APA) to promote healthy behaviors among cancer survivors. Methods: A prospective, observational study evaluated the feasibility. During scheduled oncology follow-up, cancer survivors with lifestyle-related risk factors were clinically referred to the program. Ninety-seven participants, mainly breast cancer women, received a one-hour individualized lifestyle medicine consultation followed by supervised group-based adapted physical activity (APA) sessions twice weekly for 8–12 weeks. Each 60-minute session included mobility, resistance training, core stability, and balance exercises, supervised by a kinesiologist and orthopedic specialist. Functional outcomes were assessed pre- and post-intervention using the six-minute walk distance (6MWD), five-times sit-to-stand test (5xSTS), handgrip strength (HGT), and single-leg stance (SLS). Adherence, safety, and patient satisfaction were recorded. Physical activity participation was reassessed at six-month follow-up. Results: At baseline, participants’ fitness levels were significantly lower than those of an age-matched healthy reference group (48-65 years). Adherence, defined as the proportion of training sessions attended out of those prescribed, was 72.5 ± 18.5%, with a total drop-out rate of 19%. After the program, the 6MWD increased by approximately 80 m, and SLS errors decreased by 1.4 compared to baseline ( p < 0.001 ). HGT improved by 1.40 kg, and 5xSTS time decreased by 1.7 seconds ( p < 0.05 ). No adverse events were reported, and 88% of participants rated the program as excellent. At baseline, only 30% of participants were physically active. At six-month follow-up, 65% continued to engage in regular physical activity with a kinesiologist or in walking groups. Among the remaining participants, 31% discontinued due to health-related issues unrelated to cancer, and 4% stopped due to lack of time. Conclusions: Our community-based oncology program educates participants on integrating physical activity into survivorship care. Accessibility, professional supervision, group support, and clinical endorsement are key drivers of engagement. These findings highlight both the challenges and opportunities in implementing effective survivorship exercise programs and may inform future initiatives.

Quantitative pre-cystectomy ctDNA levels for identification of ctDNA-positive patients with surgically curable loco-regional disease versus those with occult micrometastatic progression.

4577 Background: Radical cystectomy (RC) is a life-altering operation associated with substantial morbidity. Despite its curative intent for muscle-invasive urothelial carcinoma (MIUC), approximately 50% of patients experience metastatic recurrence after surgery. Identifying patients destined to relapse despite RC could help spare them from the morbidity of surgery and instead direct them toward alternative systemic therapies. While ctDNA-positive assays post-neoadjuvant therapy (NAT) but pre-cystectomy are associated with a poor prognosis, a subset of patients with ctDNA positive assays pre-cystectomy “clear” ctDNA with cystectomy alone (Powles, ASCO, 2025). We hypothesized that quantitative pre-cystectomy ctDNA thresholds may therefore distinguish local, surgically curable, bladder cancer versus micrometastatic disease. Methods: We conducted a retrospective single-institution cohort study of patients undergoing RC who had tumor-informed ctDNA (Signatera) assays ≤60 days pre-surgery and within ±30 days of a 3-month postoperative landmark. The primary outcome was ctDNA positivity at this landmark. The analyses proceeded in two steps: (1) association between log-transformed pre-cystectomy ctDNA and 3-month ctDNA positivity, assessed using logistic regression; and (2) derivation of the maximal quantitative preoperative ctDNA threshold >0.02 Mean Tumor Molecules per Milliliter (MTM/ml) using constrained optimization (target sensitivity ≥80%, specificity ≥50%), with internal validation via Efron-Gong bootstrap resampling. Results: Of 45 patients with MIUC meeting inclusion criteria, 10 (22.2%) received NAT. Higher pre-cystectomy ctDNA correlated with ctDNA positivity at the post-cystectomy landmark timepoint (odds ratio per 10-fold increase 1.6, 95% CI 1.2–2.4; p=<0.01). A pre-cystectomy ctDNA threshold ≥0.06 MTM/ml (95% CI 0.04–2.475) demonstrated optimal performance characteristics and was confirmed on bootstrap validation (sensitivity 81.6% [95% CI 61.1–88.9%], specificity 66.4% [95% CI 51.9–96.3%], positive predictive value [PPV] 63.8% [95% CI 55.2–91.7%], and negative predictive value [NPV] 85.1% [95% CI 78.8–88.9%]). Conclusions: Higher pre-cystectomy ctDNA values correlate with a higher likelihood of a persistent ctDNA-positive assay at 3 months post-cystectomy. In this dataset, a ctDNA threshold of ≥0.06 MTM/ml identified patients with high sensitivity and NPV for post-operative micrometastatic disease. Further validation of these findings, and threshold, in larger cohorts (with or without NAT) are needed to refine MIUC care by testing strategies involving (alternative) NAT versus proceeding with cystectomy.

