Browse Articles

REVO-U: A next-generation, gene-editing–free universal CAR-T platform to enable ultra–high-yield manufacturing and identification of early clinical activity in relapsed/refractory DLBCL.

7013 Background: We previously invented autologous CAR-T product ciltacabtagene autoleucel (Carvykti) for multiple myeloma, with robust efficacy. However, its personalized nature incurs high costs and limits scalability. Conventional universal CAR-Ts rely on complex gene editing, yielding 50-100 doses/batch, yet to be commercially approved. We created REVO-U, a gene-editing-free universal CAR-T platform using proprietary technologies, initiating explorations in hematologic and solid tumors. It enables >3,000 doses/single batch from healthy donor cells, reducing costs and potentially eliminating capacity constraints in cell therapy. Methods: REVO-U uses protein-directed degradation to mitigate GvHD without gene editing. In a single-arm, open-label exploratory study, CD19-targeted REVO-UWD19 was given post-lymphodepletion (fludarabine/cyclophosphamide) with short-term oral mycophenolate sodium (EC-MPS) in relapsed/refractory DLBCL patients. Results: Four subjects treated (see Table for details). Subject 1 (Flu 30/Cy 300 mg/m² + 100e6 cells; EC-MPS 1440 mg BID x5 days, MPA average AUC 22.12 mg·h/L): PK Cmax 4.3k copies/mL, Transient fever (38.5°C, grade 0 CRS); ≥PR ongoing >10 months. Subject 2 (Flu 30/Cy 400 mg/m² + 200e6 cells; EC-MPS 1440 mg BID x11 days, MPA average AUC 71.44 mg·h/L): Cmax 173.9 k copies/mL, grade 1 CRS, CMR by PET-CT (PFS 4 months). Subject 3 (73y, high burden; Flu 30/Cy 500 mg/m² + 200e6 cells; EC-MPS x14 days, MPA average AUC 71.23 mg·h/L): REVO-U CAR-T expansion was highly significant. Cmax reached 19,057.6 k copies/mL, grade 3 CRS/HLH (controlled), followed by prolonged neutropenia and a fatal infection; PR, unconfirmed CR. Subject 4 (post-DLT: Flu 30/Cy 400 mg/m² + 50e6 cells; EC-MPS x22 days, MPA average AUC 15.21 mg·h/L): Cmax 2.01 k copies/mL, No CRS, PD. No GvHD in any patient. The target effective MPA AUC is >30 mg·h/L. Only Subjects 2 and 3 achieved this threshold on average MPA exposure. Conclusions: REVO-U enables ultra-scalable manufacturing like biologic drugs. Early DLBCL data show no GvHD, with expansion, CRS and responses influenced by lymphodepletion, dose & MPA exposure. Timely EC-MPS adjustment per MPA AUC may be needed for efficacy assurance. Promising PK expansion, persistence post-EC-MPS withdrawal, and efficacy signals have also emerged in solid tumor target explorations. We will report updated data on this innovative universal platform across malignancies at future conferences. Clinical trial information: NCT06662227 . Summary of lymphodepletion, cell dosing, MPA exposure, pharmacokinetic, safety, and efficacy. Subject Flu/CTX Dose EC-MPS MPA-mAUC PK Cmax CRS DLT Efficacy PFS # (mg/m 2 (million cells) (Day used) (mg*h/L） (k Copies/mL） (Grade) (30 days) (months) 1 30/300 100 5 22.12 4.3 0 - PR (CR?) >10 2 30/400 200 11 71.44 173.9 1 - CMR 3 3 30/500 200 14 71.23 19057.6 3 + PR (CR?) 4 30/400 50 22 15.21 2.01 0 - PD

Persistent and divergent cervical cancer burden in Sub-Saharan Africa, 1990–2023.

e22588 Background: Cervical cancer is among the most preventable malignancies, yet sub-Saharan Africa (SSA) bears the highest global burden with substantial sub-regional heterogeneity often obscured by regional aggregates. Sub-regional analyses are needed to guide targeted interventions. Methods: Using Global Burden of Disease (GBD) 2023 data, we analyzed age-standardized incidence (ASIR), mortality (ASMR), and disability-adjusted life years (ASDALYR) per 100,000 people for cervical cancer from 1990–2023 across Central, Eastern, Southern, and Western SSA. Global rates were used as a comparator. Temporal trends were quantified using estimated annual percentage change (EAPC) with 95% confidence intervals. Results: In 2023, SSA maintained the highest global cervical cancer burden, with ASIR 55.9, ASMR 27.1, ASDALYR 1040.9, representing more than two- to four-fold global rates. Eastern SSA had the highest burden in 2023; ASIR increased to 78.7 (EAPC 0.37%; 0.22, 0.52) while ASMR of 37.0, and ASDALYR of 1470.6 were stable. Central SSA burden increased over time, ranking second in 2023 burden, with 2023 ASIR of 63.9 (EAPC 1.48%; 1.19, 1.77), ASMR of 31.4 (1.02%; 0.82, 1.22), and ASDALYR of 1228.9 (1.10%; 0.85, 1.35). Southern SSA, despite the lowest 1990 burden, had the steepest increases, with 2023 ASIR of 46.2 (2.67%; 2.39, 2.94), ASMR of 23.8 (2.19%; 1.93, 2.44), and ASDALYR of 825.3 (2.41%; 2.14, 2.68). In contrast, Western SSA had stable ASIR of 35.7 (−0.10%; −0.35, 0.15) alongside significant declines in ASMR 17.8 (−0.52%; −0.71, −0.32) and ASDALYR to 660.4 (−0.49%; −0.72, −0.26) with the lowest 2023 regional burden. Eswatini, Malawi, and Zambia are countries that had the highest cervical cancer burden and ranked first through third globally (ASIR/ASMR/ASDALYR: 157.6/69.4/2999.1; 135.9/60.0/2598.7; 112.6/55.9/2163.8). South Africa, Malawi, Namibia, the Democratic Republic of the Congo, and Lesotho experienced the largest increases in ASIR (EAPC 1.85−3.19%), ASMR (1.43−2.64%), and ASDALYR (1.48−2.89%); while Rwanda, Mozambique, Madagascar, Comoros, Nigeria, United Republic of Tanzania, and Burkina Faso exhibited the largest declines in ASIR (−0.41 to −1.75%), ASMR (−0.73 to −1.34%), and ASDALYR (−0.71 to −2.00%). Across all SSA regions, all rates showed a post-2020 uptick. Conclusions: Cervical cancer burden in SSA remains the highest globally and is highly heterogeneous, likely reflecting sub-regional differences in HIV burden, HPV vaccination and screening coverage, and health-system capacity. While Western SSA demonstrates progress, rising burden in Central, Eastern, and Southern SSA coupled with post-2020 upticks across regions, underscore persistent gaps in HPV vaccination, screening, and treatment access. Accelerated, region-specific implementation of comprehensive prevention and screen-and-treat strategies is urgently needed to advance cervical cancer elimination goals.

