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3 kV fully vertical <i>β</i>-Ga2O3 junction termination extension Schottky barrier diode with sputtered p-GaN

In this work, we present the fabrication of a fully vertical β-Ga2O3 Schottky barrier diode with junction termination extension (JTE-SBD) utilizing a p-GaN layer produced by sputtering, offering a solution to the absence of p-Ga2O3 materials. The p-GaN/n-Ga2O3 JTE-SBD demonstrates a turn-on voltage (Von) of 0.8 V, a specific on-resistance (Ron,sp) of 6.15 mΩ·cm2, an ideality factor (n) of 1.24, a breakdown voltage of 3 kV, and a Baliga's Figure of Merit of 1.46 GW/cm2. The current–voltage–temperature (I–V–T) testing has confirmed a transition in the dominant leakage mechanisms from the Poole–Frenkel mechanism to variable-range hopping.

Research on intelligent routing with VAE-GAN in the internet of body

The "Internet of Body" is an emerging technology that is centered on the human body and connected to the Internet. It can monitor a variety of human data (such as heart rate, blood oxygen content, etc.) and communicate with digital pills, wearable devices, etc. It has been widely used in the field of medical health. However, when other devices access the Internet of Body on a large scale, there will be load imbalance caused by the difficulty in selecting the optimal route, which will affect the overall throughput and may even fail to transmit and endanger life. The traditional artificial intelligence routing algorithm cannot deal with the low model prediction accuracy and poor generalization ability caused by large noise and small data volume. This paper proposes an artificial intelligence routing algorithm, combines the variational autoencoder (VAE) and the generative adversarial network model (GAN) to construct a VAE-GAN model to generate multiple sets of data to achieve data enhancement on the Internet of Body. The optimization goals are to maximize the throughput of the Internet of Body and minimize the transmission cost. The entire routing problem is expressed as a Markov decision and the optimal transmission path is solved by learning previous historical experience to generate the real-time optimal route. Experiments have shown that this scheme can achieve the optimal route according to the transmission capacity of the real-time path and only requires fewer computing resources. It achieves load balancing of the entire network and avoids network congestion. The average throughput is much higher than that of traditional routing, and the advantage is more obvious under high load.

A texture enhanced attention model for defect detection in thermal protection materials

Efficacy and safety of sacituzumab tirumotecan monotherapy in patients with advanced urothelial carcinoma who progressed on or after prior anti-cancer therapies: Report from the phase 1/2 MK-2870-001 study.

796 Background: Sacituzumab tirumotecan (sac-TMT; also known as MK-2870/SKB264) is a TROP2 targeting ADC with a hydrolytically cleavable linker and a topoisomerase I inhibitor payload, KL610023 (average drug-to-antibody ratio, 7.4). In patients (pts) with urothelial carcinoma (UC), treatment with the anti-TROP2 ADC sacituzumab govitecan led to treatment-related grade ≥3 neutropenia in 35% of pts and febrile neutropenia in 10%. Cohort 9 of the MK-2870-001 (KL264-01; NCT04152499) evaluated sac-TMT monotherapy in pts with unresectable, locally advanced/metastatic UC who progressed on or after prior anti-cancer treatments. Methods: Eligible pts were ≥18 y, had histologically or cytologically confirmed locally advanced/metastatic UC, and had experienced PD on ≥1 prior line of platinum-based therapy. Platinum ineligible pts were eligible if they received prior anti-PD-(L)1 therapy; prior neoadjuvant/adjuvant therapy was counted as a line of therapy if pts progressed ≤12 mo of last dose. Pts must have ECOG PS of ≤1 and measurable disease by CT/MRI. Pts received sac-TMT 5 mg/kg Q2W until PD, unacceptable toxicity, or withdrawal of consent. Primary objective was ORR per RECIST v1.1 by investigator. Secondary objectives included DOR, PFS, OS, and safety. Results: 49 pts were treated by data cutoff (Jun 30, 2024) with a minimum follow-up of ≥9 wk (11 pts received sac-TMT as a second-line treatment; 38 received sac-TMT as a third-line or later treatment). Median age was 62 and 61 y, respectively; most pts were Asian (81.8%; 100%). Median follow-up was 9.5 mo (range, 7.5–16.2) and 11.7 mo (range, 7.8–17.4), respectively. By data cutoff, 7 (63.6%) and 29 (76.3%) pts, respectively, had discontinued treatment mostly due to PD (45.5%; 55.3%). Treatment-related grade ≥3 AEs occurred in 29/49 (59.2%) of pts, the most common (≥20%) of which were anemia (38.8%) and decreased neutrophil count (28.6 %). No treatment-related deaths were reported by safety data cutoff (May 21, 2024). Efficacy outcomes are shown in the Table. Conclusions: sac-TMT monotherapy had promising antitumor activity in pts with advanced UC who progressed on 1L platinum-based therapy. Clinical trial information: NCT04152499 . Outcome UC 2Lsac-TMT 5 mg/kg (n=11) UC 3L+sac-TMT 5 mg/kg(n=38) Confirmed ORR a n (%) 5 (45.5) 10 (26.3) 95% CI 16.7–76.6 13.4–43.1 CR n (%) 1 (9.1) 0 PR n (%) 4 (36.4) 10 (26.3) SD n (%) 3 (27.3) 17 (44.7) PD n (%) 2 (18.2) 10 (26.3) Not evaluable n (%) 1 (9.1) 1 (2.6) Median DOR b , months (range) NE (3.48+ to 13.86+) NE (2.10 to 14.95+) Median PFS b , months (95% CI) 5.78 (1.68–NE) 5.03 (3.52–7.39) Median OS b , months (95% CI) NE (2.0–NE) 11.5 (8.9–NE) NE, not evaluable. “+” indicates no progressive disease or death as of last disease assessment. a Includes all pts as-treated, and percentages are based on number of pts in each subgroup. b Based on Kaplan-Meier method for censored data.

