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Impact of remote therapeutic monitoring on time to discontinuation and acute care events among patients treated with immune checkpoint inhibitors.

11108 Background: Immune checkpoint inhibitors (ICI) are used to treat several solid tumors but can cause serious toxicities which may lead to early discontinuation of therapy. This study describes the effect of the Canopy electronic patient-reported outcomes (ePROs)-based remote therapeutic monitoring (RTM) platform on time to treatment discontinuation, acute care events, and steroid prescribing in patients receiving ICI therapy. Methods: We studied patients with metastatic cancer from four oncology clinics who started ICI treatment from Jan 1, 2024 to July 20, 2025. An RTM group was defined by submission of two ePRO reports in the first 45 days after first ICI treatment. The control group was never enrolled or did not submit ePRO reports within 45 days. Time to discontinuation (TTD) of ICI, acute care events, and steroid prescribing were assessed using propensity score weighting to account for potential differences in cohort characteristics; costs were taken as rate differences multiplied by average acute care event cost. TTD was assessed by Kaplan-Meier estimation, Cox proportional hazards modeling, and restricted mean survival time at 90 days (RMST). Descriptive statistics were taken about symptoms in the RTM group versus the control group. Results: The study included 363 patients using RTM and 1,199 in the control group. Lung cancer, melanoma, and kidney cancer were the most frequent diagnoses. In the RTM group time to treatment discontinuation was significantly greater and prescriptions for steroids were more frequent (Table 1). Additionally, RTM use was associated with about a 51% risk of hospitalization (95% CI: 0.29, 0.88, p: 0.015) and 82% risk of ER visits (95% CI: 0.49, 1.39, p: 0.458) compared to the control group. Estimated cost savings in hospitalization associated with RTM use were $11,733,933 per 1000 patients treated for one year. Symptoms were detected more frequently in the RTM group compared to the control group, including potentially ICI-related symptoms such as rash (18% vs 3.2%), diarrhea (28% vs 4.7%), and difficulty breathing (28% vs 4.8%). Conclusions: Active ePRO-based RTM with Canopy is associated with increased time to ICI discontinuation and decreased acute care events. Increased use of steroids in patients reporting symptoms suggesting ICI toxicity may explain the beneficial effect of RTM. Weighted analysis outcomes. Outcome RTM group Control group Risk or Hazard RatioRTM / Control (95% CI) Risk or RMST differenceRTM - Control (95% CI) Time to discontinuation Median: 7.5 mos(95% CI: 6.7, 8.8) Median: 4.1 mos(95% CI: 3.6, 4.6) 0.55(95% CI: 0.47 to 0.64, p < 0.001) 19 days (16, 22) Hospitalization 6.9% 14% 0.51 (0.29, 0.88, p: 0.015) -6.66 (-11.02, -2.13, p: 0.008) Emergency room visit 9.9% 12% 0.82 (0.49, 1.39, p: 0.458) -2.46(-8.05, 2.95, p: 0.366) Steroid use 53% 31% 1.69 (1.41, 2.02, p < 0.001) 21.67(13.90, 29.13, p < 0.001)

Factors associated with mood and anxiety disorders in cancer survivors: A systematic review and meta-analysis.

e24106 Background: Mood and anxiety disorders affect up to 38% of cancer survivors and are associated with poorer quality of life and survival. These disorders remain underdiagnosed and undertreated due to limited psychiatric resources and lack of systematic identification of high-risk patients, despite guidelines for routine screening and intervention. To inform risk-stratified mental health care in oncology, we conducted a systematic review and meta-analysis to identify risk factors for mood and anxiety disorders (new/recurrent diagnoses or clinically significant symptoms) in adult cancer survivors. Methods: We systematically reviewed cohort and case-control studies evaluating cancer-related (tumor characteristics and treatments), sociodemographic, lifestyle, and psychosocial risk factors for mood and anxiety disorders in adults with breast, lung, colorectal, prostate, stomach, liver, or pancreatic cancer. We searched PubMed, Web of Science, EMBASE, PsycINFO, and Cochrane (January 2000-November 2024). Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random-effects models with robust variance estimation for factors assessed in ≥ 5 studies. Factors assessed in 3-4 studies were summarized qualitatively. Results: Of 53 eligible studies, 50 were meta-analyzed. Across cancers, high tumor stage (vs. low, n=28, pooled RR [95% CI] = 1.55 [1.21-1.97]), more physical comorbidities (vs. fewer, n=36, 1.57 [1.34-1.84]), prior psychiatric history (yes vs. no, n=13, 4.85 [2.77-8.50]), female sex (vs. male, n=19, 1.52 [1.32-1.75]), underweight body mass index (vs. normal weight, n=6, 1.93 [1.55-2.44]), unmarried status (vs. married, n=25, 1.35 [1.14-1.58]), and current smoking (vs. never, n=12, 1.27 [1.12-1.46]) were consistently associated with higher risk of these disorders. We also found suggestive associations, though less consistent in sensitivity analyses, for high tumor grade (vs. low, n=7, 1.49 [1.02-2.16]), more extensive surgery (vs. limited, n=27, 1.16 [1.01-1.35]), low income (vs. high, n=13,1.52 [1.15-2.00]), low education (vs. high, n=29, 1.43 [1.15-1.82]), and low social support (vs. high, n=13, 2.63 [1.67-4.17]). In breast cancer-specific analyses, receipt of chemotherapy was associated with an increased risk of mood disorders (vs. no, n=9, 1.21 [1.04-1.40]). Systematic review also identified pain, fatigue, physical inactivity, and lack of insurance as additional, but understudied factors. Conclusions: This first meta-analysis identified several clinical and social factors consistently associated with increased risk of mood and anxiety disorders in adult cancer survivors. Findings inform risk-based psychiatric screening and early intervention strategies in resource-limited oncology settings. Additionally, they motivate future research to clarify causal pathways and test targeted preventive approaches.