Racial and rural-urban disparities in radiotherapy utilization for oral cavity and pharyngeal cancers: A SEER analysis from 2013-2022.

e18101 Background: Head and neck cancers accounted for 1,464,550 new cases and 487,993 deaths across the world in 2020 and 51,127 new cases in the United States in 2022. A key therapy for these cancers involves radiation therapy, either as sole therapy for early-stage tumors or in combination with surgery or chemotherapy for advanced stage disease. Unfortunately, numerous barriers exist to accessing care for patients requiring radiation. Rural areas face higher cancer and risk factor incidence and mortality rates compared to urban areas, while facing unique challenges (lower educational attainment, difficulties with transportation). In this abstract we explore racial trends and disparities in radiotherapy utilization for oral cavity and pharyngeal cancers across the U.S. Methods: We conducted a population-based cohort study of radiotherapy utilization across racial groups and rural-urban residence over the period 2013-2022. We queried the National Cancer Institute Surveillance, Epidemiology and End Results Program (SEER) for diagnoses of head and neck cancer (Oral Cavity and Pharynx, based on ICD-O-3 sites). Using year of diagnosis as a continuous variable, radiotherapy utilization was modeled as a binomial outcome (received vs did not receive). Multivariable logistic regression was performed to evaluate association between radiotherapy utilization and race, rural-urban residence, and year of diagnosis. Interaction terms were introduced to evaluate effect modification by geography. The reference cohort was Non-Hispanic White. Results: A total of 187,457 Oral cavity and Pharyngeal cancers were included, of which 113,624 utilized radiation therapy while 73,833 did not. 162,717 were urban and 24,740 were rural residents. Radiotherapy utilization declined significantly over time from 2013 to 2022 (-0.7% per annum, OR 0.99 per year, p<0.001). Rural residence was independently associated with lower odds of radiotherapy utilization (OR 0.96, p<0.05). Non-Hispanic Black patients had higher odds of utilization (OR 1.19, P<0.001). While no significant differences were observed for Non-Hispanic Asian/Pacific Islander or American Native/Alaskan patients, significant effect modification by geography was seen for Hispanic patients in rural areas, indicating lower radiotherapy utilization (OR 0.82, p = 0.024). Conclusions: Radiotherapy utilization remains low in rural areas with a concerning declining trend overall. Hispanic race demonstrates geography-specific disparity between rural and urban populations, indicating possible unique barriers to care. While Non-Hispanic Black patients demonstrated significantly higher odds of radiotherapy receipt, non-significant trends towards attenuation were noted, with a significant utilization decline for Non-Hispanic Native American/Alaskan patients indicating worsening disparity over this period.

Defining a long-term benefit phenotype to PD-1 inhibitors in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): A multicentre retrospective study.

6050 Background: Limited data exists on predictors of durable benefit to PD-1 inhibitors in R/M HNSCC. We aimed to identify clinical characteristics associated with long-term benefit from anti-PD-1 therapy in R/M HNSCC. Methods: We reviewed clinical data from patients with R/M HNSCC treated with PD-1 inhibitors between December 2018 and August 2025, at Princess Margaret Cancer Centre (an academic hospital) or within the William Osler Healthy System (a community hospital). Eligible patients received pembrolizumab or nivolumab, either alone or with chemotherapy (for pembrolizumab), and had available tissue for planned biomarker studies. Patients were grouped by progression-free survival (PFS): (A) PFS ≥ 24 months (m), (B) PFS 12-24 m and (C) best response of progressive disease (PD). Best response was determined from treating physician documentation based on clinical and radiographic assessment. PFS was estimated with the Kaplan-Meier method. Univariate analysis used Kruskal-Wallis test for continuous variables and Fisher’s exact or Chi-square tests for categorical variables. Results: A total of 150 patients were included: 31 in group A (PFS ≥ 24 months), 28 in group B (PFS 12-24 months) and 91 in group C (PD as best response). We observed significantly more immune-related adverse events (irAEs) (61% vs 16%, OR 8.0, 95% CI 3.2-19.9, p<0.001) and corticosteroid use (32% vs 8.8%, OR 4.9, 95% CI 1.7-14.1, p= 0.002) in group A compared to group C. There was a trend toward a higher proportion of patients with lung-only metastases in group A compared to C (39% vs 21%, OR 2.4, 95% CI 1.0-5.8, p= 0.052). Similar associations were found for irAEs (p<0.001), corticosteroid use (p= 0.011) and lung-only metastases (p= 0.054) in group B compared with group C. Additionally, we found more active smokers (p=0.010) and ex-smokers (p= 0.036) in group B compared to group C, as well as more active smokers in group B compared to group A (p= 0.042), whereas smoking rates were similar in groups A and C. Interestingly, there was no significant difference in Charlson Comorbidity Index (CCI) scores, albumin levels or neutrophil-to-lymphocyte ratios (NLR) between the three groups. The mean CCI scores were 7.3, 7.3 and 7.1; albumin levels 39.1, 40.1 and 39.7 and NLR 6.8, 6.5 and 8.7 for groups A, B and C respectively. P16 status and PD-L1 CPS were distributed similarly between the groups, although PD-L1 testing was not available in 25% of patients. Conclusions: IrAEs, corticosteroids and lung-only metastases are associated with PFS ≥ 12 m in patients with R/M HNSCC treated with anti-PD-1 agents. Smoking is associated with PFS 12-24 m but not with PFS ≥ 24 m, suggesting a potential role in acquired resistance. Further molecular analysis in this population is underway to identify biomarkers of long-term benefit.

