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Phase 1 safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of pasritamig in Asian population with metastatic castration-resistant prostate cancer (mCRPC).

172 Background: Pasritamig is a first-in-class bispecific antibody T-cell engager that simultaneously binds human kallikrein 2 (KLK2) on PC cells and CD3 receptor complexes on T cells. Tolerable safety profile and promising anti-tumor activity was reported for US & EU population. We report results for the Asian mCRPC population from a first-in-human study (NCT04898634) evaluating pasritamig in patients with advanced PC. Methods: The RP2D dose schedule of 3.5mg (step-up dose 1)-18mg (step-up dose 2)-300mg IV Q6W was administered. Pre-medication with dexamethasone (16 mg) was implemented for step-up and first treatment dose. The primary objective was safety. Secondary objectives included preliminary antitumor activity, PK and PD. Results: As of July 4, 2025, 22 Asian patients (17 Chinese, 5 Japanese, median [range] age 69 [52-85] years), with a median of 3 prior therapies (range 2-6; 100.0% ARPI, 95.5% taxane, 22.7% PARPi, 4.5% RLT), received at least 1 pasritamig dose. Fifteen patients had bone and/or lymph node metastasis only while the other 7 patients had visceral metastasis. No DLTs, pasritamig-related deaths or treatment discontinuations were reported. Sixteen (72.7%) patients reported ≥1 treatment-related AE (TRAE), and 8 (36.4%) patients experienced Grade ≥3 TRAE. Most (7/8) Grade ≥ 3 TRAEs were cytopenia (5 lymphopenia, 2 anemia), of which the majority (5/7) already had Grade 2 cytopenia at baseline. The other Grade 3 TRAE was dermatitis, which recovered in 22 days with steroid treatment. Two (9.1%) CRS cases were reported with the severity of Grade 1. No infusion-related reactions or ICANS were observed. The PSA50 response was 50.0% (10/20), including 4 responders with visceral metastases, and confirmed PSA50 was 35.0% (7/20) in the PSA-evaluable population. With a median follow up of 2.7 months, median rPFS was still not reached (95% CI: 1.81, NE) with 68.2% (15/22) patients ongoing. ORR in the patients with measurable disease was 11.1% (1/9), with response at a site of liver metastasis. PK was linear with a mean half-life of 14 days. Biomarker assessment revealed an elevated on-treatment IL-6 level in a patient who had Grade 1 CRS. Increases in on-treatment IFN-γ and CD38+/CD8+ T-cells were observed following pasritamig treatment, indicating peripheral T-cell activation consistent with the proposed MOA. A higher baseline frequency of PD-1+/CD8+ T-cells was noted in PSA50 responders. Conclusions: The safety, efficacy, PK and PD profile of pasritamig in Asia is broadly consistent with the US & EU population reported previously. Longer follow up for efficacy and further quantification of responses in visceral lesions are in progress. These results highlight the potential of pasritamig to fulfill the unmet need for a safe T-cell based therapy for mCRPC and support the inclusion of Asian patients in global phase 3 trials. Clinical trial information: NCT04898634 .

Impact of neoadjuvant chemotherapy on outcomes of bladder-preserving chemoradiotherapy in muscle-invasive bladder cancer.

670 Background: NAC (neoadjuvant chemotherapy) has been established as the standard of care for patients with MIBC (muscle-invasive bladder cancer) undergoing radical cystectomy. However, its potential benefit prior to CCRT (concurrent chemoradiotherapy) remains largely unexplored. Methods: This retrospective analysis included 226 patients with clinical stage T2–4N0–1M0 MIBC treated at three university centers between January 2012 and December 2024. Among them, 170 received upfront CCRT, and 56 received NAC followed by CCRT. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), metastasis-free survival (MFS), and cystectomy-free survival (CFS). Results: Patients who received NAC were younger (mean age, 68 vs. 75 years; p < 0.001) and more likely to have N1 disease (16.1% vs. 4.1%; p = 0.005) compared with those treated with upfront CCRT. During a median follow-up of 83.7 months (95% confidence interval [CI], 66.0–101.4 months), 73 deaths were observed. CFS did not differ according to the receipt of NAC (p = 0.415). However, NAC was significantly associated with improved OS (hazard ratio [HR], 0.318; 95% CI, 0.163–0.620; p < 0.001), PFS (HR, 0.663; 95% CI, 0.442–0.994; p = 0.047), and MFS (HR, 0.444; 95% CI, 0.226–0.870; p = 0.018). After adjustment using inverse probability of treatment weighting (IPTW) including age, sex, ECOG performance status, histology, clinical T and N stage, tumor multiplicity, presence of carcinoma in situ, hydronephrosis, maximal transurethral resection of bladder tumor (TURBT) status, and radiation field, the survival benefit of NAC remained consistent for OS (HR, 0.272; 95% CI, 0.125–0.594; p = 0.001), PFS (HR, 0.543; 95% CI, 0.349–0.843; p = 0.007), and MFS (HR, 0.443; 95% CI, 0.224–0.877; p = 0.020). Conclusions: This multi-institutional study provides evidence that NAC before CCRT is associated with improved survival outcomes in patients with MIBC undergoing bladder-preserving treatment with curative intent.