Safety and preliminary efficacy of a novel armored mesothelin-targeted CAR-T therapy in advanced solid tumors.

2543 Background: UCMYM802 is an autologous mRNA-electroporated CAR-T cell therapy targeting mesothelin (MSLN), incorporating a lymphocyte-antigen-presenting cell costimulatory (LACO-Stim) molecule. This first-in-human study aimed to assess its safety, tolerability, preliminary efficacy, and pharmacokinetic/pharmacodynamic (PK/PD) profiles. Methods: This phase I study enrolled patients with metastatic or recurrent MSLN-positive solid tumors who failed standard therapies. Three dose levels were evaluated: 1×10 8 (n = 1), 5×10 8 (n = 1), and 1×10 9 CAR-T cells (n = 7). No lymphodepletion was required prior to infusion. Patients received up to 4 weekly infusions. Primary endpoints were safety and determination of the maximum tolerated dose (MTD). Secondary endpoints included objective response rate (ORR) by RECIST v1.1, disease control rate (DCR), and PK/PD parameters. Results: As of Nov. 2025, 9 patients were enrolled and treated (median age 67, range 52-67). Tumor types included pancreatic cancer (n = 3), peritoneal malignant mesothelioma (n = 1), adenocarcinoma of unknown primary, consistent with a gynecologic or peritoneal origin (n = 1), extrahepatic cholangiocarcinoma (n = 1), cholangiocarcinoma (n = 1), ovarian cancer (n = 1), and lung cancer (n = 1). All patients received at least one infusion. The 1×10 9 dose level was defined as the MTD, with one dose-limiting toxicity (DLT) observed (grade 4 cytokine release syndrome [CRS] with hypotension). Treatment-related adverse events (TRAEs) occurred in all patients, most commonly CRS (88.9%), fever (88.9%), decreased lymphocyte count (77.8%), anemia (77.8%), prolonged prothrombin time (66.7%), and hypoxia (55.6%). Grade ≥3 CRS occurred in 25% of patients. Among seven efficacy-evaluable patients, two patients achieved partial response (PR; one each in 5×10 8 and 1×10 9 cohorts), and two had stable disease (SD; one each in 1×10 8 and 1×10 9 cohorts). The ORR was 28.6% (2/7) and DCR was 57.1% (4/7). Notable responses included a PR in gynecologic or peritoneal origin adenocarcinoma and a PR at 6 months (converted to SD at 7.5 months) in extrahepatic cholangiocarcinoma. PK analysis showed peak CAR-T expansion (by copy number) at 1-hour post-infusion, with the highest and most sustained exposure after the first infusion. PD analysis indicated IFN-γ elevation correlating with CAR-T peak expansion. CAR-T exposure and activation marker expression showed a dose-dependent trend. Conclusions: UCMYM802 demonstrated a manageable safety profile consistent with expected CAR-T-related toxicities, primarily CRS. Preliminary anti-tumor activity was observed in heavily pretreated patients with MSLN-positive advanced solid tumors, with encouraging signals in gynecologic or peritoneal origin adenocarcinoma and biliary tract cancers. The recommended dose for expansion is 1×10^9 CAR-T cells. These results support continued investigation of UCMYM802. Clinical trial information: NCT06256055 .

Lipid-lowering therapy use among cancer survivors undergoing lung cancer screening: A cross-sectional analysis.

12029 Background: Cardiovascular disease (CVD) causes 56% of non-cancer deaths among cancer survivors, yet lipid-lowering therapy (LLT) remains underutilized. Moreover, lung cancer screening (LCS) populations exhibit a dual high-risk profile, characterized by heavy smoking exposure and a history of cancer. We sought to examine the utilization of LLT among cancer survivors undergoing LCS and to identify disparities based on demographics, clinical factors, and social determinants of health. Methods: We conducted a cross-sectional study of 7,778 cancer survivors aged 50–80 years who underwent LCS through Barnes-Jewish Healthcare's LCS program between 2015 and 2023. The primary outcome measured was LLT use, specifically statins or statin substitutes, as documented in electronic health records. We assessed for associations with demographics (age, sex, race), clinical factors (prior ASCVD, cancer type), healthcare access (insurance status, rurality via Rural-Urban Commuting Area codes), and the Area Deprivation Index (ADI). The data were analyzed using multivariable logistic regression, adjusted for demographics, insurance status, smoking, indication, and provider, with results stratified by race and sex. Results: Overall, 65.8% of cancer survivors undergoing LCS used LLT. Compared with lung cancer, prostate (AOR = 1.35; 95% CI 1.08–1.71), hematologic (AOR = 1.35; 95% CI 1.03–1.76), and other solid cancers (AOR = 1.23; 95% CI 1.07–1.42) were associated with higher LLT use. When stratified by race, among White patients, male sex was associated with higher LLT use (AOR = 1.13; p = 0.036) and rural residence was associated with lower LLT use (AOR = 0.81; p = 0.005); these were not significant factors in Black patients. Prior ASCVD was the strongest associated factor (AOR = 2.54, p < 0.001), followed by age ≥65 years (AOR = 1.41, p < 0.001). Rural residence was associated with 29% lower odds of LLT use (AOR = 0.71, p < 0.001) even after adjusting for all other factors. Insurance status, and neighborhood deprivation were not associated with LLT use. Conclusions: LLT remains underused among cancer survivors at high cardiovascular risk, even during routine LCS. Rural patients were less likely to receive therapy, underscoring persistent geographic gaps in preventive care. The strong association of prior ASCVD with LLT use suggests that therapy is still primarily utilized reactively rather than preventively. Improving follow-up and care coordination during screening could help close prevention gaps and reduce heart disease deaths in cancer survivors.