Reevaluating the comparative effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RA) vs aspirin for colorectal cancer prevention in type 2 diabetes.

e15690 Background: Recent studies suggest that aspirin and GLP-1RA may reduce the risk of colorectal cancer (CRC). A recent presentation reported a substantially greater primary preventive effect of GLP-1RA compared with aspirin, with an estimated 36% risk reduction. However, this analysis excluded patients using NSAIDs and other anti-diabetic medications, despite GLP-1RAs being predominantly prescribed for type 2 diabetes (T2D) and commonly used in combination with agents such as metformin. We therefore re-evaluated CRC risk among GLP-1RA and aspirin users with T2D, adjusting for background anti-diabetic therapies and other key covariates. Methods: We utilized the TriNetX Global Collaborative Network, a de-identified electronic medical record database encompassing over 160 institutions worldwide, to identify patients with T2D between 2010 and 2023. Two mutually exclusive cohorts were defined: patients using any GLP-1RA without aspirin (GLP-1RA cohort) and patients using aspirin without any GLP-1RA (aspirin cohort). Patients with a prior history of CRC or benign colorectal neoplasms were excluded. Propensity score matching was performed on demographics, comorbidities, laboratory values, including HbA1c, BMI, and medications, including background anti-diabetic therapies. The index date was defined as the first recorded use of GLP-1RA or aspirin. Cox proportional hazards models were used to estimate hazard ratios (HRs) for CRC risk. Results: After PSM, 402,661 patients were included in each cohort. Baseline characteristics were well balanced, with a mean age of 57 years, 62% White, and 57% female. Anti-diabetic regimens were also well matched: 50% of patients in each cohort used metformin, 19% sulfonylureas, 11% SGLT2 inhibitors, 12% DPP-4 inhibitors, and 34% insulin. BMI remained higher in the GLP-1RA cohort compared with the aspirin cohort (36.1 vs 34.1) after matching. Mean follow-up was shorter in the GLP-1RA cohort (1,100 days) than in the aspirin cohort (1,530 days). CRC occurred in 0.2% (884/402,661) of patients in the GLP-1RA cohort and 0.3% (1,209/402,661) in the aspirin cohort; however, these crude incidence differences reflect unequal follow-up duration between cohorts. In Cox regression analysis accounting for time-to-event, there was no significant difference in CRC risk between cohorts (HR 1.018, 95% CI 0.932–1.112, p = 0.693). Results remained non-significant at 5-year (HR 1.003, 95% CI 0.912–1.104, p = 0.945) and 10-year follow-up (HR 0.971, 95% CI 0.890–1.059, p = 0.504). Conclusions: Among patients with T2D, when NSAID use and background hypoglycemic medications were not excluded and anti-diabetic therapies were matched, GLP-1RA use was not associated with greater CRC risk reduction compared with aspirin. Given the inherent limitations of retrospective analyses, prospective studies are warranted.

Comparison of baseline gut microbiome features between response subgroups of patients (pts) with advanced melanoma undergoing immune checkpoint inhibitor (ICI) therapy.

9528 Background: Gut microbiome composition has been implicated as a potential biomarker of response to ICIs in melanoma pts, but it is unclear whether baseline gut microbiome composition may predict emergence of specific ICI resistance subtypes (primary vs. acquired resistance) or immune-related adverse events (irAEs). We sought to define clinical characteristics and baseline gut microbiome features that correlate with ICI resistance subtypes and irAEs in melanoma pts. Methods: We identified 90 pts from our institution’s fecal biorepository of advanced melanoma pts who received ICIs and who had ≥ 1 pre- or on-treatment fecal sample available for 16S rRNA amplicon sequencing. Pts were categorized into 3 responder subgroups: responder (R, no progression on ICI), primary resistance (pR, progression < 6 months from ICI start), or acquired resistance (aR, progression ≥ 6 months from ICI start). Associations between clinical covariates and survival were analyzed using Kaplan-Meier and Cox proportional hazards models. Microbial features were compared using alpha and beta diversity metrics and pairwise comparisons at each taxonomic level using Wilcoxon rank-sum tests. Results: Baseline demographic and clinical characteristics were similar between subgroups (R, n = 35; pR, n = 32; aR, n = 23). IrAE occurrence rates significantly differed between responder subgroups (p = 0.048). Pts who developed irAEs had significantly longer progression-free survival (PFS) than those without irAEs (median PFS 1412 vs. 106 days, p = 0.026). Later treatment line and receipt of prior ICI were associated with significantly higher hazard ratios (HRs) for death and progression, while resectable disease and development of any-grade irAE were associated with lower HRs for death and progression. There was no significant difference in baseline alpha diversity between responder subgroups or irAE groups. A trend toward differences in baseline beta diversity between responder subgroups was observed (p = 0.084). Abundance of Faecalibacterium prausnitzii , a known butyrate producer, was significantly higher in R than pR (p < 0.001, p adj = 0.029), aR than pR (p < 0.001, p adj = 0.071), and in pts who did not develop irAEs (p = 0.02). Other operational taxonomic units more abundant in responders (aR vs. pR, R vs. aR/pR) and pts who did not develop irAEs include the short-chain fatty acid (SCFA) producers Coprococcus comes , Dorea longicatena , and Blautia glucerasea (p < 0.001, p adj = 0.071). Conclusions: Although no significant differences in baseline alpha diversity were observed between responder subgroups or irAE groups, responders and those without irAEs had significantly higher levels of SCFA-producing taxa at baseline, suggesting a potential immunomodulatory role for SCFAs such as butyrate in mediating ICI response and protection from irAEs.

Penpulimab (AK105) combined with cetuximab as first-line treatment in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): A phase II clinical trial.