Real-world treatment patterns and survival in men with metastatic castration-resistant prostate cancer (mCRPC) who previously progressed from metastatic hormone-sensitive prostate cancer (mHSPC) between 2020 to 2023 in the United States.

99 Background: While androgen deprivation therapy (ADT) is a backbone for managing mHSPC, therapies initially approved for mCRPC, such as androgen receptor pathways inhibitors like abiraterone (ABI) and non-ABI ARPIs ( enzalutamide, apalutamide, darolutamide), and/or docetaxel, are now guideline-recommended for use in mHSPC. Evidence on how this shift in mHSPC management affects current mCRPC treatment patterns and survival is lacking. Methods: A retrospective cohort of men treated for mCRPC between 2020-2023 was identified in the ConcertAI NLP360 oncology electronic medical records (EMR) database in the United States. Men with mCRPC were identified based on their first record for castration resistance after an earlier diagnosis of mHSPC. Men were required to have continuous EMR activity ≥12 months pre-mCRPC (baseline) and ≥6 months post-mCRPC. Line of therapy was identified as ABI, non-ABI ARPI, taxane-based chemotherapy, poly (ADP-ribose) polymerase inhibitors (PARPIs), immunotherapy (pembrolizumab, sipuleucel-T), radiopharmaceuticals (Ra-223, 177 Lu-PSMA-RLT), alone or in combination. Results: The cohort comprised 609 men with mCRPC who had progressed from mHSPC. Median age was 72 years (interquartile range: 66-79). Nearly 85% had ECOG 0-1, 79% had bone metastases, and 42% received bone-health agents during baseline. Most men had received ADT alone for mHSPC (53%), followed by ADT+ABI (19%), ADT+non-ABI ARPI (18%), and ADT+Docetaxel (10%). Overall, the most common first line treatment (1L Tx) for mCRPC was ARPI (62%; enzalutamide [28%] and ABI [25%]) and chemotherapy (22%). This trend was consistent in men with prior ADT for mHSPC. Among those who had received ADT+ARPI for mHSPC, sequentially ARPI as 1L Tx was common (most common on ADT+ABI and 2 nd most common among ADT+non-ABI ARPI). 1L chemotherapy use was more common among men with ADT+ARPI/DOC for mHSPC, compared to ADT alone (see Table 1), though was still less than 50% in the ADT+non-ABI ARPI group. Median real-world overall survival from 1L Tx was 21 months (95% confidence interval: 18, 25). Conclusions: With more than half of patients having received ADT alone in mHSPC, use of ARPIs was the most common 1L Tx option in mCRPC. Back-to-back use of ARPI upon progression to mCRPC was common. These findings highlight the need to explore alternative treatment option in mCRPC beyond ARPIs to improve survival in men with mCRPC. 1L mCRPC treatment patterns by prior mHSPC therapy. 1L Therapy Overall Prior mHSPC Therapy, n ADT ADT+ABI ADT+non-ABI ARPI ADT+DOC Cohort Size 609 320 (53%) 118 (19%) 109 (18%) 62 (10%) Non-ABI APRI 226 (37%) 138 59 7 22 ABI 153 (25%) 103 - 37 13 Chemotherapy 136 (22%) 38 38 45 15 Immunotherapy 28 (5%) 15 3 6 4 Radiopharmaceuticals 19 (3%) 7 3 6 3 PARPi 13 (2%) 4 4 3 2 Combination Therapy 34 (6%) 15 11 5 3

Association of localized high-risk prostate cancer (PC) and an androgen receptor low subpopulation susceptible to HER2 inhibition.