First-line maintenance therapy patterns in <i>BRCA</i> wild-type and HRD-negative advanced epithelial ovarian cancer: A European real-world study.

e17552 Background: Maintenance therapy is central to the management of advanced epithelial ovarian cancer (AEOC), yet real-world patterns in biomarker-negative populations (i.e. BRCA wild-type, HRD-negative or biomarker-unknown) remain poorly described. Cross-country differences may reflect variability in clinical practice, regulatory approvals and reimbursement. Methods: Oncologists from the EU5 (UK, France, Germany, Italy and Spain) contributed anonymised patient charts between November 2024 and March 2025 for a real-world study of first-line (1L) maintenance in BRCA wild-type, HRD-negative or biomarker-unknown AEOC. Eligible patients had FIGO stage III–IV disease. Maintenance therapies received were recorded. Inter-country differences in treatment allocation were assessed using a chi-square test. Pearson residuals and p-values were calculated to identify statistically significant variation in prescription patterns. Results: The study included 977 patients. Reported maintenance treatments were surveillance (n = 110; 11.3%), bevacizumab (bev; n = 380; 38.9%), niraparib (nira; n = 385; 39.4%), rucaparib (ruca; n = 31; 3.2%), and other therapies (n = 71; 7.3%). Maintenance choice varied significantly across countries (χ² = 147.8, df = 16, p &lt; 0.0001). Surveillance was chosen more frequently in the UK (n = 63; 18.6%, p &lt; 0.0001) and less frequently in Germany (n = 5; 2.8%, p = 0.0007). Bev use was significantly higher in France (n = 182; 57.6%, p &lt; 0.0001) and lower in the UK (n = 74; 21.9%, p &lt; 0.0001). Nira was chosen more often in the UK (n = 171; 50.6%, p = 0.0011) and less often in France (n = 92; 29.1%, p = 0.0036). Ruca was used infrequently across all countries, with no statistically significant inter-country differences observed (p = 0.41). Conclusions: Real-world maintenance choices for biomarker-negative AEOC vary considerably across the EU5. These differences likely reflect heterogeneity in clinical practice, drug availability and reimbursement frameworks. Further research aiming to explore these patterns may help support more aligned, evidence-informed treatment decisions across healthcare systems.

Uterine serous and clear cell carcinomas: Hormonal profile and expression of steroid hormone receptors in mitochondria.

e17624 Background: Uterine serous carcinoma (USC) and clear cell carcinoma (CCC) are rare but aggressive histological subtypes of endometrial cancer associated with a poor prognosis. Beyond their classical role in energy metabolism, mitochondria are involved in cell signaling. Steroid hormone receptors are localized within mitochondria, allowing estrogens, progesterone, and androgens to directly influence mitochondrial function, thereby regulating apoptosis and energy metabolism. The aim of this study was a comparative assessment of steroid hormone levels and their receptor expression in mitochondria isolated from USC and CCC tissues versus mitochondria from intact endometrium. Methods: Mitochondria were isolated from tumor tissues of 41 patients with rare forms of endometrial cancer: USC (n=21) and CCC (n=20). All patients presented with stage III–IV, high-grade (G3) disease; the mean age was 59.6±6.7 years. Mitochondria from histologically normal (intact) endometrium (n=20) obtained from women undergoing surgery for uterine fibroids (mean age 57.8±8.2 years) served as controls. Concentrations of estrone (E1), estradiol (E2), estriol (E3), testosterone (T), progesterone (P4), and receptors (ERα, ERβ, AR, PR) were determined in the purified mitochondrial fraction using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using parametric and nonparametric tests with adjustments for multiple comparisons. Results: In USC and CCC mitochondria, a statistically significant (p &lt; 0.05) increase was observed compared to the control group for: E2 (1.3- to 2-fold), E3 (1.8- to 2.2-fold), P4 and T (1.5-fold on average), ERβ (more than 2-fold), and PR (3.4- to 5.2-fold). However, ERα and AR levels were significantly increased only in USC (1.8-fold, p &lt; 0.05 and 2.2-fold, p &lt; 0.05, respectively), whereas no significant differences were found in CCC mitochondria. Conclusions: The findings demonstrate significant alterations in the mitochondrial hormonal and receptor profiles in serous and clear cell endometrial carcinomas. Overexpression of ERβ and PR, alongside the accumulation of steroid hormones, indicates the activation of mitochondrial hormonal signaling pathways. The observed differences suggest distinct mechanisms of hormonal regulation: estrogen- and androgen-dependent signaling predominates in USC, while progesterone-dependent signaling predominates in CCC. These features may determine differences in the biological behavior of these tumors and their response to therapy.

Artificial intelligence (AI)–augmented analysis of quantitative circulating tumor DNA (ctDNA) burden and longitudinal kinetics to identify prognostic risk stratification in metastatic clear cell renal cell carcinoma (mccRCC).