6029 Background: Combination therapy with PD-1 and EGFR inhibitors has shown promising efficacy in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). This open-label, single-arm, multicenter phase II study aimed to evaluate the efficacy and safety of penpulimab (an anti-PD-1 monoclonal antibody) plus cetuximab as first-line treatment in this patient population (NCT05260671). Methods: Eligible patients had R/M HNSCC with no prior immunotherapy or EGFR inhibitor exposure. Participants were either treatment-naïve for systemic therapy or had received platinum-based neoadjuvant/adjuvant or chemoradiotherapy more than 6 months before enrollment. All patients received cetuximab 500 mg/m² intravenously as a lead-in dose on day –14, followed by cetuximab 500 mg/m² plus penpulimab 200 mg intravenously on days 1 and 15 of each 28-day cycle. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between March 15, 2022, and January 19, 2026, 31 patients were enrolled. The median follow-up was 20.13 months (95% CI: 15.6–NA). Of these, 29 patients were evaluable for efficacy. The ORR was 44.8% (13/29), and the DCR was 82.8% (24/29). Four patients (13.8%) achieved a complete response (CR). The median DOR was 12.1 months (95% CI: 6.13–NA). For the entire cohort, median PFS was 6.0 months (95% CI: 4.3–18.3), with a 12-month PFS rate of 35.6%. Median OS was 29.1 months (95% CI: 18.2–NA), and the 12-month OS rate was 72.4%. Treatment-related adverse events (TRAEs) occurred in 29 patients (93.5%). Grade ≥3 TRAEs were observed in 4 patients (12.9%), including acneiform rash (6.5%), anemia (3.2%), and oral mucositis (3.2%). No fatal TRAEs were reported. Conclusions: The combination of penpulimab and cetuximab demonstrated favorable clinical efficacy and a manageable safety profile in patients with R/M HNSCC, supporting its potential as a first-line treatment option. Trial Registration: NCT05260671. Ethics Approval: This study was approved by the Ethics Committee for Drug Clinical Trials of the Eye & ENT Hospital of Fudan University (Approval No. [20211141-1], 2022). All participants provided written informed consent prior to enrollment. Clinical trial information: NCT05260671 .

Paired urine and plasma ctDNA profiling to enable longitudinal molecular monitoring during HER2 ADC bladder preserving therapy in muscle-invasive bladder cancer (HOPE03).

e16608 Background: Although trimodal therapy is the standard organ-preserving approach for muscle-invasive bladder cancer (MIBC), outcomes remain suboptimal, underscoring the need for noninvasive biomarkers to guide real-time decisions. We evaluated a bladder-sparing regimen of HER2 ADC plus PD-1 antibody and radiotherapy in localized HER2-positive MIBC, using NGS-based liquid biopsy to longitudinally track molecular dynamics in paired urine and plasma. Methods: HOPE03 is a multicenter, open-label, single-arm phase Ib/II trial (ChiECRCT20210564) enrolling patients with pathologically and radiographically confirmed HER2-positive MIBC. Patients received disitamab vedotin (RC48) in combination with toripalimab and radiotherapy. In this exploratory biomarker analysis, paired urine and plasma samples were collected serially from baseline through neoadjuvant treatment, radiotherapy, and follow-up to evaluate longitudinal molecular response. Tumor fraction and somatic alterations in circulating tumor DNA (ctDNA) and urinary tumor DNA (utDNA) were quantified using the PredicineCARE targeted NGS assay. Results: In the study cohort, 21 patients were eligible for NGS testing, of whom 18 had paired baseline urine and blood samples available. At baseline, urine demonstrated a substantially higher mutational burden than blood (246 vs. 41 mutations), with partial concordance between compartments (26 shared mutations). The most frequently altered genes in urine were TP53 (50%), TERT (44%), ARID1A (33%), KDM6A (33%), and RB1 (33%). In plasma, the most prevalent alterations were TP53 (33%), ATM (11%), BRAF (11%), BRCA2 (11%), and PIK3CA (11%). Baseline genomic alterations in both urine and blood were associated with clinicopathologic features. Patients harboring RB1 alterations in urine had significantly larger baseline tumor size (p = 0.012), and baseline tumor size was also significantly larger in patients with plasma ATM (p < 0.001), RB1 (p < 0.001), or TP53 (p = 0.009) alterations. Plasma TP53 alterations were additionally associated with higher Ki-67 levels (p = 0.009). Older age correlated with higher tumor fraction in both urine (p = 0.011) and plasma (p = 0.002). Notably, plasma PIK3CA alterations were associated with inferior progression-free survival (median PFS 9.3 months vs. not reached; p = 0.011). Conclusions: Serial NGS profiling of paired urine and plasma in HOPE03 demonstrated the feasibility of noninvasive molecular monitoring during RC48 plus toripalimab and radiotherapy for localized HER2-positive MIBC. These findings support integrated urine–plasma liquid biopsy as a tool for longitudinal response assessment and risk stratification in bladder-preserving therapy, warranting validation in larger prospective cohorts. Clinical trial information: ChiECRCT20210564.

Development of payload-resistant human ovarian cancer cell lines to better understand antibody-drug conjugate sequencing and resistance mechanisms.

5549 Background: Within gynecologic oncology, limited data exist regarding mechanisms of resistance to antibody-drug-conjugates (ADC) or the impact on response to future ADC treatment. The purpose of this study was to develop and characterize payload-resistant human ovarian cancer cell lines, and to determine the effect of payload resistance on subsequent ADC exposure. Methods: Three commercially available human high grade serous ovarian cancer cell lines (PEA1, PEA2, and OVCAR8) were each exposed separately to three commercially available payloads with corresponding, clinically approved ADCs (deruextecan/trastuzumab deruxetecan, SN38/sacituzumab govitecan, and DM4/mirvetuximab soravtansine). Cell viability assays were performed to confirm and quantify resistance after completion of treatment for payload-resistant cell lines, and western blot analyses performed to evaluate changes in HER2, TROP2, and FOLR1 expression between payload-resistant cells and their controls. Lastly, paired payload-resistant and -sensitive cell lines were then exposed to ADCs with different payloads for 48 hours, and cell viability assays were performed. Results: The development of payload-resistant cell lines demonstrates notable variability in timelines for attaining resistance, both across the three cell lines and within individual cell lines across different payload exposures. Compared to payload-sensitive controls, payload-resistant cells displayed similar morphologic changes including increased surface area; however, demonstrated variable differences in HER2, TROP2, and FOLR1 protein expression. Additionally, different payload-resistant cell lines responded differently to subsequent ADC exposure. As a specific example, DM4-resistant PEA1 cells were more sensitive to subsequent exposure to sacituzumab govetecan compared to DM4-senstive controls at various doses (p < 0.0001, see Table). Conclusions: This study illustrates challenges in developing payload-resistant cell lines, and highlights variability in molecular changes with payload resistance. The data demonstrate subsequent ADC susceptibility in some payload-resistant cell lines, highlighting the complexities of changes that occur with drug treatment. Our data suggests that HGSOC patients that received mirvetuximab soravtansine may be more susceptible to future treatment with sacituzumab govitecan. Future work is underway to expand these findings to determine ideal sequencing of these different ADCs, and to determine other off-target effects that may influence non-ADC treatment response. Viability of DM4-resistant versus sensitive PEA1 human ovarian cancer cells after exposure to sacituzumab govitecan (SG). DM4 resistant Control Average % viability SEM Average % viability SEM p value SG 400nM 52.01 1.63 98.98 1.01 < 0.000001 SG 600nM 45.43 0.65 96.87 0.49 < 0.000001