Response in first-in-human chemotherapy-free combination immunotherapy targeting lymphopenia in recurrent glioblastoma multiform (GBM): Nogapendekin alfa inbakicept (NAI) and PD-L1 t-haNK plus bevacizumab (BEV).

e14079 Background: Treatment for recurrent GBM is limited and associated with high mortality. We hypothesize that standard of care for GBM induces severe lymphopenia and, by treating lymphopenia both through in-vivo activation of NK & T cells (via NAI subcutaneous injection) and ex-vivo infusion of NK cells (PD-L1 CAR-NK cells), OS can be prolonged. We hypothesize that lymphocytes, responsible for immunogenic cell death and measured by absolute lymphocyte count (ALC), is key to prolonged survival. NAI, an IL-15 receptor agonist, is the first treatment to address lymphopenia by activating and proliferating NK and T-cells. Methods: Phase 2 QUILT-3.078 trial (NCT06061809) of participants with GBM ( IDH WT) who recurred after surgery and temozolomide/XRT. Fourteen participants received PD-L1 t-haNK, an off-the-shelf NK cell therapy with a chimeric antigen receptor (CAR) for PD-L1, NAI and BEV, every two weeks, as outpatients. Five patients also received concurrent tumor treating fields. ALC levels were measured through data cutoff (January 13, 2026). Results: 14 participants have received 139 total doses, with 7/14 (50%) remaining on therapy. One participant had radiographic complete response after four doses. ALC trend increased from baseline and was maintained through cycle 9 among evaluable participants. Median follow-up is 6.75 months (range 2.4-9.3 months) with four deaths on-study, mOS has not been reached. Ten patients had any SAE, of which one was suspected to be related to BEV (pulmonary embolism) and two SAEs were suspected to be related to the experimental therapy (encephalopathy, temporal arteritis). No CRS or ICANS were observed. Conclusions: These findings support that reconstituting lymphocytes (NK & T cells) results in response, including complete response, in recurrent GBM. This is the first report of disease response in participants with recurrent GBM who received orchestrated systemic immunotherapy with CAR-NK cells combined with an IL-15 agonist and BEV. The potential of reversing lymphopenia induced by SOC treatment, prolonging survival, and improving prognosis across tumor types, may be a paradigm change in cancer care. The QUILT-3.078 Phase 2B expansion study is ongoing and a randomized clinical trial in first and second line GBM patients is in development. At the time of submission, 23/34 participants have enrolled on the QUILT-3.078 Phase 2/2B study and updated data will be presented. Clinical trial information: NCT06061809 .

The role of neutrophil-released myeloperoxidase in cancer-associated cachexia in patients with pancreatic cancer and in a murine cachexia model.

e24096 Background: Cancer-associated muscle wasting (i.e. cachexia) is largely driven by inflammatory mediators and affects most patients with gastrointestinal cancers. Elevated neutrophil counts have been demonstrated in cachectic patients and preclinical models. Neutrophils exert their catabolic effects through the release of peroxidases, namely myeloperoxidase (MPO). Interestingly, MPO inhibitors have shown promising results in mitigating atherosclerosis (NCT03611153); however, their ability to mitigate cachexia has not been investigated. The purpose of this study was to determine the role of MPO in cachexia progression in pancreatic cancer patients and a murine cachexia model. Methods: Serum was collected from 49 patients with locally advanced or metastatic pancreatic cancer at Atrium Health Levine Cancer within the Atrium Health Wake Forest Baptist Comprehensive Cancer Center. Patients were separated into 2 groups based on body weight (BW) loss within 3-months of diagnosis (WS: < 5% BW loss; CX: ≥5% BW loss). Additionally, publicly available SKM CD45+ cell scRNAseq of pancreatic cancer patients was re-analyzed. Proteomic analyses of patient serum are ongoing and will assess cachexia-related cytokines (MPO, TNFα, IL-6, IL-1β, Leptin, GDF-15, IGF-1, P-Selectin, TNFS14, and CCL2). CD2F1 mice were implanted with 10^6 cachexia-inducing C26 or heat-killed tumor cells. Results: Among 49 patients (22 without cachexia, 27 with cachexia), baseline demographic and clinical characteristics were similar between groups (all p > 0.05). Mean age was 64 vs 67 years, and half were female. Most patients were White/Caucasian (74%) and Non-Hispanic/Latinx (98%). Disease stage was similarly advanced in both groups, with 76% with stage IV disease at diagnosis. Preliminary data demonstrated a trend toward higher circulating MPO levels in CX patients (WS: 25.35 ± 11.4 ng/mL; CX: 29.57 ± 11.1 ng/mL, p = 0.10). CD45+ scRNAseq of patients revealed 3 transcriptionally distinct neutrophil subclusters in SKM, characterized as 1) inflammatory/invasive, 2) immunosuppressive, and 3) “aged” N2-like. Similarly, cachectic mice (-10% BW loss, p = 0.017) had significantly higher circulating MPO levels compared to non-tumor mice (167.2 ± 49.3 ng/mL vs. 33.21 ± 1.5 ng/mL; p = 0.01), with increased SKM neutrophils (9.3-fold; p < 0.01) with markedly elevated MPO gene expression ( > 17-fold) and elevated SKM MPO protein expression (3.9-fold; p = 0.01). Conclusions: These findings suggest an association between MPO and cancer cachexia in pancreatic cancer patients and a murine cachexia model. Together, these findings support MPO as a biologically plausible therapeutic target, pending ongoing mechanistic studies.