4522 Background: The relevance of ctDNA burden and longitudinal kinetics in RCC remains poorly defined. We applied AI–based analysis of quantitative ctDNA trajectories to identify prognostically informative patterns beyond baseline detection. Methods: We analyzed patients with mccRCC undergoing longitudinal tumor-informed ctDNA testing (Signatera) during first-line immune checkpoint inhibitor–based therapy. Quantitative ctDNA burden in mean tumor molecules per milliliter (MTM/mL) was measured serially and aligned to treatment initiation, with radiographic response classified as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). ctDNA trajectory similarity was independently assessed using dynamic time warping (DTW), trajectory-based K-means clustering, and a neural network sequence autoencoder (TensorFlow) with clustering to learn latent representations of ctDNA kinetics. Cross-method concordance was used to define robust ctDNA kinetic phenotypes. Results: Survival and response analyses included 93 patients with mccRCC with longitudinal ctDNA profiling. Baseline ctDNA detectability was not significantly associated with OS. Conversion from ctDNA-positive to ctDNA-negative status during therapy was associated with improved OS (p&lt;0.05). Patients with radiographic disease control (CR/PR/SD) had significantly lower peak ctDNA levels than those with progressive disease (median 0.18 vs 8.86 MTM/mL; p=0.007). Increasing peak ctDNA burden was strongly associated with inferior OS (HR 2.21, 95% CI 1.63–3.01; p&lt;0.001). A machine learning–based spline-regularized Cox survival model identified a high-risk ctDNA threshold &gt;20 MTM/mL associated with worse OS (p=0.034). Trajectory-based K-means identified an optimal solution at k=4 clusters, independently supported by DTW and autoencoder-based analyses. Four ctDNA kinetic phenotypes repeatedly emerged: early ctDNA clearance, early ctDNA rise, delayed ctDNA clearance, and persistently low-level ctDNA. Autoencoder-derived phenotypes demonstrated strong internal robustness (Adjusted Rand Index, ARI ≈ 0.80) and high concordance with DTW-based clustering. Phenotypes were associated with distinct radiographic response and survival patterns, with early ctDNA rise conferring the poorest OS (p=0.022). Conclusions: AI-driven modeling of quantitative ctDNA burden and longitudinal kinetics identifies biologically interpretable and reproducible prognostic phenotypes in RCC, capturing higher-order temporal features of ctDNA dynamics and providing prognostic stratification beyond baseline detectability and burden alone, thereby informing clinical decision-making regarding earlier therapy switching.

Role of gallium-68-labeled FAPI-PET imaging in oncology: Results of a study in 310 patients.

e15076 Background: Current oncological PET imaging approaches rely on metabolic targets, primarily 18 F-FDG, and this leads to diagnostic limitations in tumors with low proliferation, a predominant fibrotic stroma, or post-treatment changes. Fibroblast activation protein (FAP) is a widely expressed target in the tumor stroma, such as cancer-associated fibroblasts (CAFs), in numerous solid tumors. Gallium-68-labeled FAPI PET imaging is emerging as a novel, tumor-agnostic imaging paradigm that evaluates tumor biology at the stromal level. Methods: In our study, we performed 68 Ga-FAPI PET/CT and 18 F-FDG PET/CT imaging on 310 patients with different solid tumor diagnoses. The study population included lung, breast, gastrointestinal system, gynecological, genitourinary, hepatobiliary, thyroid, and rare solid tumors. Although multiple FAPI-PET examinations were performed in the same patient, the analysis was performed on a patient-by-patient basis. The images were evaluated by comparing FAPI uptake in primary and metastatic lesions with FDG. Results: A total of 310 patients underwent 68 Ga-FAPI PET/CT and 18 F-FDG PET imaging for comparison. Significant FAPI uptake was observed in the primary tumor and/or metastatic lesions in all cases, and in many cases, significant SUV values were present on FAPI-PET, which was more sensitive than FDG. Patient distribution was as follows: lung cancer (n = 33), breast cancer (n = 47), colorectal cancer (n = 47), gastric cancer (n = 29), pancreatic cancer (n = 17), hepatobiliary tumors (n = 8), prostate cancer (n = 8), gynecological tumors (n = 4), and thyroid cancer (n = 1). In addition, 116 patients had various rare solid tumor diagnoses. FAPI PET imaging demonstrated superior lesion detection performance by providing high tumor-background contrast with low physiological background activity in all tumor groups. Conclusions: This large patient series demonstrated that 68 Ga-FAPI PET imaging exhibits higher sensitivity than FDG-PET in solid tumors across the board. FAPI PET, which provides stromal-targeted imaging independent of tumor type, is a method that complements conventional metabolic imaging approaches and surpasses them in many clinical scenarios. Our findings strongly support the integration of 68 Ga-FAPI PET into clinical oncology imaging algorithms and guidelines. Distribution of tumor types in patients undergoing 68 Ga-FAPI PET/CT imaging. Tumor Type n Breast cancer 47 Colorectal cancer 47 Lung cancer 33 Gastric cancer 29 Pancreatic cancer 17 Hepatobiliary tumors 8 Prostate cancer 8 Gynecologic tumors 4 Thyroid cancer 1 Other solid tumors 116 Total 310 All patients underwent both 18 F-FDG PET/CT and 68 Ga-FAPI PET/CT imaging. Tumor types are reported on a per-patient basis. Visually significant tracer uptake was observed in all cases on 68 Ga-FAPI PET/CT.