401 Background: Patients diagnosed with localized high-risk PC have higher rates of recurrence, and neoadjuvant intensive hormonal therapies seek to treat occult micrometastatic disease by addition to definitive treatment. We completed a phase 2 trial of neoadjuvant androgen deprivation therapy (ADT) plus the androgen receptor (AR) inhibitor enzalutamide (enza) for 6 months prior to radical prostatectomy (RP), in which 22 out of 37 patients exhibited poor pathologic responses (NCT02430480). In the current study, we aimed to identify targetable mechanisms of poor response evident in baseline biopsies that correlated with pathologic response. Methods: RNA-seq was performed on 147 laser microdissected foci from 99 biopsy blocks acquired prior to the initiation of neoadjuvant therapy. Pathologic response was measured directly from posttreatment RP H&amp;E slides. Differential expression was determined using linear mixed-effects models with histologic features and patients as random effects and residual cancer volume as a fixed effect. Differentially enriched pathways were identified using Ingenuity Pathway Analysis. Protein and phosphoprotein levels were measured in tissues using immunohistochemistry and analyzed using machine learning algorithms. Sensitivity and differential responses in cell lines and patient-derived organoids were measured using dose responsive curves, RNA-seq, single-cell sequencing and flow cytometry. Results: Gene signatures of higher AR activity were associated with exceptional responses (defined as less than 0.05 cm 3 of residual tumor in the RP), which was inversely associated with HER2 activity. High HER2 activity was associated with poorer outcomes. The inverse relationship between AR and HER2 activity was validated in three additional cohorts by RNA-seq and multiplex immunofluorescence. Tumors demonstrating resistance to ADT+enza expressed higher levels of HER2 and pHER2 protein at baseline. PC cell lines (including LNCaP and LAPC-4) treated with low doses of HER2 inhibitors (afatinib and neratinib) selected for populations with low AR activity as measured by RNA-seq, immunoblotting and flow cytometry. Combining enza+neratinib increased cell death, but patient-derived PC organoids exposed to 3-5 μM neratinib alone resulted in 90% cell death after 48h. Using single-cell sequencing and AR/HER2/PSA multiplex immunofluorescence, we found that most high-grade hormone-sensitive prostate tumors harbor a HER2-high subpopulation of cells with lower levels of AR activity that are resistant to AR inhibitors but sensitive to HER2 inhibition. Conclusions: Nascent human prostate tumors adopt an AR activity-low state prior to antiandrogen exposure that can be exploited by treatment with HER2 inhibitors, including novel combinations in the neoadjuvant or adjuvant setting. Future NCI clinical trials will evaluate such combinations. Clinical trial information: NCT02430480 .

Effect of enzalutamide on anticoagulant therapy with edoxaban in patients with prostate cancer.

148 Background: Enzalutamide is a potent androgen receptor signal inhibitor used in the treatment of various stages of prostate cancer. However, treatment with enzalutamide is challenging due to its high potential for drug-drug interactions, particularly in the typically older population of prostate cancer patients with often comorbidities treated with multiple drugs. Anticoagulants are such a class of drugs often co-administered with enzalutamide. While low-molecular-weight heparin can be safely combined with enzalutamide, the safety of combining enzalutamide with more patient-friendly direct oral anticoagulants remains uncertain. The objective of this study was to assess whether a drug-drug interaction exists between enzalutamide and edoxaban. Methods: A prospective, multicenter, open-label, two-arm parallel study was performed in men with prostate cancer who are treated with edoxaban, with and without enzalutamide. Plasma concentrations of edoxaban were measured at steady state. Pharmacokinetic (PK) parameters were calculated using non-compartmental analysis. Geometric mean ratios (GMR) of the area under the plasma concentration time curve over one dosing interval (AUC 0-24h ) were calculated. No clinically relevant interaction was defined if 90% of the confidence interval (CI) of the GMR was within the range of 0.8–1.25. Patients kept a patient diary to record medication intake and adverse events. Results: Sixteen patients with prostate cancer using edoxaban (eight patients with enzalutamide and eight patients without enzalutamide) were enrolled. Measured PK parameters are shown in the table. The exposure of edoxaban was similar when combined with enzalutamide, however the 90% CI fell outside of the 0.8-1.25 range (AUC 0–24h GMR 1.03; 90% CI 0.78 – 1.35). No adverse events were reported during the study. Conclusions: The average exposure of edoxaban was similar with and without enzalutamide. However, bioequivalence could not be established due to the broader than anticipated confidence interval. Despite this, the larger variability is not considered to have clinical consequences, supporting the safe co-administration of these drugs in clinical practice. Clinical trial information: NCT05339672 . Pharmacokinetic parameters edoxaban with and without enzalutamide (data are represented as geometric mean (CV%) [confidence interval]). Edoxaban + enzalutamide[90% CI] Edoxaban[90% CI] GMR [90% CI] Edoxaban AUC 0-24h (h*µg/L) 2034.72 (18%)[1711.71 – 2418.68] 1981.94 (47%)[1430.29 – 2746.36] 1.03[0.78 – 1.35] C max (µg/L) 304.30 (28%)[231.79 – 399.48] 254.91 (31%)[198.74 – 326.95] 1.19[0.91 – 1.57] C trough (µg/L) 18.93(37%)[14.12 – 25.37] 21.49 (97%)[11.00 – 41.98] 0.88[0.51 – 1.52] AUC 0-24h , area under the plasma concentration time-curve 0-24 hours; C max , maximum plasma concentration; C trough , trough plasma concentration; GMR, geometric mean ratio; CI, confidence interval; CV, coefficient of variation.