Association of <i>Streptococcus anginosus</i> with gastric cancer progression via 2-picolinic acid.

e16136 Background: Gastric cancer (GC) is one of the most common cancers and a leading cause of cancer mortality. A diverse community of microorganisms is present in the human stomach and the host-microbe interactions contribute to carcinogenesis and progression of GC. Streptococcus anginosus (SA) was enriched in the gastric mucosa of patients with GC and may promote gastric inflammation, atrophy, and tumorigenesis. However, the potential mechanism is still not fully revealed. Methods: In this work, multi-omics including microbiome, transcriptome, and metabolome data combined with in vivo and in vitro studies were conducted to investigate the potential role and mechanism of SA in process of GC. Results: We analyzed the gastric microbiota of paired tumoral, peritumoral and normal tissues obtained from 144 GC patients by16S rRNA sequencing. SA was enriched stepwise in the normal, peritumoral and tumoral tissues. High level enrichment of SA in tumoral tissue showed poorer prognosis than low level group based on Kaplan-Meier analysis. We isolated and cultured SA from GC tissue, and GC cells co-cultured with SA or treated with SA metabolites enhanced cell proliferation, colony formation, migration and invasion abilities. SA also promoted tumor proliferation in vivo based on mouse transplanted tumor model. Metabolomic analysis showed the elevated level of 2-picolinic acid after treated with SA. We verified the promotional role of 2-picolinic acid on cell proliferation, colony formation and migration in vitro. Conclusions: Thus, this study demonstrated that SA plays significant roles in the progression of GC, and its metabolite, 2-picolinic acid, maybe the key factor in host-microbe interactions.

Financial toxicity and quality of life in advanced lung cancer: The role of depressive symptoms.

e24110 Background: Financial toxicity (FT) is a critical burden in individuals with advanced lung cancer and is strongly associated with impaired health-related quality of life (HRQoL). However, the psychological mechanisms driving this association remain insufficiently understood. Methods: This cross-sectional study enrolled 251 patients with advanced lung cancer in Taiwan. FT was assessed using the FACIT-COST (↑ scores indicate ↓ FT). Depressive symptoms were assessed using PHQ-9. General and lung cancer-specific HRQoL, were assessed using the EORTC QLQ-C30 and QLQ-LC29, respectively. Causal mediation analysis with 1,000 bootstrap resamples was employed to estimate the average causal mediation effect (ACME) and average direct effect (ADE). Results: The mean COST score was 25.8±10.1, with 41.8% of participants experiencing moderate-to-severe FT. Lower COST scores (↑ FT) were significantly associated with ↑ depressive symptom severity (r = −0.47, p &lt; .001) and poorer global HRQoL (r = 0.34, p &lt; .001). Among QoL domains, social functioning was the most severely impaired, alongside lung cancer-specific stressors such as fear of progression and future health concerns. Causal mediation analysis revealed that depressive symptoms significantly mediated the relationship between FT and HRQoL (ACME = 0.33, 95% CI: 0.00–0.69; p = .050). Notably, the direct effect of FT on HRQoL was not statistically significant (ADE = 0.12; p = .62), suggesting that depressive symptoms mediate this association. Conclusions: Depressive symptoms appear to play a central role in linking FT to impaired HRQoL among patients with advanced lung cancer. These findings suggest that mitigating the psychological sequelae of financial burden may be as critical as providing direct financial assistance. Integrating psychosocial screening and targeted mental health support into supportive care strategies may help alleviate the clinical impact of FT and improve patient-centered outcomes.

Patient correlates of patient-provider communication and financial toxicity in Black and White patients with cancer.