Genomic landscape of metastatic urothelial cancer in a multicenter Argentine cohort.

789 Background: Metastatic urothelial carcinoma (mUC) is a lethal disease with a heterogeneous genomic landscape. Most available genomic data derive from North America, Europe, or Asia, with Latin American (LATAM) patients largely underrepresented. Region-specific data are needed to inform precision oncology efforts and expand access to biomarker-driven trials. Methods: We conducted a retrospective, multicenter cohort study of patients with mUC who underwent genomic testing. Patients were included from eight academic and community centers across Argentina. Results: A total of 101 patients were included. Nearly half (45.5%; n = 46) presented with stage IV disease. Somatic mutation profiling was performed in all patients (100%) using multigene panel analysis. A potentially targetable mutation was identified in 63.4% (n = 64) of patients, while an ESCAT tier I alteration was detected in 33.7% (n = 34). FGFR2/3 alterations were observed in 24.7% (n = 25), HER2 amplification in 8.9% (n = 9), and PIK3CA mutations in 10.9% (n = 11). Only four patients with FGFR2/3 alterations received erdafitinib. With a median follow-up of 11.5 months (IQR, 14–19.1), the median progression-free survival (PFS) was 12.5 months (95% CI, 8.3–17.7), and the median overall survival (OS) was 24.2 months (95% CI, 16.3–NR). No statistically significant differences in PFS or OS were observed between patients with ESCAT alterations and those without (PFS: 8.3 vs 25.0 months, p = 0.08; OS: not reached vs 18.0 months, p = 0.39). Conclusions: This study provides one of the largest real-world genomic datasets of mUC in LATAM, underscoring the underrepresentation of patients from this region in genomic research. These findings highlight the need to improve access to biomarker-driven trials and precision oncology initiatives in Latin America.

Analog Control of Reconfigurable GHz Resonances from Chiral Spin Texture Ensembles

ABSTRACT Gigahertz excitations of magnetic films are widely explored for energy‐efficient, high‐frequency microelectronics. The advent of nanoscale chiral spin textures (CSTs) with topological dynamics promises novel resonance characteristics. However, prior works on technologically relevant chiral multilayers encountered key material constraints, precluding the realization of functional CST resonances. We address this by engineering a minimally damped, strongly chiral multilayer with a robust broadband resonance spectrum. Microwave spectroscopy, Lorentz microscopy, and simulations elucidate contrasting resonance features on either side of zero magnetic field arising from distinct irreversible CST transitions. A simple analytical model can quantitatively describe these robust inter‐textural resonances over the entire field‐frequency range. Crucially, in situ CST reconfigurability enables analog tunability of the resonant dispersion ‐ with wide‐band, deterministic, non‐linear (or linear) modulation via the input knob. Our work unlocks the microwave potential of multilayer CSTs by leveraging their unique thermodynamics. It opens the door to fabrication‐free reconfigurable magnonics, toward broadband transmission and unconventional computing.

Single‐Fiber Design for Higher Performance Artificial Muscles

ABSTRACT Artificial muscles are essential components in the advancement of next‐generation soft robotics, biomedical devices, and adaptive wearables. While conventional fiber‐based actuators often rely on multi‐material assemblies and complex interfacial engineering, their performance is limited by structural heterogeneity and low‐efficient energy coupling. This review highlights the emerging paradigm of single‐fiber or in‐fiber artificial muscle design, where actuation functionality is intrinsically encoded within the molecular architecture of individual fibers. We comprehensively examine state‐of‐the‐art material systems such as phase‐transition materials, block copolymer self‐assemblies, mechanically interlocked polymers, covalent supramolecular hybrids, and woven polymer networks. Particular emphasis is placed on the structure–property–function relationships that govern the actuation strain, stress output, response speed, and long‐term durability. We also propose a unified framework for evaluating single fiber actuator performance based on key metrics and critically discuss manufacturing challenges, scalability, and integration with smart sensing system. This review provides a roadmap for molecular design of the high‐performance artificial muscle, offering new strategies for intelligent actuation and soft material systems in real‐world applications.