Characterization and reduction of RF loss up to 110 GHz by optimizing the UID-GaN layer in N-polar GaN material

In this work, the mechanism of RF loss up to 110 GHz for N-polar GaN has been studied. With the assistance of S-parameter characterization combined with secondary ion mass spectroscopy analyses, the incorporated oxygen impurity has been identified to be the main source bringing about the severe RF loss of N-polar GaN. The compensation of Fe-doping enables an effective reduction in RF loss. Moreover, the unintentionally doped (UID) GaN layer grown on top of the Fe-doped GaN buffer requires a careful design due to the distinct memory effect of Fe-doping in N-polar GaN. With an optimization of its thickness, a very low RF loss of 0.36 dB/mm at 94 GHz has been attained. Furthermore, by fitting the Fe concentration profile of UID-GaN according to the mass balance rate equation, it is found that the desorption of Fe on the N-polar GaN surface is significant. A bond-based model is introduced to elucidate the difference of the Fe memory effect between Ga-polar and N-polar GaN.

Modeling daily evapotranspiration time series based on Non-Linear Autoregressive Exogenous (NARX) method and climate variables for a data-deficient region

For flood-prone, developing nations where hydrological data is scarce, an innovative methodological approach is essential. This study aims to explore the potentiality of modelling daily evapotranspiration time series by checking causal relationship among the available climate variables in a flood-prone, data-deficient region like Samar in the Philippines. First, to verify if the available variables (rainfall, air pressure and the four (4) Niño Sea Surface Temperature (SST) Indices) have direct effects to evapotranspiration, a causality test called Convergent Cross-Mapping (CCM) was used. Interestingly, only the Niño SST indices and air pressure were found to have direct effects. Results showed that air pressure and the four (4) Niño SST Indices when combined with Non-Linear Autoregressive Exogenous (NARX) method, can effectively model evapotranspiration. This study raises a significant advancement in evapotranspiration modelling as it is the first to model and pinpoint the potentiality of causal relationship of air pressure and the four (4) Niño SST Indices to daily evapotranspiration time series. This method is found to be potentially suitable for disaster-prone regions where hydrological data is limited.

Advancing artemisinin resistance monitoring using a high sensitivity ddPCR assay for Pfkelch13 mutation detection in Asia

Immune checkpoint inhibitors (ICIs) in advanced upper tract urothelial cancer (UTUC) with mismatch repair deficiency (dMMR) or microsatellite instability (MSI).

818 Background: MSI-high (MSI-H) and dMMR are three times more common in UTUC than bladder cancer. While these features enhance ICI sensitivity in solid tumors, data on ICIs in advanced UTUC with dMMR/MSI-H remain scarce. Methods: We retrospectively reviewed records of patients (pts) with locally advanced (LA) or metastatic with dMMR/MSI-H UTUC treated with ICIs at MD Anderson (2015-2024). Descriptive statistics and the Kaplan-Meier method were used. Results: Twenty-four pts with LA/unresectable (n=8) or metastatic (n=16) disease were treated with ICIs (pembrolizumab, n=17; nivolumab, n=4; atezolizumab, n=3) (Table). Tumor origin was the ureter (10, 41.7%) or renal pelvis (14, 58.3%). Twenty-two (91.7%) pts had Lynch syndrome, mostly (n=20) detected by germline mutation testing ( MSH2 , n=12; MLH1 , n=5; MSH6 , n=3).Twenty-one (87.5%) pts had IHC-proven dMMR(MSH2/MSH6 loss, n=7; PMS2/MLH1 loss, n=5; MLH1 loss, n=4; MSH2 loss , n=3; MSH6 loss, n=3). The most frequent alterations in somatic genetic testing for 22 pts were MSH2 (12 pts), CREBBP (7 pts), ARID1A (7 pts) and NOTCH3 (7 pts). Fourteen (58.3%) pts received prior platinum chemotherapy: cisplatin (n=9) or carboplatin-based (n=5), with only 35.7% showing responses (one complete response [CR] and 4 partial responses [PR]).With a median follow-up of 54.3 months (mo) [95% CI: 19.5 – 87.1], median PFS was 55.8 mo [95% CI: 19.4 – NE]. Milestone PFS probabilities at 12 and 24 mo were 90.7% [95% CI: 79.2% – 100%] and 69.2% [95% CI: 51.3% – 93.4%], respectively.At a median follow-up of 51.3 mo [95% CI: 34 – 60.2], median OS was not reached. Median time on treatment was 13.5 mo [IQR: 4 – 25.8]. Eight (33.3%) pts remain progression-free beyond 4 years. ORR was 79.2%, including 16 CR (66.7%) and 3 PR (12.5%), while DCR was 95.8%.Median time to best response was 11.9 mo [IQR: 5.6 – 20]. Four (16.7%) pts were offered surgical consolidation with these outcomes: ypTaN0M0, ypT0N0M0, ypT1N0M0 and mypT1N0 M1-NED. Grade ≥3 immune-mediated toxicity events leading to ICI discontinuation (n=6) included hepatitis (n=3), pancytopenia (n=1), polyendocrinopathy (n=1) and diarrhea (n=1). Conclusions: Single-agentICIs show remarkable efficacy and durable responses in advanced dMMR/MSI-H UTUC, with one-third of pts remaining in remission after over 4 years. Our findings support dMMR/MSI-H as a predictive and prognostic biomarker in UTUC and the use of single-agent ICIs in this subpopulation. Variable Measure Age at dx of advanced disease, median [ICR] 66 [55.8 – 72.3] Sex, male (n, %) 14 (58.3%) Race/Ethnicity, n (%)  White 19 (79.2%)  Black 1 (4.2%)  Hispanic 2 (8.3%)  Asian 2 (8.3%) Urothelial carcinoma mixed with variant histology, n (%) 3 (12.5%) Liver mets at ICI start, n (%) 2 (8.3%) Bone mets at ICI start, n (%) 5 (20.8%) Hemoglobin &lt;10 g/dL at ICI start, n (%) 5 (20.8%) Bellmunt score, n (%)  0-1 19 (79.2%)  2 3 (12.5%)  3 2 (8.3%)