e13730 Background: Financial toxicity, the burden of treatment cost, affects up to half of people with cancer and can affect survival. Financial toxicity is a health equity issue, disproportionately affecting Black patients. This cross-sectional study used baseline data from the Discussions of Cost (DISCO) Trial, an RCT to improve patient-provider treatment cost discussions and, in turn, mitigate financial toxicity, to examine whether Black and White patients differed in patient-provider communication perceptions and financial toxicity correlates. Methods: Data were collected from 2021-2025 at an NCI-designated comprehensive cancer center. Participants were Black or White patients diagnosed with solid tumor cancers. At baseline, patients completed demographic measures; communication measures of self-efficacy in patient-provider interactions (e.g., “I am confident I know what questions to ask a provider”); self-efficacy in managing cancer treatment costs (e.g., “I am confident I can understand treatment costs”); and whether they have a provider- or patient-centered approach (e.g., “the provider should decide what gets talked about”); and financial measures including economic burden (e.g., “it’s difficult to live on my income”); treatment cost distress (e.g., “worries about paying for my cancer treatment keep me up at night”); and anticipated material hardship (e.g., “I worry about the financial problems I will have in the future as a result of my treatment”). Comparisons were conducted by patient race. Results: A total of 202 patients participated (116 Black patients, 86 White patients). White patients were more likely to have advanced degrees, a higher annual income, and less likely to have Medicaid compared to Black patients. Black patients reported higher self-efficacy for managing treatment costs ( p = .002) and a higher provider-focused orientation to the patient-provider relationship ( p = .001), than White patients. Black patients reported greater levels of financial burden ( p &lt; .001), cost distress ( p = .005), and anticipated material hardship ( p = .003). There was no difference in self-efficacy for interacting with providers. Conclusions: These results suggest that a communication intervention for patients may help mitigate the experience of financial toxicity, especially for Black patients. Clinical trial information: NCT04766190 . Patient characteristics. Black Patients White Patients p -value Race 116 86 Education &lt; High School High School/GED Some College 2 or 4-year College Degree Graduate/Professional College Trade/Technical/Vocational School 10352626712 0141631187 &lt; .001 Annual Household Income 0 - $19,999 $20,000 - 39,999 $40,000 - 59,999 $60,000 - 79,999 $80,000 - 99,999 $100,000 - 149,999 $150,000 + 53201611431 51215991716 &lt;.001 Insurance Type* Medicaid Medicare Medicare supplement Private None 604911330 113726393 &lt;.001&gt;.99&lt;.001.20.15 *Patients could select more than one

Clinical outcomes of ethnically and racially diverse patients with gynecologic malignancies in phase I clinical trials at a single institution (2021–2024).

e17544 Background: Phase I clinical trials offer a treatment for patients with gynecologic malignancies that have progressed past standard of care treatments, yet there is limited current data on the clinical outcomes of patients enrolled in these trials. This retrospective study evaluates the survival, clinical benefit rate, and toxicity profile of patients with gynecologic malignancies enrolled in Phase I clinical trial drugs at a single institution from February 2021 to November 2024. Methods: A retrospective chart review was conducted on patients with pathologically confirmed gynecologic malignancy who enrolled in Phase I clinical trials at a single institution during the study period. Data collected included demographics, disease characteristics, overall survival (OS), progression-free survival (PFS), clinical benefit rate (CBR), and drug-related toxicities. OS and PFS were measured from the date of Phase I enrollment. CBR was defined as complete response, partial response, or stable disease based on the RECIST criteria. Toxicity was measured using NCI CTCAE, with dose-limiting toxicity defined as Grade 3 or 4. Results: The analysis included 22 patients, consisting of 15 with ovarian histology and 7 with endometrial/uterine histology. The study population was racially and ethnically diverse, with a majority of participants (59%) identifying as members of underrepresented groups, including 36% Black and 23% Hispanic individuals. The median age at the time of enrollment was 67. The median overall survival (OS) was 57 weeks [range: 7.1 - 124 weeks], and the median progression-free survival (PFS) was 8 weeks [range: 3.3 - 101 weeks]. The clinical benefit rate was 40.9%, with 31.8% of all patients achieving stable disease ≥ 4 months. No patients met criteria for partial response or complete response. Grades 3 or 4 hematologic drug-related toxicities occurred in 9.1% of patients. Conclusions: The findings provide contemporary data on outcomes for patients with gynecologic malignancy enrolled in Phase I clinical trials at our institution. The results suggest these drugs could be an avenue for patients who have exhausted existing methods of management for their advanced or recurrent cancers. Further work should continue to monitor the outcomes of patients on Phase I trials for gynecologic malignancies, which will help inform patient counseling and highlight the ongoing necessity for novel and effective agents in this patient population.

Integrated metabolite–network modeling of metabolic nodes and oncogenic signaling in gastrointestinal cancers.

e15506 Background: Gastrointestinal (GI) cancers are driven by metabolic–signaling feedback loops that stabilize tumorigenic phenotypes. However, the mechanistic characterization of how metabolic fluxes interface with oncogenic network rewiring remains incomplete. A computational framework integrating metabolomics with regulatory network inference can address this gap. Methods: Multi-omics datasets were harmonized using a pipeline combining: Differential metabolite calling (XCMS, MetaboAnalyst), Flux–balance inference (iMAT and COBRApy), Network construction (STRING + Cytoscape), Hub prioritization (degree, betweenness, and MCODE modularity), Ligand–target mapping (SwissTargetPrediction and PharmMapper), Molecular docking (Vina), 200 ns Molecular dynamics simulation (GROMACS), and Binding free energy (MM/PBSA). Results: Flux–balance modeling revealed increased glycolytic flux and glutamine anaplerosis supplying the TCA cycle in GI tumors. Mechanistically, excess lactate reinforced HIF1A stability, while elevated α-ketoglutarate supported chromatin remodeling, promoting Wnt/β-catenin activation. Network topology identified PI3K, KRAS, MYC, and MAPK as flux-sensitive hubs with high information centrality. Molecular docking + Molecular dynamics simulation demonstrated that quercetin, luteolin, and epigallocatechin gallate engage catalytic pockets of KRAS-G12D, LDHA, and AKT1 with stable interactions. MM/PBSA revealed strong binding energies, suggesting inhibition of both metabolic and proliferative signaling nodes. Conclusions: Mechanistic flux-network integration shows that natural compounds can collapse GI tumor viability by simultaneously destabilizing metabolic drivers (LDHA, GLS) and oncogenic nodes (KRAS, AKT). This computational framework provides a mechanistic roadmap for multi-target drug discovery. Keywords: gastrointestinal cancers, metabolomics, network pharmacology, molecular docking, molecular dynamics simulation.