A prospective study exploring genomic correlates of clinical outcome in patients with metastatic castration-sensitive prostate cancer receiving enzalutamide.

244 Background: The genomic landscape of metastatic castration-sensitive prostate cancer (mCSPC) in Asian populations remains poorly characterized. Epidemiological studies have shown that while the incidence and mortality of prostate cancer are lower in Asian men compared to Western populations, Asian patients often present with higher-grade tumors at diagnosis. Furthermore, Asian men may exhibit comparable or even superior survival outcomes in response to androgen deprivation therapy (ADT), suggesting potential ethnic differences in tumor biology. This study investigated somatic alterations and their association with clinical outcomes in Japanese patients with mCSPC receiving ADT plus enzalutamide. Methods: We conducted a prospective, multicenter study of Japanese mCSPC patients treated with ADT plus enzalutamide. Tumor biopsy specimens obtained from 76 Japanese patients with mCSPC were analyzed by whole-exome sequencing. Somatic mutations were identified using the Genomon pipeline with matched germline DNA. The primary endpoint was time to castration-resistant prostate cancer (CRPC) progression, assessed by Kaplan-Meier survival analysis and Cox proportional hazard models. Results: Over a median follow-up of 29 months, 22 of 76 patients (29%) progressed to CRPC. FOXA1 emerged as the most frequently mutated gene (36%), followed by CYB561D1 (32%). Twenty genes were mutated in 10% or more of cases. Hotspot clustering was observed in 17 genes. BIRC5 (HR 4.09, 95 CI 1.70-9.80, p<0.01) and DUOXA1 (HR 3.18, 95% CI 1.17-8.64, p=0.02) hotspot mutations were significantly associated with time to CRPC in the univariate analysis. In contrast, FOXA1 wing2 domain mutations were associated with favorable prognosis (HR 0.22, 0.05-0.93, p=0.04). Additionally, EOD grade ≥ 3 was a clinical predictor of early progression (HR 4.19, 1.75-10.04, p=0.01). Multivariate analysis confirmed BIRC5 hotspot mutation (HR 3.71, 1.17-11.81, p=0.03) as an independent predictor of CRPC progression. Conclusions: This prospective genomic study revealed a somatic mutation profile derived from Japanese mCSPC. The BIRC5 hotspot mutation was identified as a novel predictor of CRPC progression in patients with mCSPC receiving androgen signaling inhibitors.

End-of-life care preferences in penile cancer patients: Shifting patterns and disparities over two decades.

5 Background: Penile cancer (PC) is often diagnosed late, which leads to advanced disease. Studies have reported that less than 18% of individuals with metastatic PC receive any kind of palliative therapy. Place of Death (PoD) is a crucial determinant of patient and caregiver preferences and the cost of caregiving at the end of life (EOL). We aimed to evaluate the trends in PoD for patients with PC in the U.S. from 2003 to 2023 based on the CDC WONDER (Wide-ranging Online Data for Epidemiologic Research) database. Methods: We analyzed data from January 01, 2003, to December 31, 2023. The data for deaths due to PC were pooled using the International Classification of Diseases-10th Revision code as C60 for malignant neoplasm of the penis. The inclusion criteria included patients aged > 25 years. PoD is defined as deaths at home and hospice (H&H) versus medical facilities. Average annual percentage change (AAPC) was calculated using the Joinpoint Regression Program, version 5.0.2. Results: The analysis demonstrated a total of n = 6,074 deaths from PC. A total of 52.1% of deaths, n = 3,167, were reported at H&H. The trend analysis demonstrates an exponential rise in H&H utilization from 34.4% in 2003 to 57.5% in 2023, AAPC [5.4284, CI (4.7-6.10, p < 0.000001]. A significant increase in the utilization of H&H is notable in both African Americans (AA), AAPC [2.8514, CI (1.0-4.7), p = 0.004], and the White population, AAPC [5.3497, CI (4.6-6.0); p < 0.000001]. However, a racial disparity is also noted, with 45.4% in AA, while the White population is at 52.5% deaths in H&H-based care. PC mortality in medical facilities has a 29.7% decline from 2003 to 2023. On age stratification, there was a significant increase in utilizing H&H as PoD for the 45-64 years cohort AAPC [4.29, CI (3.2, 5.2), p < 0.000001], similarly, with the older age group 65+ cohorts AAPC [6.26, CI (5.4, 7.0), p < 0.000001]. In contrast, the younger cohort deduced no significant trend AAPC [2.92, CI (-1.5, 7.6), p = 0.14]. Conclusions: This is the first study to our knowledge providing valuable insights into the evolving PoD preferences among PC patients in the U.S.The age-related trends underscore the importance of tailoring end-of-life care strategies to specific age cohorts. The findings emphasize the importance of policies promoting and supporting H&H care for PC patients. Targeted efforts are warranted to address notable disparities in PoD preferences among racial and age groups.