Patient and caregiver preferences for the treatment of locally advanced or metastatic urothelial carcinoma (la/mUC): Results of a targeted literature review (TLR).

755 Background: The treatment landscape for la/mUC has evolved with multiple care options available. As new therapies are adopted, decision-making among physicians, patients, and their caregivers becomes more complex and challenging. This study summarizes the existing literature on preferences of patients and caregivers about aspects of treatment following a diagnosis of la/mUC. Methods: A TLR of English-language conference abstracts and full-text manuscripts published from 2015 was conducted using Embase and PubMed, to identify qualitative and quantitative studies on the treatment preferences of patients with la/mUC and caregivers of people with la/mUC. Literature was independently screened against predefined eligibility criteria by two researchers, with a third researcher resolving disagreements. Results: Data from 13 publications were extracted (n=10 [77%] qualitative, n=3 [23%] quantitative); of these, 6 (46%) were full-text manuscripts and 7 (54%) were conference abstracts/posters. When specified, most studies (6/10 [60%]) were conducted in the US. Six studies (46%) assessed preferences among both patients and caregivers. The quantitative preference studies assessed varied efficacy endpoints, including overall survival (n=2), overall response rate (ORR; n=1), and progression-free survival (n=1). Treatment efficacy was the most important consideration in 2 quantitative studies, while 1 study found adverse events (AEs), combined with number and duration of medicines, to be more important to patients. Across publications, attributes related to treatment AEs significantly impacted preferences. Unmet needs related to symptoms and AEs were identified. The symptoms/AEs reported most frequently across all 13 studies were fatigue (n=7 [53%]), cancer-related pain (n=6 [46%]), peripheral neuropathy (PN; n=3 [23%]), blood in urine (n=3 [23%]), and nausea (n=3 [23%]). In 1 quantitative study, cancer-related pain was ranked as the second most important treatment attribute after ORR. Patients in this study also indicated that they would accept a 7.8% reduction in ORR to reduce the risk of developing PN by 10%. Of 3 studies that compared differences between patient and caregiver preferences, 2 quantitative studies found that caregivers placed a higher importance on avoiding side effects than patients. Conclusions: Despite heterogeneity in study designs and outcomes reported, patients and caregivers often prioritized treatment efficacy over tolerability. However, in quantitative studies, patients and caregivers were willing to accept lower efficacy for a more tolerable treatment, although the magnitude of trade-offs varied by AE. Such insights highlight the importance of incorporating patient and caregiver preferences in shared decision-making and personalizing treatment according to individual patient goals.

Impact of concomitant medication use on treatment outcomes in patients with RCC treated with immune checkpoint inhibitors.

603 Background: Multiple studies on various cancer types have investigated concomitant statin, aspirin, and metformin use with immune checkpoint inhibitors. While some found improved OS and PFS, others reported no significant effect. In RCC, a retrospective study linked statins with improved OS and PFS. We aimed to evaluate the impact of statin, aspirin, and metformin use on survival in RCC patients treated with ICIs. Methods: A retrospective analysis was conducted on adult patients with advanced RCC treated with ICIs at Emory Winship Cancer Institute between 2018 and 2024. Concomitant medication use was assessed via chart review during active ICI treatment. Clinical benefit (CB) is determined by stable disease, partial response, and complete response. The multivariate analysis model for statin was built by controlling the age, gender, race, smoking status, IMDC risk group, ECOG PS, clear cell histology, prior treatments, and liver metastases. Variables were subject to backward elimination at the significant level of p &lt; 0.2. Results: Data from 400 patients were analyzed, with a median follow-up of 43.0 months (95% CI: 36.6-51.4). Of 400 patients, 138 (34.5%) were treated with ICI monotherapy, 131 (32.8%) treated with dual ICI combination, and 114 (28.5%) were treated with ICI and TKI combinations. 85 (21.3%) of the patients were African American or Black, 284 (71%) of them were White, and 239 (59.8%) were treated with ICIs as first-line. Statin use was more common among patients without prior treatment, without liver metastasis, older individuals, and those with a BMI ≥24.9. In univariate analysis, statin use showed potential associations with longer OS (HR 0.82; 95% CI 0.62-1.07 p=0.144), longer PFS (HR 0.81; 95% CI 0.64-1.02 p=0.071), and a higher likelihood of receiving CB (OR 1.85; 95% CI 1.17-2.92 p=0.008). However, multivariate analysis did not confirm significant differences in survival or CB. Survival outcomes are summarized in the table. Conclusions: Our analysis found no significant impact of concomitant statin, aspirin, or metformin use on RCC patient outcomes treated with ICIs. Further advancements in our understanding of tumor biology and checkpoint inhibitors might explain how concomitant medication affects treatment outcomes. Our study is limited by its retrospective design, and future prospective trials are necessary to provide definitive evidence. Univariate analysis of survival outcomes and clinical benefit. Overall Survival Progression-free survival Clinical Benefit HR (95% CI) p-value HR (95% CI) p-value OR (95% CI) p-value Statin Y n=170 0.82 (0.62-1.07) 0.144 0.81 (0.64-1.02) 0.071 1.85 (1.17-2.92) 0.008 Statin N n=230 - - - - - - Aspirin Y n=138 0.93 (0.70-1.24) 0.623 0.84 (0.66-1.07) 0.159 1.49 (0.93-2.40) 0.100 Aspirin N n=262 - - - - - - Metformin Y n=49 1.04 (0.68-1.57) 0.860 0.80 (0.55-1.15) 0.231 1.37 (0.68-2.78) 0.379 Metformin N n=351 - - - - -