Efficacy and safety of tislelizumab combined with chemoradiotherapy in high-risk locoregionally advanced nasopharyngeal carcinoma.

e18071 Background: The poor prognosis of high-risk locoregionally advanced nasopharyngeal carcinoma (LANPC) due to the high incidence of metastasis or local recurrence despite the development of radiotherapy. Immunotherapy has potential efficacy for LANPC, but the optimal treatment model remains unclear. This trial aimed to evaluate the efficacy and safety of tislelizumab combined chemotherapy in patients with high-risk LANPC. Methods: Patients with LANPC (stage III-IVa, AJCC 8th edition, except T3N0-1) were enrolled. All eligible patients received three 21-day cycles of induction treatment (Tislelizumab 200 mg intravenously on D1, gemcitabine 1g/m 2 intravenously on D1 and D8, and cisplatin intravenously 25 mg/m 2 , on D1 to 3) prior to cisplatin concurrent chemoradiotherapy. Adjuvant therapy included eight 21-day cycles (Tislelizumab 200 mg intravenously on D1 and capecitabine 1000mg/m 2 orally twice daily on D1 to 14). The primary endpoint was complete response (CR) rate after induction treatment. Secondary endpoints included objective response rate (ORR) after induction treatment, locoregional failure-free survival (LRRFS), distant metastasis-free survival (DMFS), failure-free survival (FFS), and safety. Results: Between Aug 2024 and Dec 2025, 33 patients were enrolled. As of Jan 2026, 30 patients completed induction treatment and were evaluated. The CR rate after induction treatment was 36.7% (11/30). The overall response rate (ORR) after induction treatment was 93.3% (28/30). The most common treatment-related adverse events were leukopenia, lymphopenia, nausea, transaminitis and anaemia. A few immune-related adverse events such as hypothyroidism, rash and allergic reaction were observed. No grade 5 adverse events occurred. Conclusions: Tislelizumab with standard GP chemotherapy followed by cisplatin concurrent chemoradiotherapy and adjuvant tislelizumab with capecitabine has achieved potential complete response rate and manageable toxicity in patients with LANPC in this trial. Treatment is continued and long-term follow-up is ongoing. Clinical trial information: ChiCTR2400084683.

Echo cancer advisor: A modular AI framework for interpretable, patient-specific oncology decision support.

7522 Background: Oncology increasingly relies on large, heterogeneous datasets spanning genomics, clinical records, imaging, and treatment history. Large language models (LLMs) show promise for synthesizing such information, yet currently suffer from limited transparency, hallucination risk, and poor alignment with real-world clinical reasoning. There is a critical need for AI systems that can integrate multimodal data while preserving interpretability, traceability, and clinician control. Methods: We developed a modular AI decision-support system to assist oncologists in complex clinical reasoning tasks. Unlike monolithic LLM approaches, it decomposes clinical questions into atomic sub-tasks that are executed through structured, auditable pipelines, while integrating curated clinical data (EHR, genomics, pathology), external knowledge bases, and computational analyses via a function-oriented architecture. Each step is independently validated, logged, and audited to ensure correctness. It uses a hybrid local/cloud architecture and was evaluated on real-world oncology use cases in Moffitt Cancer Center’s Multiple Myeloma (MM) cohort, which contains three data modalities: clinical, molecular, and pre-clinical. Clinical data resides in a PHI-compliant Snowflake data warehouse (Moffitt Cancer Analytics Platform, MCAP), including longitudinally-resolved treatment and outcome information from clinical notes, labs, pathology and radiology reports. CD138-enriched bone marrow samples from 1,260 MM patients were molecularly profiled using RNA-seq (n=1,376 biopsies) and whole exome sequencing (WES, n=1,427), whereas 549 tumor samples from MM patients were tested for ex vivo drug sensitivity. Results: This system successfully decomposed complex clinical questions into atomic sub-questions and generated appropriate database queries and software tool calls to retrieve relevant information across heterogeneous data sources. Independently, the system integrated clinical data—including physician notes, pathology reports, laboratory values and pharmacy records—to reconstruct longitudinal patient histories achieving 80% concordance with expert manual abstraction, while reducing case synthesis time from hours to minutes. Importantly, the system preserved transparency by explicitly exposing intermediate reasoning steps and highlighting missing or ambiguous data requiring clinician judgment. Conclusions: We propose a shift from generative AI toward structured, interpretable clinical reasoning systems. By emphasizing modularity, auditability, and human-in-the-loop design, we offer a scalable path toward trustworthy AI deployment in oncology. This framework supports precision medicine not by replacing clinical judgment, but by amplifying it—providing clinicians with transparent, reproducible, and context-aware decision support.