A preventable cancer with unequal outcomes: Cervical cancer disparities in Wisconsin, 2014–2021.

e22595 Background: Cervical cancer remains a preventable cause of morbidity and mortality in the United States, with available vaccination and screening modalities. However, nationally, disparities in outcomes persist across racial and socioeconomic groups. In Wisconsin, these disparities have been insufficiently characterized. Detailed local data is needed to inform policy, planning, and targeted intervention. As such, our study aims to evaluate cervical cancer metrics across race, ethnicity, socioeconomic indicators, and geography using statewide registry data. Methods: Our study utilizes Wisconsin Cancer Reporting System (WCRS) data from 2014–2021. Descriptive statistics summarized demographics and clinical characteristics. Age-adjusted statewide incidence rates were calculated. Cox proportional hazards models examined predictors of cervical cancer survival. Neighborhood-level poverty (American Community Survey) and Rural-Urban Community codes (United States Department of Agriculture) were linked using patient census tract data. Adaptive spatial filtering was used to map geographic variation in cervical cancer incidence across Wisconsin. Results: A total of 1,429 cases were identified in Wisconsin from 2014–2021. Incidence was highest among Black (80.1) and Hispanic (73.0) women, compared with White women (45.7 per 100,000). The median age at diagnosis was 50 years, with Hispanic patients diagnosed at a younger median age of 43 years. Black patients resided in tracts with higher mean poverty (24.9%) than white (8.4%) patients. In Cox models, patients insured primarily by Medicaid (HR = 1.71, p = 0.005) and Medicare (HR = 2.34, p < 0.001) succumbed to cervical cancer earlier than those privately insured. Spatial analyses demonstrated elevated incidence in southern urban areas and northeastern regions of Wisconsin. Conclusions: Marked disparities in cervical cancer incidence and survival persist in Wisconsin. These findings underscore the need for targeted screening, early detection, and care navigation efforts to improve outcomes across populations.

Metformin use and outcomes among breast cancer patients on immunotherapy: Insights from a real-world cohort.

e23086 Background: An obesity-related cancer, 1 in 3 adults with breast cancer have preexisting type 2 diabetes (T2D) at diagnosis. Preclinical studies suggests that metformin, the most widely prescribed first-line therapy for T2D, may enhance response to PD-1 immune checkpoint blockade (ICB) by reducing immunosuppression, inhibiting tumor metabolism through AMPK signaling, and improving CD8⁺ T-cell and NK cell function within the tumor microenvironment. However, real-world evidence on anti-diabetic medication use in breast cancer patients with T2D receiving immunotherapy is limited. We sought to determine if metformin use is associated with improved overall survival (OS) in adults with T2D and breast cancer receiving ICB. Methods: TriNetX is a federated data network that aggregates electronic health record data across 44 healthcare organizations (HCOs) and links to insurance claims and mortality registries. Within the TriNetX Linked Network, we identified females with breast cancer and T2D who received ICB (pembrolizumab) for their breast cancer between 1/01/2021-12/01/2025. Our primary outcome was OS defined as time from pembrolizumab initiation to death and our key explanatory variable was metformin use (yes/no). We employed Cox proportional hazards models, including age, comorbid conditions, prior and concurrent cancer and diabetes treatments, to evaluate the association between metformin use and OS, overall, and for stage I-III vs. metastatic breast cancer (mBC) patients, and with time to next line of therapy (LOT) for mBC patients. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated for all estimates. Results: Our analytic cohort included 1,101 females with breast cancer and T2D who received pembrolizumab. Mean age was 58.2 (SD 11.5) years, 40.0% were obese (BMI > 30), 51.7% had hyperlipidemia, 65.7% had hypertension, and 47.7% had metastatic disease at pembrolizumab initiation. Overall, 23.6% (260/1101) were taking metformin with a mean 5.2-year (SD 3.9) history of metformin use at baseline. Over a median follow-up of 542 days (IQR = 249.0-915.0), we observed 203 deaths (Figure 1). In multivariable models, metformin was suggestively associated with improved OS (aHR 0.71; 95% CI 0.50-1.02, p = 0.059) in the total cohort, and among mBC patients (aHR 0.64; 95% CI 0.40-1.02, p = 0.058). Within the mBC group, 72/525 progressed to another LOT after pembrolizumab, and patients taking metformin had 57% lower risk of progressing to a new LOT during follow-up (aHR = 0.43, 95% CI 0.20-0.90, p = 0.015). Conclusions: In this real-world cohort of 1101 adults with T2D and breast cancer treated with pembrolizumab, metformin use was associated with improved outcomes among individuals with metastatic breast cancer. Prospective studies with larger sample sizes and longer follow-up periods are needed to confirm our findings.

Biofabrication, characterization, and efficacy of copper oxide nanoparticles derived from Caesalpinia bonducella Linn. in combating breast cancer

Solid–Liquid Synergy Enables a Trisulfur‐Radical‐Rich Microenvironment for Accelerated Li–S Conversion Kinetics

ABSTRACT Understanding and regulating the rate‐determining steps (RDSs) of lithium–sulfur batteries (LSBs) is crucial for enhancing their electrochemical performance. Herein, we propose a synergistic strategy that integrates a template sulfur host containing oxygen vacancies with a high‐donor‐number (high‐DN) solvent as an additive of the traditional ether‐based electrolyte. The strategy establishes a localized high‐DN microenvironment with a significant concentration of trisulfur radicals on the cathode side. Both experiments and calculations confirm that trisulfur radicals serve as key mediators in accelerating the RDS from the intrinsically sluggish quasi‐liquid–solid reaction to the more kinetically favorable trisulfur radicals‐mediated conversion. Benefiting from the RDS enhancement mediated by trisulfur radicals, the LSB maintains an 85.4% capacity after 500 cycles at 1 C, with an average decay rate of only 0.03% per cycle. In addition, an initial capacity of 659.6 mAh g −1 is achieved at 5 C or 1126.9 mAh g −1 at a high sulfur loading of 4.6 mg cm −2 . This work presents a novel trisulfur radicals mediated‐catalytic mechanism and breaks the limitations of the intrinsic RDS through integration of interface engineering and electrolyte modulation.