Rates of first next-generation sequencing (NGS) testing at the end of life in patients (pts) with advanced urothelial carcinoma (aUC).

727 Background: Despite the availability of targeted therapies like erdafitinib for pts with aUC with susceptible genomic alterations, the rate of NGS testing remains low at 32% in the United States (Hage Chehade...Swami, JAMA Network Open, 2024). Furthermore, limited data exist regarding the timing of NGS testing in relation to the time of death. Herein, we sought to assess the rates of NGS testing at the end of life in pts with aUC in a real-world patient population. Methods: A de-identified nationwide Flatiron Health electronic health record (EHR)-derived database was used to extract patient-level data. Inclusion criteria: pts who received NGS testing (blood/tissue) and who had a date of death recorded. The analytic cohort included pts diagnosed with aUC between 1/1/2011 and 11/14/2022 who received first NGS testing results between 5/3/2012 and 12/21/2022. The time difference between each pt’s first NGS result delivered and death was calculated, and thereafter, pts were categorized into 3 categories: pts receiving results &gt; 3 months (mo) before death, within 3 mo of death, or after death. The frequency and percentages of the 3 categories were reported, as well as by year of death. The percentages in each category were compared between 2019 (year of erdafitinib approval) and 2022 (last year in dataset) to evaluate changes in NGS testing trend. Results: Among 12,157 pts with aUC in the dataset, 1,637 had both a recorded date of death and underwent NGS testing, and were eligible and included in final analysis. The median age was 72 (IQR 66 – 79). The majority were male (73%), White non-Hispanic (76%), and treated in community practice (86%). 68.2% received NGS results &gt; 3 mo before death (n = 1,117), 28.3% received results within 3 mo of death (n = 464), and 3.4% of NGS results were reported after death (n = 56). In pts who died in 2019 versus 2022, the percentage of pts receiving NGS results &gt; 3 mo before death increased from 61% to 75%, while the percentage of pts receiving results within 3 months decreased from 33% to 22%, and the percentage of NGS results reported after death declined from 5.2 to 2.7%. Baseline characteristics (including race-ethnicity, insurance plan, practice type [academic vs. community]) in these categories will be presented at the meeting. Conclusions: Our findings suggest that a sizeable number of pts with aUC (∼ 32%) received their first NGS testing results towards the end of life, highlighting the need to integrate genomic testing earlier during the course of the disease to optimize benefit with targeted therapies. These results could inform clinical practice and therapeutic decisions in the clinic. CHC, YJ: Equal contribution; US, NA: Senior authors.

Spin wave propagation in YIG waveguides with magnetic microvolcanoes: Experiment and simulation

Control of spin wave transport in polymer 3D films was realized by magnetic microvolcanoes embedded in waveguides, fabricated by soft-matter specific techniques. Propagate of the spin wave signal excited in yttrium iron garnet (YIG) with 3D self-standing microvolcanoes chambers on top filled by the magnetic nanoparticles was evaluated by Brillouin light scattering and microwave spectroscopy. The magnetic moment of the polymer microvolcanoes varied with the change of the magnetic field bias direction inside the YIG films, which was shown by 2D mapping of the outer surface of the films. The good correlation of micromagnetic modeling and experimental data of spin wave propagation in the multistructure as a function of the applied magnetic field was clarified by the convergence parameters of the obtained polymer 3D magnetic microvolcanoes fields and the standard theory of spin wave propagation. The uniqueness of the soft materials object—polymer magnetic 3D films on conductive YIG film—lies in the application of the magnon network properties, which may find application in biomedical high-sensitivity feedback sensors.