Impact of diabetes mellitus on inpatient outcomes among hospitalized patients with multiple myeloma: A National Inpatient Sample analysis (2018–2020).

e19540 Background: Diabetes mellitus (DM) is common in patients with multiple myeloma (MM). While DM is often perceived as a significant risk factor for complications, its independent impact after adjusting for key comorbidities particularly renal and cardiovascular disease is not well defined. We evaluated whether DM status independently influences in-hospital mortality and resource utilization or if these outcomes are primarily driven by other comorbid conditions. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (2018–2020). Adult hospitalizations with multiple myeloma (MM) were stratified by diabetes mellitus (DM) status. Primary outcomes were in-hospital all-cause mortality, length of stay (LOS), and inflation adjusted total hospital charges (THC). Secondary outcomes included acute kidney injury (AKI), venous thromboembolism (VTE), sepsis, respiratory failure, and requirement for mechanical ventilation. Survey-weighted multivariable regression models adjusted for demographics, comorbidities, hospital characteristics, and illness severity were used to assess associations between DM and inpatient outcomes. Results: Among 62,870 MM hospitalizations, 13,980 (22.2%) had comorbid DM. Patients with DM were older (median 68 vs 65 years, p&lt;0.001), more frequently male (58% vs 55%, p=0.003) and had a higher baseline prevalence of hypertension (HTN) (57% vs 84%, p&lt;0.001) and chronic kidney disease (CKD) (40% vs 26%, p&lt;0.001). DM was not independently associated with the primary outcomes of mortality (aOR 0.87, p=0.2), length of stay (p=0.7), or inflation adjusted THC (p=0.4). Regarding secondary outcomes, DM status was not independently associated with AKI (aOR 0.95, p=0.4), sepsis (aOR 1.06, p=0.6), respiratory failure (aOR 0.93, p=0.4), or mechanical ventilation (aOR 1.00, p&gt;0.9). A borderline lower risk of VTE was observed (aOR 0.79, 95% CI 0.62–1.00, p=0.053). Notably, the risk for adverse outcomes was strongly driven by other comorbid factors such as pre-existing HTN, CKD, hyperlipidemia, coronary artery disease (CAD), obesity and heart failure whereas DM was only a borderline independent risk factor for VTE after multivariable adjustment. Conclusions: In hospitalized patients with multiple myeloma, diabetes mellitus does not independently worsen short-term mortality, clinical complications, or healthcare utilization. The elevated risks observed in this population are comorbidity-dependent rather than DM-specific. These findings suggest that inpatient management should focus on the optimization of concurrent conditions specifically renal impairment, cardiovascular disease and obesity as these are the true drivers of adverse outcomes in MM hospitalizations.

Tinengotinib (TT-00420) in advanced/metastatic FGFR2-altered cholangiocarcinoma following prior chemotherapy and FGFR inhibitor treatment: Results from a phase II study (FIRST-08).

4133 Background: Subsequent treatment options for advanced cholangiocarcinoma (CCA) after failure of chemotherapy and FGFR inhibitors (FGFRi) are limited. Tinengotinib (TT-00420), a novel FGFRi, potently inhibited FGFR2 fusion/rearrangement and acquired resistant/FGFR2 kinase domain mutations. The FIRST-08 study is an open-label, multicenter Phase II study in Chinese patients (pts) with advanced/metastatic CCA (NCT06057571). Methods: Eligible pts with advanced/metastatic CCA harboring FGFR2 fusion or arrangement, who had failed prior chemotherapy and one FGFRi, received tinengotinib 10 mg orally once daily in 21-day cycles. The primary endpoint was objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included progression free survival (PFS), disease control rate (DCR), duration of response (DoR), overall survival (OS), safety, PK and quality of life (QOL) per EORTC QLQ-C30. Results: As of June 27, 2025, 50 pts were enrolled (median age 56.5 years; 52.0% male; ECOG of 1: 44.0%). Median follow-up was 8.5 months. Forty percent had ≥ 3 prior systemic regimens, 66.0% had prior immunotherapy, and 42.0% had received other targeted therapies beyond FGFRi. The ORR by BICR was 28.0% (95%CI, 17.5~41.7) with 14 confirmed partial responses, and median DoR was 7.9 (5.6~ -) months. The disease control rate (DCR) was 82.0%. The median PFS was 5.7 (4.3~8.3) months. The median OS had not reached, with the 18 months survival rate 66.9% (47.3~80.6). Common Gr3/4 TRAEs (≥15%) included hypertension (42.0%), palmar-plantar erythrodysesthesia syndrome (16.0%), No Gr 5 TRAE was observed. 41 out of 50 pts had biomarker ctDNA samples collected at baseline, 82.9% pts had FGFR2 fusion and 48.8% had FGFR2 mutation (SNV). 28 pts had biomarker ctDNA samples collected at both baseline and C3D1. A significant decrease in maximum variant allele frequencies (MaxVAF) from baseline to C3D1 by a median relative VAF reduction of 83.7% (p&lt;0.0001), indicating strong molecular response to tinengotinib. Conclusions: Tinengotinib demonstrated durable clinical anti-tumor activity and a manageable safety profile in heavily pretreated CCA pts with FGFR2 fusion/rearrangement following prior chemotherapy and FGFRi therapy. Clinical trial information: NCT06057571 . Efficacy outcomes by BICR and investigator. BICR Investigator ORR, % (95%CI) 28.0 (17.5~41.7) 20.0 (11.2~33.0) DCR, % (95%CI) 82.0 (69.2~90.2) 78.0 (64.8~87.3) mPFS, months (95%CI) 5.7 (4.3~8.3) 6.9 (4.3~8.5) mDoR, months (95%CI) 7.9 (5.6~ -) 6.6 (2.4~ -)