Effect of censorship in the interpretation of outcomes of the enfortumab vedotin plus pembrolizumab EV-302 phase 3 randomized clinical trial.

781 Background: The purpose of this study was to assess whether the high treatment discontinuation rate in the chemotherapy arm of the EV-302 trial could bias survival outcomes. The EV-302 trial demonstrated very significant overall survival (OS) benefit for the Enfortumab Vedotin plus Pembrolizumab (EVP) relative to standard chemotherapy (CHT) for patients with metastatic urothelial carcinoma. However, questions have been raised regarding the high rate of treatment discontinuation in the CHT arm for reasons unrelated to adverse events or progression (33% vs. 10% with EVP, P < .01), potentially resulting in loss of unaccounted information, or informative censoring, and affecting survival results interpretation. Methods: We performed a multistep analysis to assess the impact of differential dropout on trial outcomes. First, Kaplan–Meier (KM) curves were reconstructed from published data to estimate time-to-event outcomes. Second, a reverse KM analysis was conducted to evaluate censoring patterns in the overall population and key subgroups (PD-L1 expression; cisplatin eligibility). Third, simulation models were employed to test whether informative censoring could negatively impact survival benefit by EVP. Results: No significant imbalance in censoring between the treatment arms of EV-302 was found on reverse KM analysis when assessing OS ( P = .73). However, a significant difference was noted for progression-free survival (PFS) ( P = .002). Conclusions: Simulation analysis revealed that even under extreme assumptions of informative censoring, the OS benefit of EVP remained statistically significant. Despite the high discontinuation rate in the CHT arm, OS benefit with the treatment EVP group remains robust. These findings support the reliability of EVP as a first-line treatment in metastatic urothelial carcinoma.

TIGIT’s immuno-oncology teachings

Resolving the mRNA Encapsulation‐Release Trade‐off via Compensatory Forces in Engineered Ionizable Lipids (Adv. Mater. 14/2026)

Stabilizing Iodine Redox Mediator Enables High‐Performance Aqueous Zinc–Sulfur Batteries

ABSTRACT Aqueous zinc–sulfur batteries (AZSBs) are regarded as promising candidates for high‐energy‐density and low‐cost energy storage devices. However, sluggish conversion reaction of sulfur‐loading cathode and notorious polyiodide shuttle of iodine redox mediator in aqueous electrolytes severely hinder the development of AZSBs. Herein, ammonia‐oxidized lignin (AOL) is introduced as electrolyte additive to stabilize the redox mediator function of ZnI 2 , which effectively facilitates the reversible sulfur conversion reaction (S 8 ↔ZnS). As demonstrated, AOL monomer is rich in active hydroxyl/amide moieties, and exhibits strong chemisorption capability for polyiodides as well as remarkable thermodynamic condition for iodine conversion reaction (I 3 − ↔I − ), which significantly blocks the ZnI 2 mediator loss and I 3 − /I 5 − shuttle behavior during cycling, thereby maximizing the catalytic effect of ZnI 2 for S 8 ↔ZnS reaction and high‐performance AZSBs. Consequently, the optimized AZSBs deliver high specific capacity of 1532 mAh g −1 at 0.5 A g −1 , and high reversible capacity of 326.2 mAh g −1 after 320 cycles at 2 A g −1 . Even if assembled into pouch batteries with high sulfur loading of 10 mg cm −2 , high capacity of 514.5 mAh g −1 is still maintained after 134 cycles at 0.5 A g −1 . This work provides novel insights to accelerate sulfur conversion reaction kinetics through stabilizing the redox mediators of AZSBs.

Plant-based dietary indices and quality of life in men with prostate cancer.