PCK1 and SLC22A2 gene variants associated with response to metformin treatment in type 2 diabetes

Type 2 diabetes (T2D) is a chronic disorder affecting 462 million worldwide, often managed with metformin as first-line treatment. However, metformin’s response varies among individuals, including up to 30% experiencing serious adverse drug reactions (ADRs) and 20-50% inefficacy. These differences may be due to various factors, including pharmacogenetic (PGx) variants. The PGx variants documented so far could affect both the safety and efficacy of metformin, but due to a lack of replication studies, none reached the clinical evidence-level needed to be used as a predictive marker for treatment response. Therefore, this study aims to evaluate the association between the presence of candidate PGx variants and metformin response in T2D subjects. We conducted an association study involving 108 T2D participants currently or previously treated with metformin. A characterization of their therapeutic response was carried out through questionnaires and pharmacological profile reviews. DNA samples were collected during their single visit to perform genotyping of 24 selected candidate PGx variants. Association analyses between candidate PGx variants and metformin response were performed. Among the subjects included in the analyses (n =  84), 25% were non-responders, and 58% experienced ADRs. At the time of study enrollment, 93.9% of non-responders continued to use metformin. The odds of being a non-responder to metformin are 5.6 times higher for homozygous carriers of the alternative allele of a variant within the PCK1 gene (rs4810083) compared to the other genotypes (95% interval confidence [1.9–16.6]). Two variants in perfect linkage disequilibrium within the SLC22A2 gene (rs316019 and rs316009) were associated with increase odds of having ADRs, where homozygous genotype carriers are 7.3 times more likely to have ADRs presentation (95% interval confidence [1.85–29.01]). This study identified associations between PCK1 and SLC22A2 candidate PGx variants and metformin response in T2D treatment. Additional genetic and functional studies are necessary to elucidate the variants’ impact in metformin’s pharmacological mechanisms.

Assessment of the environmental impacts of regional groundwater flow path fluctuations in the water-stressed drought prone Northern Region of Bangladesh

A phase 1, first-in-human, dose escalation and expansion study to evaluate the safety and tolerability of XmAb541 (claudin-6 x CD3) T-cell engaging bispecific antibody in subjects with germ cell tumors and other advanced solid tumors.

TPS652 Background: Claudin-6 (CLDN6) is overexpressed in solid tumors including germ cell tumors (GCTs) with minimal expression in healthy tissue. This differential expression profile makes CLDN6 a suitable tumor-associated antigen for a T-cell engaging bispecific antibody (bsAb). XmAb541 is a first-in-class humanized, anti-CLDN6 x anti-CD3 bsAb that directs T-cell cytotoxicity. The XmAb 2+1 format provides avid tumor targeting and selectivity. Importantly, XmAb541 selectively binds CLDN6, with reduced binding to other claudin family proteins (e.g., CLDN9) and non-CLDN6-expressing healthy tissue [1]. This study focuses on subjects with GCT and other CLDN6+ solid tumors who have failed standard therapy and have a high unmet medical need. The primary objective of the trial is to determine an optimal and tolerated dose(s) for further evaluation. Methods: This is a first-in-human, Phase 1, open-label study to evaluate the safety and tolerability of XmAb541 in advanced solid tumors. The study will be conducted in 2 Parts. Part 1, Dose Escalation, will establish a dosing regimen inclusive of a priming dose, step-up dose(s), and the target dose. Part 2 Dose Expansion will further evaluate safety and tolerability and provide an initial evaluation of preliminary antitumor activity for the dose regimen(s) established in Part 1. XmAb541 will be administered intravenously. Key inclusion criteria are age ≥ 18 years (for subjects with GCTs, age ≥15 years). Have histological evidence of locally advanced, recurrent, or metastatic GCT, ovarian, fallopian tube, peritoneal cancer, or adenocarcinoma of the endometrium. Have documented progressive disease on standard-of-care therapies; exhausted therapies with a survival benefit, or the standard therapy has no survival benefit or proven to be ineffective, intolerable, or subject is not a candidate for such available therapy. Subjects must have an Eastern Cooperative Oncology Group performance status of 0-2 and a life expectancy ≥ 3 months with adequate liver, kidney, and bone marrow function. Key exclusion criteria include the following: known active central nervous system metastases and/or carcinomatous meningitis. Subjects with treated brain metastases may participate, provided they are radiologically stable. Ethics approval: This study was approved by WCG IRB. References: 1. Faber, M. Bispecific claudin-6 x CD3 antibodies in a 2+1 format demonstrate selectivity and activity on human ovarian cancer cells. (AACR 2021, Abstract No. 1860). Clinical trial information: NCT06276491 .

Real-world effectiveness and safety of first-line (1L) avelumab + axitinib in patients with advanced renal cell carcinoma (aRCC): Primary analysis of the AVION study.