Valuing conservation and natural wealth: The blue economy of manta ray watching in the Maldives

Amid declining manta ray populations globally, the well-established and growing manta ray tourism industries generate substantial economic benefits and aid protective legislation for these threatened elasmobranchs. As flagship species, manta rays are a drawcard for marine wildlife tourism and a gateway for engaging the public and communities in conservation. Healthy marine ecosystems are the key drivers of employment and economic sustainability for island nations such as the Maldives. However, there are many stakeholders competing for these shared resources, which can result in environmental degradation. Economic valuations are a powerful tool for justifying the conservation efforts of threatened species and natural areas, especially in light of competing stakeholders. Using tour operator surveys ( n  = 106) and data mining, this study provides an updated assessment of manta ray watching tourism in the Maldives and represents the first national valuation of its direct economic and socio-economic benefits. In 2021, manta ray tourism in the Maldives generated an estimated US$227.3 million, including US$39 million on manta ray focused diving and snorkelling excursions, and US$188.3 million in related tourist expenditure, representing 2.6% of the national Gross Domestic Product. This industry appears to have grown around 380% since 2008 (US$8.1 million) and manta ray watching is now offered by 80% of tourism operators nation-wide. Our findings revealed that manta rays hold intrinsic value and cultural significance within local communities. Acknowledging this, the flow-on benefits to the community extend beyond this industry, reaching local businesses, employed staff, and the government with the direct economic benefits of the manta ray tourism industry are estimated at over US$311 million per year. Such value highlights the significance of manta rays for the Maldives and the need for effective management centred on manta ray conservation to safeguard future prosperity and mitigate the potential impact of tourism on manta ray populations.

Smart drug delivery systems for potential targeted cancer therapy: Exploiting increased glutathione levels in tumor microenvironments

Tryptamine Terminated Low‐Dimensional Interfaces Enabled High Performance Perovskite/Silicon Tandem Solar Cells

ABSTRACT The construction of a high‐quality interface with excellent surface passivation and carrier transport is critical to the device performance of solar cells. Low‐dimensional perovskite structures are widely explored for surface passivation due to their effective suppression of interfacial defects and enhanced environmental stability. While terminal molecules for constructing low‐dimensional structures provide excellent passivation, they can introduce potential barriers for charge transport if the energy levels are not well‐aligned. Herein, a tryptamine molecule is explored as the terminal molecule for the construction of a low‐dimensional structure for passivating the buried interface of perovskite solar cells. Based on the inclusion of nitrogen atoms in the aromatic heterocyclic structure, the terminal molecule shows an uplifted HOMO level that aligns well with the perovskite skeleton, giving rise to enhanced orbit coupling. Therefore, this low‐dimensional structure enables excellent surface passivation and interfacial carrier transport simultaneously, generating an outstanding open‐circuit voltage ( V OC ) up to 1.266 V and an efficiency of 23.53% for single‐junction wide‐bandgap (1.68 eV) perovskite solar cells. This improvement enables the fabrication of the perovskite/silicon tandem solar cell with an efficiency of 33.22% (32.88% assessed by a third party) and a V OC of 1.987 V. Moreover, the fast carrier transport at the interface suppressed the halide phase segregation, bringing much enhanced operation stability.

A directional nanoantenna design based on a hybrid plasmonic waveguide: theoretical analysis for biosensing applications

Lipid transfer proteins and PI4KIIα initiate nuclear p53-phosphoinositide signaling

Influence of onboard, tethered IL-12 on potency of the Tmod NOT gate and selectivity.

2562 Background: To realize the full therapeutic potential of engineered immune cells in solid tumors, high potency must be coupled with absolute selectivity. While synthetic NOT logic gates, such as the LIR-1 NOT gate (Tmod) system, effectively address non-specific cytotoxicity, overcoming the suppressive tumor microenvironment (TME) requires auxiliary stimulation. This study focused on Interleukin-12 (IL-12)—a potent pro-inflammatory cytokine—as an “armoring” strategy to bridge this gap. Methods: We designed an antigen-inducible, membrane-tethered IL-12 system to boost antigen-specific Tmod activity. The performance of this inducible IL-12 construct was evaluated across various long-term in vitro and in vivo assays to measure Tmod T cell exhaustion (specifically the upregulation of PD-1 and downregulation of CD62L) and its ability to mitigate the immunosuppressive effects of TGFβ, a primary barrier in the solid tumor microenvironment. We further assessed the reversibility of IL-12 expression upon antigen clearance and monitored for IL-12 shedding both in vitro and in vivo. Results: The inducible IL-12 construct boosted antigen-specific Tmod activity, prevented T cell exhaustion, and effectively mitigated the immunosuppressive effects of TGFβ that typically hamper CAR-T persistence. Crucially, this potency boost did not “override” the LIR-1 blocker; the IL-12-enhanced cells remained selective, sparing normal cells. Furthermore, data showed that the expression of membrane-tethered IL-12 is reversible once the antigen is cleared. Minimal IL-12 shedding was observed, suggesting the pro-inflammatory signal remained localized to the immunological synapse. Conclusions: The antigen-inducible membrane-tethered IL-12 system enhances Tmod potency while maintaining a high degree of selectivity and an acceptable safety profile for clinical translation. An Investigational New Drug (IND) application for MSLN-targeted Tmod boosted by antigen-inducible membrane-tethered IL-12 has been approved by the FDA, and a Phase 1 clinical trial is currently ongoing.

Evaluating the organizational benefits of remote symptom monitoring during injectable outpatient cancer treatment: The final analysis of the randomized OPTIMACURE trial.