Erythrocyte–anti–PD-1 conjugates in patients with advanced solid tumors resistant to anti–PD-1/PD-L1 therapy: Long-term follow-up of a phase I trial.

2553 Background: Despite the clinical success of immune checkpoint blockade, most patients with advanced solid tumors fail to achieve durable benefit due to limited efficacy and/or immune-related toxicities. αPD-1-Ery is an erythrocyte–antibody conjugate that covalently links an anti–PD-1 antibody to erythrocyte membranes. Unlike conventional antibodies, αPD-1-Ery preferentially accumulates in the spleen, where it remodels the splenic immune microenvironment by expanding effector T cells and reducing immunosuppressive myeloid cell reservoirs, thereby inducing systemic anti-tumor immunity. We previously reported favorable safety and preliminary efficacy of αPD-1-Ery in patients with PD-1/PD-L1–resistant solid tumors. Here, we report long-term follow-up results assessing durability of benefit and exploratory biomarkers. Methods: 14 heavily pretreated patients with 11 types of advanced solid tumors who had progressed on PD-1/PD-L1–containing regimens as their most recent line of therapy were enrolled. Patients received αPD-1-Ery monotherapy at 2×10¹¹ or 3×10¹¹ cells. Endpoints included safety, efficacy, and exploratory correlations between immune biomarkers and clinical outcomes. Results: As of October 31, 2025, all patients had completed treatment, with a median follow-up of 18.9 months. Treatment discontinuation occurred due to disease progression in 57.1% (8/14), CR in 7.1% (1/14), completion of planned treatment cycles in 21.4% (3/14), and other reasons (including AE or withdrawal) in 14.3% (2/14). No DLTs were observed. TRAEs occurred in 64.3% (9/14) of patients, with no grade &gt;3 TRAEs, no grade ≥3 immune-related AEs, and no treatment discontinuations due to TRAEs. αPD-1-Ery demonstrated sustained anti-tumor activity, with a DCR of 78.6% (11/14) and an ORR of 42.9% (6/14; 1 CR, 1 uCR, 4 PR), with improved responses observed in the higher-dose cohort. mPFS was 5.6 months and mOS was 23.4 months. Durable benefit was observed in most responders, with 4/6 maintaining response after treatment discontinuation; 1 received no subsequent therapy and 3 resumed PD-1/PD-L1–based immunotherapy despite prior resistance. mDoR had not been reached (range, 4.8–24.7 months). Exploratory analyses indicated that clinical benefit was observed in both primary (n = 3) and acquired (n = 3) anti–PD-1/PD-L1–resistant patients. Responders had higher baseline circulating PMN-MDSCs and DCs and experienced rapid and sustained PMN-MDSC reduction following treatment. Tumor MMR status was available in 5 patients (all MSS), with objective responses observed in 3. Conclusions: Spleen-directed PD-1 blockade using erythrocyte–antibody conjugates induces durable clinical benefit. αPD-1-Ery represents a novel immunotherapeutic strategy for PD-1/PD-L1–resistant solid tumors and supports further clinical development. Clinical trial information: NCT06026605 .

Sequencing of fallopian tube p53 signature found concurrently with p53 mutant uterine cancers and their somatic mutation profiles.

5610 Background: The tumor protein 53 gene (p53) encodes a protein that suppresses replication of DNA-damaged cells. Mutations resulting in protein dysfunction are common in many cancers. A p53 signature is an aberrant immunohistochemical expression in 12 or more consecutive epithelial cells in the fallopian tube (FT) and is thought to be an early precursor lesion in a spectrum to high grade serous ovarian carcinoma (HGSOC). P53 mutations have also been described in endometrial cancer (EC), specifically high grade histologies such as uterine papillary serous carcinoma (UPSC). NextGen Sequencing of UPSC tumors and concurrent FT lesions has identified overlapping p53 mutations, raising the possibility that these could represent a precursor lesion. The objective of this study was to delineate the clonal relationship between p53-mutation harboring epithelial lesions in the FT and other histologic subtypes of EC, which could have implications for risk stratification, counseling, and treatment. Methods: We identified 7 patients with EC and a concurrent p53 FT signature. DNA extraction (Qiagen) from FFPE samples was performed and sent for whole genome sequencing (Novogene) on the paired FT and endometrial tissues to identify the specific p53 mutations. Using a position-wise comparison, we evaluated the clonal relationship between the specific p53 mutations identified in each pair. Results: In this cohort, 4 patients had endometrioid adenocarcinoma, 1 had mixed endometrioid and carcinosarcoma, 1 had high grade endometrial stromal sarcoma (ESS), and 1 had UPSC. All 7 patients had a p53 signature identified in the FT. Four patients had p53 overexpression while 3 had heterogenous p53 expression in the endometrium on IHC. Among the 7 patients, sequencing revealed 5 pairs with at least 1 shared somatic mutation identified in both the endometrium and FT. A shared mutation was identified in patients with carcinosarcoma, high grade ESS, UPSC, and two endometrioid adenocarcinomas. As of 9/2025 or last follow-up, no patients had developed a primary peritoneal malignancy, but 2 patients had disease recurrence. Both patients who had disease recurrence were among those with a shared somatic mutation identified. Conclusions: To our knowledge, this is the first study evaluating the relationship between concurrent FT p53 signatures and uterine cancer beyond serous. We identified 5 patients with at least 1 shared somatic p53 mutation. While these specific mutations have not been described as known pathogenic driver mutations in the literature to date, further exploration into these alleles is needed. A clonal relationship between FT lesions and endometrial cancer could have important implications on clinical counseling and management, thus further research into the specific p53 mutations identified and validation within a larger cohort is warranted.