A phase 1a/b study of RGT-61159, an oral MYB splicing modulator, in patients with advanced adenoid cystic carcinoma and colorectal cancer.

3089 Background: MYB is a master regulator of cell proliferation, self-renewal, and differentiation processes and its aberrant expression is found in multiple forms of human cancer including adenoid cystic carcinoma (ACC), acute myeloid leukemia, T-cell acute lymphoblastic leukemia, colorectal cancer (CRC), small cell lung cancer, and breast cancer. RGT-61159 is an orally available small molecule designed to selectively modulate splicing of the oncogenic transcription factor MYB, resulting in downregulation of MYB protein levels and tumor cell death. Methods: This ongoing Phase 1a/b, multi-center, open-label clinical trial evaluates RGT-61159 in patients (pts) with advanced, relapsed or refractory ACC or CRC. Pts with ACC must have disease progression within 12 months of study entry. The study employs a 3+3 dose-escalation design with daily oral dosing in 21-day cycles, starting at 6 mg and escalating using a Fibonacci scheme. Primary objectives are to assess safety and tolerability and determine the recommended Phase 2 dose (RP2D). Secondary objectives include characterization of pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity. Results: As of 22 December 2025, 44 pts (86% ACC, 14% CRC) were treated across 8 dose levels (6–144 mg). In pts with ACC, median age was 61 years (range: 33–77) and median prior lines of therapy was 1 (range: 0-6); 47% were female. In pts with CRC, median age was 63 years (range: 44–72) and median prior lines of therapy was 5.5 (range: 4-8); 50% were female. Dose-limiting toxicities (DLTs) occurred in three pts: G3 nausea and muscle weakness, G3 fatigue, and missed doses due to G2 atrial flutter. Treatment-emergent adverse events (TEAEs) observed in ≥20% of pts were diarrhea, nausea, fatigue, dyspnea, and anemia. One G3 vasculitis (144 mg) and dose-related inflammatory edema events (G2 at 108/144 mg; G1 at lower doses) occurred; none were protocol-defined DLTs. Overall, RGT-61159 was well tolerated at or below the provisional RP2D of 84mg. 19 pts remain on treatment, including 9 pts (all with ACC) treated from 24 to 60mg who have been on study for more than 6 months with durable stable disease. In 35 evaluable pts, 18 have had tumor regressions with one partial response (RECIST v1.1) observed in a pt with ACC treated at 60mg. After the data cut, another pt with ACC treated at 84mg also achieved a partial response. Dose-dependent, robust knockdown of MYB in the peripheral blood was observed (up to 75% at 84mg). Plasma exposure increased approximately dose-proportionally with low to moderate variability. Conclusions: RGT-61159 is well tolerated at doses at or below the provisional RP2D. Robust peripheral knockdown of MYB was observed in a dose-dependent fashion at clinically relevant doses. Clinical activity manifested as prolonged stable disease and a partial responses primarily in pt with ACC. Clinical trial information: NCT06462183 .

A phase 1 study of BGB-B2033 (GPC3 x 4-1BB bispecific antibody) monotherapy in patients with selected advanced or metastatic solid tumors: First disclosure of clinical data.

3016 Background: GPC3 is a tumor-specific antigen that is highly expressed in hepatocellular carcinoma (HCC) and squamous non-small cell lung cancer. 4-1BB is a co-stimulatory receptor on activated T cells that promotes proliferation, survival and cytolysis of T cells. BGB-B2033, a novel, IgG-based GPC3 x 4-1BB bispecific antibody with Fc region engineered to prevent FcγR binding and increase half-life, activates T cells while minimizing systemic toxicity. BGB-B2033 is being studied as monotherapy or in combination in patients (pts) with advanced GPC3-expressing solid tumors in a first-in-human phase 1 trial (NCT06427941). Here we report initial results from the monotherapy dose escalation and safety expansion (part A). Methods: In part A, eligible pts with ≥1 prior systemic therapy received ascending dose levels of BGB-B2033. The primary objective was safety. Secondary objectives were preliminary antitumor activity (per investigator-assessed RECIST v1.1), pharmacokinetics, and immunogenicity. Dose escalation followed the Bayesian mTPI-2 design. Results: As of December 10, 2025, part A enrolled 61 pts; 60 (98.4%) had HCC and 56 (91.8%) were Asian. Median (range) prior lines of therapy were 2.0 (1-6). The median (range) study follow-up was 3.9 (0.3-14.9) months. Treatment-emergent adverse events (TEAEs) were reported in 63.9% of pts across the 8 dose levels; 27 (44.3%) pts had treatment-related (TR)-TEAEs. Six grade ≥3 TR-TEAEs occurred in 5 (8.2%) pts: alanine aminotransferase (ALT) increased, aspartate aminotransferase increased, blood bilirubin increased, drug eruption, lymphopenia and neutrophil count decreased (1.6% each). One dose-limiting toxicity (ALT increased) resolved after dose reduction. Immune-mediated adverse events (imAEs) were reported in 4 (6.6%) pts; all were grades 1-2. One pt reported a grade 1 infusion-related reaction. In the 59 efficacy-evaluable pts with HCC, confirmed ORR was 20.3% (95% CI: 11.0-32.8), with 12 partial responses; 23 pts had stable disease, 23 had progressive disease, and 1 pt was not evaluable. Ten of the 12 responders had ongoing response at data cutoff. A preliminary dose response was observed; at doses above the predicted target efficacious dose, confirmed ORR was 28.9% (11/38). Serum concentration profiles of BGB-B2033 exhibited target-mediated drug disposition at lower dose levels and decreased in a more biexponential manner at higher dose levels. Soluble 4-1BB, a pharmacodynamic marker, showed a greater increase at higher dose levels. Conclusions: BGB-B2033 was generally well tolerated, with limited imAEs in this predominantly 2L+ HCC population. Durable responses were observed in pts with advanced HCC, including pts with prior PD-(L)1-based treatment. Triplet dose escalation with tislelizumab and bevacizumab as well as monotherapy dose expansion are ongoing. Clinical trial information: NCT06427941 .