1637 Background: Remote monitoring (RM) to assess whether patients are apt for cancer treatment is already used during standard of care (SOC) in several French centers. Optima RM includes structured phone calls by a nurse, 2-3 days before the planned administration, with the transfer of biological results 48 h before the administration, with a physician’s validation the day before administration. Cureety RM, in addition to preparing visit, also monitors symptoms between cures. We aimed to evaluate the organizational benefit of Cureety RM compared to Optima-like RM in patients initiating outpatient injectable cancer treatments. Methods: OPTIMACURE was designed as a multicentric, randomized, open-label trial to compare Cureety RM versus Optima-like RM. Patients aged ³18 years, starting an injectable cancer treatment, and capable of using a RM tool were eligible. Patients with dysphonia/difficulties with oral communication were not eligible. Enrolled patients were randomly allocated (2:1) to either Cureety RM or to SOC (with Optima-like RM). Randomization was stratified by type of cancer treatment, ECOG PS, frequency of treatment, and center. Only centers using Optima-like RM participated in the trial. The primary objective was to assess the effectiveness of adding Cureety RM to usual care, in terms of the number of outgoing calls, overall and by reason (preparing visits or for toxicity), within the first 2 months. Secondary outcomes included safety, toxicity-free survival (TFS), and hospitalizations. Results: Between April and August 2024, 192 patients were allocated: 127 (66%) to Cureety RM and 65 (34%) to SOC (with Optima-like RM). The trial population was mainly female (73%) and with an ECOG PS 0-1 (96%). Most were being treated with chemotherapy (98%) and less frequently than every 2 weeks (61%). The demographic and disease characteristics were similar in the groups. The mean number of outgoing calls were fewer with Cureety RM, 2.53 (SD: 2.21) versus 3.77 (SD: 2.45). The difference of least-squares means was significantly different in the groups: -1.25 (95% CI: -1.91 to -0.59), p&lt;0.0001. The number of outgoing calls for preparing visit were significantly fewer with Cureety RM, 0.43 (SD: 0.82) versus 3.09 (SD: 2.18), p&lt;0.001. While there were significantly more outgoing calls for toxicity with Cureety RM, 1.68 (SD: 1.89) versus 0.20 (SD: 0.71), p&lt;0.001. No adverse events (AEs) related to RM were reported. The median TFS was significantly shorter with Cureety RM, 10 days versus not reached: driven by early detection of grade ≤4 AEs. The number of hospitalizations was similar in the groups. Conclusions: Implementing Cureety RM during injectable cancer treatment had an organizational benefit by reducing the number of outgoing calls. More precisely, reducing the outcalls for preparing visit while increasing those for AEs. Clinical trial information: NCT06371911 .

Physician ownership and investment interests in oncology: A national analysis of open payments data (2018-2024).

e23024 Background: Financial relationships between physicians and industry raise concerns about conflicts of interest. The Physician Payments Sunshine Act requires pharmaceutical and medical device manufacturers to report these relationships to the Centers for Medicare &amp; Medicaid Services (CMS) Open Payments program. Research into ownership, investment interests and oncology-specific analyses is limited despite long-term financial alignment and rapid therapeutic innovation. Methods: We conducted a retrospective observational analysis of physician ownership and investment interests using CMS Open Payments database from 2018–2024 in oncology-related specialties. General/research payments were excluded. Ownership was characterized by CMS-reported value of interest and amount invested. Differences across specialties and regions were assessed using Kruskal–Wallis tests with Dunn post-hoc comparisons, and temporal trends were evaluated using linear regression. Results: A total of 767 ownership/investment interests involving 127 physicians were reported by 43 drug and device manufacturers and GPOs. Hematologist-oncologists accounted for 60% of reports. The median ownership asset value was $5,000 (range $0–$2,106,176). 26% (n=200) of entries reported an investment in an applicable manufacturer/GPO in a year, with a median annual investment of $9,000 (range $15 to $946,498). Aggregate ownership asset value peaked in 2022 ($4.8 million). Significant variation was observed by region of physician and manufacturer/GPO (p &lt; 0.001), with pediatric hematology-oncology demonstrating the highest median ownership value. One GPO, Cornerstone Specialty Network, accounted for 80% (n=611) of all ownership and investment reports. Conclusions: Physician ownership or investment interests in manufacturers/GPOs among physicians in oncology fields are rare, involving ~0.5% of physicians, with variability by specialty and geography. These findings highlight the importance of continued scrutiny of equity-based financial relationships in oncology. Descriptive statistics of the median value of ownership assets and investment amounts by specialty. Number of reports (%) Median value of ownership assets (IQR) Number of entries that report investments (%) Median amount invested on yearly basis (IQR) Hematology &amp; Oncology 466 (61%) $5,000 ($3,479) 82 (18%) $9,000 ($5,122) Medical Oncology 175 (23%) $6,600 ($5,815) 49 (28%) $9,000 ($14,350) Radiation Oncology 99 (13%) $6,889 ($49,391) 57 (58%) $25,000 ($46,100) Gynecologic Oncology 11 (1%) $90,000 ($118,929) 4 (36%) $6,000 ($84,500) Surgical Oncology 11 (1%) $58,830 ($93,123) 5 (45%) $38,540 ($31,880) Pediatric Hematology-Oncology 5 (1%) $249,965 ($104,816) 3 (60%) $100,000 ($58,532)

Phase IIb randomized trial of FOLFIRINOX plus ibrilatazar (ABTL0812) versus placebo as first-line treatment in metastatic pancreatic cancer: An analysis from the PanC-ASAP study.