Comparative efficacy and safety of first-line combination therapies with third-generation EGFR-TKIs in advanced <i>EGFR</i> -mutant NSCLC: A systematic review and network meta-analysis.

e20745 Background: While third-generation EGFR tyrosine kinase inhibitors (TKIs) are the standard first-line therapy for advanced EGFR-mutant non-small cell lung cancer (NSCLC), various combination strategies have been developed to overcome resistance and deepen responses. Direct comparisons between these strategies are lacking, leaving their relative efficacy and safety profiles undefined. Methods: We conducted a Bayesian network meta-analysis. Randomized controlled trials (RCTs) comparing five first-line strategies, third-generation EGFR-TKI monotherapy, or its combination with chemotherapy, anti-angiogenic agents, bispecific antibodies, or local consolidative therapy, were systematically searched in PubMed, Embase, and the Cochrane Library up to November 1, 2025. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), grade ≥3 adverse events (AEs), and overall survival (OS). Treatments were ranked using the surface under the cumulative ranking curve (SUCRA). Results: Nine RCTs (N = 2,750) were included. All combination strategies demonstrated superior progression-free survival (PFS) compared to TKI monotherapy. EGFR-TKI plus chemotherapy provided the most pronounced and consistent PFS benefit (HR 0.54, 95% CI 0.44–0.66) and achieved the highest surface under the cumulative ranking curve (SUCRA) value (0.8544) . A pairwise meta-analysis of available overall survival (OS) data also favored combination strategies (pooled HR 0.76, 95% CI 0.65-0.88) . In the OS subgroup analysis, patients aged under 65 years, harboring the 19del mutation, and with CNS metastases demonstrated significant differences. However, all combinations were associated with an increased risk of grade 3 or higher adverse events (AEs). Conclusions: For the first-line treatment of advanced EGFR-mutant NSCLC, combination strategies based on a third-generation EGFR-TKI improve PFS and show OS benefit compared to monotherapy. EGFR-TKI plus chemotherapy represents the current evidence-based benchmark for maximizing disease control. EGFR-TKI plus bispecific antibody emerges as a potent chemotherapy-sparing alternative with validated OS benefit. Treatment decisions require individualized calibration of the disease's aggressiveness against the patient's tolerance for increased toxicity.

Understanding patient priorities for survivorship care in older adults with cancer: A collaborative study by the Young Interest Group of the International Society of Geriatric Oncology.

e13789 Background: Integrating patient priorities into survivorship care for older adults with cancer is increasingly recognized as essential, yet little is known about how healthcare professionals (HCPs) across disciplines currently assess and incorporate these priorities into survivorship decision-making. We sought to assess HCPs' practices and contextual factors influencing the integration of patient priorities into survivorship care of older adults. Methods: This project, undertaken by the Young Interest Group of the International Society of Geriatric Oncology (YSIOG) Collaboratory Group, uses a mixed-methods, explanatory sequential design to understand how HCPs use patients’ priorities to guide survivorship care. In the quantitative phase of the study, from November 2025 to January 2026, we administered an international survey to HCPs through geriatric oncology networks—including Cancer and Aging Research Group (CARG) and International Society of Geriatric Oncology (SIOG)—and via national geriatric oncology representatives. Descriptive statistics summarize survey results, including participant characteristics, patterns across clinical roles, workflow practices, and perceived challenges. Results: Data were collected and analyzed from 178 HCPs practicing in 31 different countries. Respondents included oncologists/hematologists (69.5%), geriatricians (13.0%), nurses/nurse practitioners (9.2%), and other clinicians, with over half reporting &gt; 10 years of experience treating older adults. Nearly 90% currently provide survivorship care, most commonly managing late adverse events/toxicities (74%), conducting surveillance (71%), and addressing psychosocial concerns (48.9%). While 96.2% rated integrating patient priorities as “very” or “extremely important,” only 48.1% reported “often” or “always” discussing priorities during survivorship visits, and only 46% reported the utilization of formal tools to assess them (e.g. geriatric assessment, goal setting framework). Major barriers were time constraints (79.4%), lack of training (54%), system-level challenges (40.5%), and patient-related factors (31.0%). Facilitators included interdisciplinary teamwork (84.1%), institutional support (65.1%), use of structured tools (61.1%), and patient/caregiver engagement (70.6%). Conclusions: Clinicians across disciplines recognize the importance of integrating patient priorities into survivorship care, however, they face substantial workflow and system-level barriers. These preliminary results will be examined in a second phase of the study through qualitative interviews with HCPs to inform future implementation strategies focused on supporting priorities-aligned survivorship care.