Remote physical activity intervention for young Hispanic breast cancer survivors with persistent post-surgical pain.

e12699 Background: Young breast cancer survivors frequently experience persistent post-breast surgery pain syndrome (PBSPS) during periods of active employment, caregiving, and recovery, leading to barriers in participating with in-person physical activity and therapy programs. We evaluated the feasibility and acceptability of a remotely delivered, physical activity intervention using health coaching calls for young Hispanic breast cancer survivors with PBSPS. Methods: We conducted a single-arm, 12-week pilot study enrolling self-identified Hispanic women younger than 60 years old, at least 3 months post-treatment for invasive breast cancer or ductal carcinoma in situ, who reported persistent post-surgical pain. The intervention included a Fitbit activity tracker and bi-weekly health coaching calls with motivational interviewing. The program emphasized whole-of-day movement to increase physical activity and reduce sedentary behavior. Feasibility outcomes included recruitment, retention, and adherence. Exploratory outcomes assessed changes in pain interference (0-10 scale) and bodily monitoring (0-24 scale) and bodily threat appraisals (0-52 scale). Results: Twenty-five breast cancer survivors enrolled (mean age 47.4 years [SD 6.3]), with 71% selecting Spanish-language intervention delivery. Of these, 56.5% were early stage at diagnosis and on average 3.78 [SD 2.89] years since surgery. Retention at 12 weeks was 76% (19/25). Engagement with health coaching was high, with 95% completing at least four of five scheduled calls. There was a suggested 0.7 to 1.7 point decrease in pain interference across daily activities, sleep, mood, and stress (p-values > 0.05, except for stress). While there was minimal change in bodily monitoring (-2.4 points), there was a decrease of (-6.1 points) on bodily threat appraisals. Conclusions: A remotely delivered, health coaching based physical activity intervention is feasible and acceptable for young Hispanic breast cancer survivors with PBSPS. These findings support further evaluation in a randomized controlled trial and emphasize the importance of accessible, flexible survivorship interventions for younger breast cancer patients in their preferred language. Clinical trial information: NCT06260332 .

A phase I/II study of safety/efficacy using lurbinectedin, combined with ipilimumab, and nivolumab, for advanced soft tissue sarcomas (NCT05876715).

TPS11599 Background: Soft tissue sarcoma (STS) cells exhibit heightened immunogenicity during the early stages of the disease. Therefore, immunotherapies such as ipilimumab (ipi) and nivolumab (nivo), which enhance sustained T-cell activation by suppressing regulatory T cells, are potentially more effective when administered as first-line therapy in combination with lurbinectedin—a synthetic analog of the marine alkaloid trabectedin—that not only induces apoptosis in cancer cells and exposes tumor neoantigens for immune recognition but also depletes tumor-associated macrophages, thereby restoring immune surveillance and potentially enhancing the efficacy of immunotherapy. Methods: This Phase I/II open-label single-site study will evaluate the safety and efficacy of lurbinectedin in combination with ipi and nivo in patients with advanced STS. Phase I patients will be previously treated, whereas phase II patients will be untreated. Objectives: Primary: Evaluate MTD of lurbinectedin in combination with fixed doses of ipi and nivo. Secondary: Evaluate objective response rate by RECIST v1.1 via CT/MRI/PET q 6w until end of treatment (EOT); determine progression-free survival (PFS); determine overall survival (OS). Exploratory: correlate response with amount of ctDNA via Signatera testing q 6w until EOT. Schedule: IV lurbinectedin q 3w (Phase I: escalating doses as per standard “cohort of three” design, 2.6 - 3.2mg/m2, Phase 2: determined MTD), IV ipi 1 mg/kg q 12w, and IV nivo 3 mg/kg q 2w. Participants may continue treatment until significant disease progression or unacceptable toxicity occurs. Key Criteria: Inclusion: pathologic diagnosis of locally advanced unresectable or metastatic STS; measurable disease by RECIST v1.1; ECOG ≤ 1; life expectancy of ≥ 3 months; acceptable hematological status and liver/renal function. Exclusion: untreated CNS metastases; radiation therapy, targeted therapy, other antitumor treatment, or investigational drug or device study, within 2 weeks prior to study entry; chemotherapy within 21 days prior to study entry; prior exposure to anti-CTLA4 or anti-PD-1 inhibitors; pregnancy or breastfeeding; autoimmune disease, carcinomatous meningitis, systemic immunosuppression, skin rash affecting > 25% of body surface area, or inflammatory bowel disease. Analysis: The Intention-To-Treat population (all patients who received at least one dose of study drug) will be used for OS analysis and adverse event analysis. The Modified Intention-To-Treat population (patients who completed the first two 3-week cycles and follow-up imaging) will be used for analysis of PFS. PFS and OS will be estimated by Kaplan Meir method with two-sided 95% confidence interval. Status: This study has enrolled 40 patients. Clinical trial information: NCT05876715 .

Comparative effectiveness of first-/second-generation EGFR-TKI combination therapy versus third-generation EGFR-TKI monotherapy in previously untreated advanced <i>EGFR</i> -mutant NSCLC: A real-world, retrospective study in China.