4218 Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) has poor prognosis and limited first-line treatment options. Ibrilatazar (ABTL0812) is a first-in-class oral agent that induces cytotoxic autophagy selectively in cancer cells. Favorable safety and tolerability of the combination with FOLFIRINOX were established in a Phase I study. D.S. and T.M. are equal contributors. Methods: PanC-ASAP is a Phase IIb double-blind, randomized, placebo-controlled (1:1) study evaluating the efficacy and safety of ibrilatazar (1300 mg TID) plus FOLFIRINOX versus placebo plus FOLFIRINOX as first-line therapy in mPDAC, conducted across 23 sites in the US, Spain, France, and Israel. Eligible patients had histologically confirmed mPDAC, ECOG PS 0–1, and no prior systemic treatment for metastatic disease. Treatment continued until disease progression or intolerable toxicity. Primary endpoint was progression-free survival (PFS), defined as time from randomization to radiographic disease progression or death, assessed by blinded independent central review in the intention-to-treat (ITT) population. Overall survival (OS) was a key secondary endpoint. Safety was assessed in all treated patients. Pre-specified stratification analysis revealed an imbalance in ECOG between arms (ECOG 0/1: 40%/60% ibrilatazar vs 54%/46% placebo), prompting an exploratory efficacy analysis by ECOG PS subgroup. Time-to-event endpoints were analyzed using Kaplan–Meier methods and log-rank tests. Results: In the ITT population (n = 140), median PFS for ibrilatazar vs placebo was 9.4 vs 7.9 mths (HR 0.95; 90% CI, 0.69-1.33; p = 0.814). An exploratory analysis by ECOG showed that, among patients with ECOG 0 (n = 66; ibrilatazar, n = 28; placebo, n = 38), median PFS of 11.1 vs 6.5 mths (HR 0.60; 95% CI, 0.34–1.08; p = 0.089), and median OS of 19.3 vs 12.0 mths (HR 0.57; 95% CI, 0.31–1.05; p = 0.072). Consistent trends favoring ibrilatazar were observed across efficacy endpoints, including objective response rate and duration of treatment. Safety profile of ibrilatazar plus FOLFIRINOX was consistent with the known FOLFIRINOX toxicities. The most common grade ≥3 treatment-emergent adverse events in the ibrilatazar vs placebo were neutropenia (21% vs 22%), diarrhea (21% vs 16%), and neurotoxicity (0% vs 14%). Conclusions: Although primary PFS endpoint was not met in the ITT population, exploratory analysis showed clinically meaningful and consistent efficacy improvements among ECOG 0 patients treated with ibrilatazar plus FOLFIRINOX, with 60% and 70% increases in median OS and median PFS respectively. These findings support further investigation in selected mPDAC populations and suggest ECOG may modify treatment benefit. Clinical trial information: NCT04431258 .

Tumor-of-origin prediction using methylation signals from plasma cell-free DNA (cfDNA): Real-world experience in Asia and the Middle East (AME).

3051 Background: Accurate identification of tumor tissue of origin (TOO) is essential for guiding treatment decisions in advanced cancers; however, tissue biopsies may be limited by accessibility, sample adequacy, or diagnostic delays. Plasma cfDNA-based methylation profiling provides a non-invasive approach for TOO determination and has demonstrated high agreement with clinicopathologic diagnoses in prior studies. However, real-world data from AME remains limited. We evaluated the real-world performance of a methylation-based TOO classifier using plasma cfDNA in this population. Methods: We retrospectively analyzed plasma cfDNA samples from patients with advanced solid tumors tested across AME using the Guardant360 Liquid assay through December 2025. The assay interrogates epigenomic signals from &gt;19,000 methylated regions. The TOO classifier assigns a ranked cancer signal of origin (CSO) based on tumor-specific methylation patterns, reporting a primary CSO prediction and, when confidence is intermediate, a secondary CSO prediction. CSO confidence is quantified algorithmically based on methylation signal strength and classification certainty. Only samples with medium (50–80%) or high (&gt;80%) confidence predictions were included. All tests were ordered as part of routine clinical care, and available clinicopathologic diagnoses (CPD) served as the reference standard. Results: Among 1,782 cfDNA-profiled samples, 1,230 (69%) yielded a CSO prediction with medium or high confidence. The primary CSO prediction matched CPD in 85% of cases overall, increasing to 91% when secondary CSO predictions were included. Tumor-type–specific accuracy varied, with the highest performance observed for colorectal, breast, and prostate cancers (94% each). Agreement with CPD was lower for gastroesophageal (72%) and kidney cancers (68%). Among 114 cancer of unknown primary (CUP) cases, a suspected clinical diagnosis was available for 48. Medium- or high-confidence CSO predictions were generated in 42 (87%). CSO predictions aligned with subsequent clinicopathologic consensus or confirmatory biopsy in 35 (83%), spanning 13 tumor types, most commonly lung cancer (24%). Therapy response evaluation was available for 12 patients, with partial response in 9 (75%) and stable disease in 3 (25%). Conclusions: In this real-world AME cohort, the TOO classifier identified probable tumor tissue of origin in most advanced cancer patients. CSO predictions showed high agreement with CPD across multiple tumor types. This approach demonstrated potential value in resolving CUP cases, with the predicted origin confirmed in 83% of evaluable patients. These findings support the clinical feasibility of methylation-based tumor-of-origin testing in AME and warrant further studies to evaluate its impact on clinical decision-making.