Toxicity versus benefit: A prospective matched analysis of SBRT with vs without ADT.

e17115 Background: The survival benefit of adding androgen deprivation therapy (ADT) to radiotherapy for intermediate- and high-risk localized prostate cancer (PCa) was established in trials conducted before the widespread adoption of contemporary image guidance, hypofractionation, and stereotactic ablative radiotherapy (SABR). As SABR enables delivery of high biological doses with improved precision, the incremental oncologic contribution of ADT in the SABR era is increasingly uncertain. This question is particularly relevant for older patients, who frequently have comorbidities and competing mortality risks, where ADT-related sexual, metabolic, and quality-of-life toxicities may outweigh potential benefit and may plausibly worsen overall health status. Methods: We conducted a prospective matched cohort study of men with intermediate- and high-risk localized PCa treated with SABR (35 Gy in 5 fractions) with or without ADT between 2018 and 2024. For each patient receiving SABR+ADT, a contemporaneous SABR-alone patient was matched based on NCCN risk group, baseline PSA, age, and treatment year. Thirty-nine matched pairs were included; mean age was 70.6 years and median follow-up was 42 months. Biochemical recurrence (BCR) was defined per Phoenix criteria. Time-to-event outcomes were analyzed using Kaplan-Meier, log-rank, and stratified Cox models; toxicities were collected retrospectively from medical records. Results: BCR occurred in 5 patients treated with SABR+ADT and 4 patients treated with SABR alone. BCR-free survival did not differ significantly between groups (log-rank p = 0.13). In a stratified Cox model, omission of ADT did not increase the risk of BCR (HR 1.47; 95% CI 0.59–3.64; p = 0.41). Patterns of recurrence were similar across risk categories (HR: 3 vs 3; UIR: 2 vs 1). One SABR-alone patient developed a solitary bone metastasis that was successfully treated with ablative SABR. No prostate cancer-specific deaths occurred in either cohort. Unrelated mortality was 4 vs 2, and loss to follow-up was 4 vs 1 (ADT vs no ADT). Treatment-related toxicity was reported in 28/39 ADT-treated patients, including sexual dysfunction, fatigue, and metabolic adverse effects. No clinically meaningful toxicity was observed with SABR alone. Conclusions: In this prospective matched cohort of predominantly older men treated with SABR for intermediate- and high-risk localized PCa, omission of ADT was not associated with worse biochemical outcomes while avoiding substantial toxicity. Given the comorbidity burden and competing mortality risks common in this population, routine ADT use may represent avoidable harm for selected patients, whereas SABR alone may preserve cancer control with a more favorable tolerability profile. These findings support individualized, risk-adapted ADT use in the SABR era and justify larger prospective studies to refine patient selection.

Interlayer-dependent dual-mode response in OLED–UV photodetectors based on hybridized local and charge-transfer emitters

Dual-mode organic devices that combine organic light-emitting diodes (OLEDs) with reverse-bias ultraviolet organic photodetectors (UVOPDs) must improve emissive efficiency without unduly compromising photocurrent generation and dark-current suppression. Herein, we use established hybridized local and charge-transfer (HLCT) blue emitters as a controlled platform to examine how interlayers influence this trade-off within a shared OLED-like architecture. Among the three HLCT emitters investigated, the PyIAnp-based device provides the most favorable baseline combination of OLED efficiency and reverse-bias photodetection response, delivering a maximum external quantum efficiency (EQEmax) of 8.07%, a responsivity of 6.79 mA W−1, and a detectivity of 2.88 × 1011 Jones at −0.5 V. Upon introducing an interlayer, the device characteristics improve further; in particular, TAPC yields the best combined response, increasing EQEmax to 10.24% while reducing the dark current density to 2.59 × 10−10 A cm−2, enhancing the responsivity to 19.99 mA W−1, and increasing detectivity to 2.19 × 1012 Jones at −0.5 V. The photoluminescence quantum yield (PLQY) and time-resolved photoluminescence (TRPL) measurements are consistent with reduced interfacial loss and a more favorable excited-state relaxation environment after TAPC insertion. Preliminary operational stability was also observed under the tested OLED and OPD conditions. These results show that interlayer selection provides a useful means of tuning interfacial processes in integrated OLED-like devices with reverse-bias ultraviolet photodetection functionality.

PEG entrapped ZnO synthesized using Calendula officinalis flower extract- physicochemical characterization, in vitro and in vivo biocompatibility assessment, and antibiofilm activity