e20726 Background: At present, third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the standard first-line treatment for advanced EGFR-mutant non-small cell lung cancer (NSCLC). Nevertheless, the combination of first-/second-generation EGFR-TKIs and chemotherapy or anti-angiogenic agents remains commonly used in real-world practice in China. This study aimed to compare the real-world effectiveness of these two first-line strategies. Methods: In this retrospective study, data were collected from Shanghai Chest Hospital from January 2017 to December 2023. Previously-untreated patients with stage III/IV EGFR-mutant NSCLC were enrolled and classified into two groups: those receiving first-line first-/second-generation EGFR-TKI combination therapy, and those receiving third-generation EGFR-TKI monotherapy. Propensity-score matching (PSM) (1:2 ratio) was performed to balance baseline characteristics. The primary endpoint was progression-free survival (PFS). Overall survival (OS) was a secondary endpoint. Results: A total of 512 eligible patients were enrolled and the median follow-up was 40.4 months. After PSM, 364 patients were included. The median PFS was significantly longer in the third-generation TKI monotherapy group (n = 130, PFS: 20.5 months; 95% confidence interval [CI], 16.45-24.55) compared to the first-/second-generation TKI combination group (n = 234, median PFS: 16.0 months; 95% CI, 14.16-17.91; P &lt; 0.001). Subgroup analysis of PFS consistently favored the third-generation EGFR-TKI across almost all variables. No significant difference in OS was observed between the two groups (46.1 months, 95%CI 39.64-52.49 vs. 41.6 months, 95%CI 38.51-45.14; P = 0.721). Besides, 165 (70.5%) patients in the combination group received third-generation EGFR-TKIs in later lines, and this subgroup demonstrated significantly longer OS than those who did not (45.4 vs 33.5 months, P = 0.017). Conclusions: This real-world study demonstrates that first-line third-generation EGFR-TKI monotherapy is associated with a significantly improved PFS compared to first-/second-generation EGFR-TKI combination therapy in EGFR-mutant NSCLC. The absence of OS difference may be attributed to the high proportion of patients in the combination group who subsequently received third-generation TKIs as a later-line therapy. These findings support the superior efficacy of third-generation EGFR-TKIs as the recommended first-line treatment and also indicate that the first-/second-generation EGFR-TKI combination therapy is a viable alternative in real-world practice.

Impact of anemia on real-world outcomes in myelofibrosis: A propensity-matched analysis.

e18609 Background: Anemia is a frequent complication of myelofibrosis (MF) and is embedded in widely used prognostic systems, yet contemporary real-world estimates of its association with long-term survival and leukemic transformation remain limited. We evaluated the impact of baseline anemia (hemoglobin [Hb] &lt;10 g/dL) on overall survival (OS) and risk of transformation to acute myeloid leukemia (AML) in adults with MF. Methods: We performed a retrospective cohort study using the TriNetX Research Network, identifying adults (≥18 years) with myelofibrosis and stratifying them by anemia status at index (Hb &lt;10 g/dL). Patients with the outcome of interest prior to each analytic window were excluded. To minimize confounding, cohorts were 1:1 propensity score–matched using nearest-neighbor matching with a caliper of 0.1 pooled standard deviations of the logit of the propensity score, adjusting for demographic factors, comorbidities, iron supplementation, leukocyte count, and platelet count. Balance was assessed using standardized mean differences &lt;0.1. The primary outcome was all-cause mortality and the secondary outcome was transformation to AML, assessed at 1, 3, and 5 years. Risk estimates were calculated, and survival analyses were performed using Kaplan–Meier curves and Cox proportional hazards models, with statistical significance defined as a two-sided p&lt;0.05. Results: After matching, 18,504 patients with MF were identified, of which 51.6% were females and 48.3% were males. The mortality rate in patients with anemia was higher than in those without at years 1, 3, and 5: 21.4%, 33.2%, and 39%, respectively, versus 5.4%, 12%, and 16.9%, respectively. The prevalence of transformation to AML was also higher in patients with anemia at 3.7%, 4.9%, and 5.3% at years 1, 3, and 5, respectively, versus 0.1%, 0.3%, and 0.4% in patients without anemia at those same time points. The HR for mortality in MF patients with anemia when compared to those without anemia at years 1, 3, 5 was statistically significant at 4.57 (95% CI 4.14-5.05, log-rank p&lt;0.01), 3.51 (95% CI 3.28-3.76, log-rank p&lt;0.01), and 3.04 (95% CI 2.87-3.23, log-rank p&lt;0.01) respectively. The HR for transformation to AML in patients with MF with anemia versus those without anemia was statistically significant at years 1, 3 and 5, with HRs of 34.96 (95% CI 19.17-63.75, log-rank p&lt;0.01) 20.75 (95% CI 13.97-30.83, log-rank p&lt;0.01) and 17.07 (95% CI 12.11-24.07, log-rank p&lt;0.01), respectively. Conclusions: In this large, propensity-matched real-world EHR analysis, baseline Hb &lt;10 g/dL was associated with substantially worse OS and a markedly higher risk of AML transformation through 5 years. These findings support anemia as a pragmatic risk marker to inform risk-adapted monitoring, supportive care, and therapeutic decision-making in MF.

Prevalence and clinical significance of AR-V7 in extra-prostatic malignancies: A systematic review.

e15181 Background: Androgen receptor splice variant 7 ( AR-V7 ) is a constitutively active androgen receptor isoform lacking the ligand-binding domain. AR-V7 is a well-established mediator of resistance to androgen receptor (AR) targeting therapies in prostate cancer (PCa). Although AR-V7 has been increasingly reported in non-prostatic malignancies, its prevalence, biological significance, and clinical relevance outside the prostate remain poorly defined. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Major databases and oncology/pathology conference proceedings were searched until October 2025. Studies reporting AR-V7 expression in non-prostatic malignancies were included. Data on cancer type, AR-V7 detection methods, prevalence, treatment context, and clinical outcomes were extracted and synthesized narratively due to methodological heterogeneity. Results: Thirty-four studies encompassing 4855 clinical cases and 60 cancer cell lines were included. Overall, AR-V7 was detected in 948 cases (19.5%). Breast cancer accounted for the largest absolute number of AR-V7 –positive cases (815/948; 86.0%), although its within-cancer prevalence was modest (815/4,057; 20.1%) and highly sensitive to detection methodology. Higher proportional prevalence was observed in salivary duct carcinoma (55.2%), hepatocellular carcinoma (57.1%), and non–muscle-invasive bladder carcinoma (82.6%). AR-V7 was mostly detected in treatment-naïve cancers across several malignancies. Across breast cancer cell lines, AR-V7 expression was exclusive to AR-positive contexts and commonly co-existed with additional splice variants. Conclusions: AR-V7 is detectable across multiple non-prostatic malignancies, with marked heterogeneity by cancer type and detection method. Unlike prostate cancer, where AR-V7 typically emerges as a mechanism of acquired resistance after androgen-directed therapy, AR-V7 is present in a substantial subset of treatment-naïve extra-prostatic cancers, supporting its role as an intrinsic, tumor-specific molecular feature. Larger, prospective studies are warranted to define its prognostic and predictive utility to refine future AR-targeted strategies in precision oncology. Protocol registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251083307.