474 Background: In the JAVELIN Renal 101 phase 3 trial, 1L avelumab + axitinib resulted in significantly longer progression-free survival (PFS) and a higher objective response rate (ORR) vs sunitinib in patients with aRCC, with an acceptable safety profile. The AVION study is evaluating the effectiveness and safety of avelumab + axitinib in routine clinical practice in various countries. We report data from the primary analysis. Methods: AVION is a prospective noninterventional study of patients with aRCC receiving 1L avelumab + axitinib in Germany, Greece, Belgium, or Russia. Patients are observed for 24 months. The primary objective is to evaluate the overall survival (OS) rate at 12 months. Secondary objectives include evaluation of OS rate at 24 months, median OS, PFS, ORR, duration of response (DOR), and safety. Results: By data cutoff (Jul 5, 2024), 104 patients were analyzed. Median age was 70 years (range, 37-87) and 70.2% were male. ECOG PS was 0-1 in 92.3%, 2 in 6.7%, and not reported (NR) in 1.0%. International Metastatic RCC Database Consortium (IMDC) risk group was favorable, intermediate, poor, and NR in 26.0%, 45.2%, 12.5%, and 16.3%, respectively. Tumor histology was clear cell, sarcomatoid, and other in 89.4%, 3.8%, and 6.7%, respectively. Prior anticancer treatment included adjuvant drug treatment, surgery (nephrectomy), or radiotherapy in 3.8%, 75.0% (66.3%), and 8.7%, respectively. At data cutoff, avelumab or axitinib treatment was ongoing in 21 (20.0%). Median OS was not reached (95% CI, not estimable [NE]) and the 12-month OS rate was 82.7% (95% CI, 73.5-88.9). Median PFS (95% CI) was 11.3 months (8.1-NE) and 6- and 12-month PFS rates (95% CI) were 72.5% (62.1-80.5) and 48.4% (37.5-58.5), respectively. Among 87 patients with available response data (assessed up to 12 months), ORR was 46.0% (95% CI, 35.2-57.0), comprising complete or partial response in 4.6% and 41.4%, respectively; disease control rate was 79.3% (95% CI, 69.3-87.3); and median DOR was not reached. Treatment-related adverse events (TRAEs) occurred in 67.3% and were grade ≥3 or serious in 20.2% and 14.4%, respectively. TRAEs led to permanent discontinuation of avelumab or axitinib in 6.7% or 9.6%, respectively, and led to death in 1.0%. The most common TRAEs of any grade (≥6%) were diarrhea (19.2%), fatigue (13.5%), hypothyroidism (8.7%), and nausea (7.7%). Follow-up is ongoing. Conclusions: Results from the AVION study are generally consistent with JAVELIN Renal 101 and previous observational studies, demonstrating the effectiveness, safety, and favorable tolerability with low discontinuation rates of avelumab + axitinib in a heterogeneous real-world population.

Overall survival and quality of life with [ ¹⁷⁷ Lu] Lu-PSMA-617 plus enzalutamide versus enzalutamide alone in poor-risk, metastatic, castration-resistant prostate cancer in ENZA-p (ANZUP 1901).

17 Background: Interim analysis of ENZA-p with median follow-up 20 months showed improved PSA-progression-free survival (PFS) and depth of PSA-response with the addition of [ 177 Lu]Lu-PSMA-617 (LuPSMA) to enzalutamide (enza) as first-line treatment of poor-risk, metastatic, castration-resistant prostate cancer (mCRPC). Here we report effects on overall survival (OS) and health-related quality of life (HRQL) with longer follow-up. Methods: We randomly assigned 162 participants (pts) to enza 160 mg daily alone, or in combination with (2 or 4 doses) LuPSMA 7.5 GBq. Eligible pts had mCRPC not previously treated with chemotherapy or an androgen receptor pathway inhibitor for mCRPC, 68 Ga-PSMA PET-avid disease, and at least 2 risk factors for early disease progression on enza-alone. HRQL was to be rated with the EORTC core quality-of-life questionnaire every 6 weeks until radiological progression. Deterioration-free survival was from random assignment until the earliest of death, clinical progression, discontinuation of study treatment, or a worsening of 10 points or more from baseline in physical function, or in overall health and quality of life (OHQL). HRQL scores were analyzed with repeated measures modelling to calculate group means and differences. HRQL scores range from 0 (lowest possible) to 100 (highest possible). Time to event data were analysed with the Kaplan-Meier method, stratified log rank test, and stratified Cox-proportional hazards regression. Analyses of these secondary endpoints were specified a priori and are by intention to treat. P-values and confidence intervals are 2-sided without adjustment for multiple comparisons. Results: A total of 96 deaths were reported after a median follow-up of 34 months (IQR 29-39): 53 among those assigned enza-alone and 43 among those assigned enza+LuPSMA. OS was longer in the enza +LuPSMA group than the enza-alone group (median months 34 vs 26; HR 0.55, 95% CI 0.36 to 0.84; p=0.005). 30 of 79(38%) in the enza-alone arm received subsequent LuPSMA off trial. HRQL was rated by 154 of 162 pts (95%). Deterioration-free survival rates at 12 months, and stratified log-rank p-values favored enza+LuPSMA for both OHQL (40% v 13%; p &lt;0.001), and for physical function (38% v 17%; p &lt;0.001). Mean scores for pain until progression favoured the enza+LuPSMA group over the enza-alone group (difference 7.2, 95% CI 1.6 to 13; p=0.01). Mean scores for fatigue until progression favoured the enza+LuPSMA group over the enza-alone group (difference 5.9, 95% CI 1.1 to 10.7; p=0.02). The frequency of self-rated xerostomia was lower in the enza-alone group (74% vs. 57%; p=0.04). Conclusions: The addition of LuPSMA to enzalutamide in poor risk mCRPC improved overall survival, scores for both pain and fatigue, and deterioration-free survival for both physical function and for OHQL. Clinical trial information: NCT04419402 .