356 Background: Prostate cancer is the most prevalent malignancy among US males, with >3.1 million survivors nationally. Treatment-related side effects in the sexual, urinary, bowel, physical, and mental health domains substantially impact quality of life (QOL). Plant-based diets may be associated with better QOL through improved vascular health and anti-inflammatory properties. Methods: This longitudinal cohort study included 1,531 participants with clinically localized (stage T1-T3) prostate cancer managed with primary treatment or active surveillance from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) Diet and Lifestyle sub-study. Participants completed post-diagnosis food frequency questionnaires (FFQ) in 2004-2006. Plant-based diet index (PDI, emphasizing all plant foods regardless of nutritional quality) and healthful plant-based diet index (hPDI, emphasizing nutritionally beneficial plant foods) were calculated based on 18 food groups, with higher scores indicating higher adherence. Serial QOL assessments (median 14 per participant), including the UCLA Prostate Cancer Index for sexual, urinary, and bowel domains, and SF-36 for physical function and mental health, were obtained prospectively over 14.7 years, with a median follow-up of 3.7 years per participant. Participants were censored at the time of additional treatment. Multivariable linear mixed models examined relationships between dietary indices (quintiles) and QOL scores. Primary models adjusted for time from diagnosis to FFQ, time from FFQ to QOL survey, age at diagnosis, CAPRA (Cancer of the Prostate Risk Assessment) score, treatment group, calories, body mass index, smoking status, alcohol, and physical activity. Results: Participants were diagnosed at a median age of 65 years. Higher PDI scores were associated with better sexual function, bowel function, physical function, and mental health, and less sexual bother and bowel bother (all linear p-trend<0.05), with no association for urinary function or bother. The largest relative difference between extreme quintiles of PDI was for sexual function (11% Q5 vs. Q1; 31.6 ± 1.1 vs. 28.4 ± 1.0). Higher hPDI scores were also associated with better bowel function, physical function, and mental health, and less sexual bother and bowel bother (all p-trend<0.05), with a suggestive positive trend for sexual function (p-trend=0.054) and no associations for urinary domains. The largest relative difference between extreme quintiles of hPDI was for physical function (7.4%, Q5 vs Q1: 82.64±0.69 vs. 76.96±0.76). Conclusions: In prostate cancer survivors, eating more plant-based foods after diagnosis was associated with better QOL across multiple domains, especially sexual function. These results are encouraging given the increasing number of survivors living for many years with prostate cancer who often ask if there is anything they can do to improve their QOL.

Safety and efficacy of platinum-based neoadjuvant chemotherapy with gemcitabine at 800 mg/m ² vs. 1000 mg/m ² in muscle-invasive bladder cancer: A multicenter retrospective study.

773 Background: Platinum-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the gold standard treatment for muscle-invasive bladder cancer (MIBC). Gemcitabine plus platinum agents is preferred over MVAC due to similar efficacy and reduced toxicity. However, the optimal gemcitabine dose for balancing safety and efficacy remains unclear. Methods: This multicenter retrospective study included 517 patients with MIBC who received 2–4 cycles of platinum-based NAC with gemcitabine, followed by RC. Patients were divided into two groups based on gemcitabine dosage: the 800 mg/m 2 group and the 1000 mg/m 2 group. The incidence of myelosuppressive hematological adverse events (AEs) was compared between the two groups. Multivariable Cox proportional hazards regression analyses were conducted to assess the impact of gemcitabine dose on cancer-specific survival (CSS) and overall survival (OS). Results: The median age and follow-up duration were 70 years and 55 months, respectively. Of the 517 patients, 348 (67%) received gemcitabine at a dose of 800 mg/m 2 , and 169 (33%) received 1000 mg/m 2 . The rates of grade ≥3 neutropenia and febrile neutropenia did not differ significantly between the 800 mg/m 2 and 1000 mg/m 2 groups (70% vs. 70%, P = 0.958; 4.1% vs. 5.4%, P = 0.523, respectively). However, the incidence of grade ≥3 thrombocytopenia was significantly lower in the 800 mg/m 2 group compared to the 1000 mg/m 2 group (20% vs. 33%, P < 0.001). CSS and OS were significantly shorter in the 800 mg/m 2 group than in the 1000 mg/m 2 group ( P = 0.012 and P < 0.001, respectively). After adjustment for confounding variables, gemcitabine at 800 mg/m 2 was not significantly associated with shorter CSS ( P = 0.471; hazard ratio [HR]: 1.298; 95% confidence interval [CI]: 0.639–2.636) or OS ( P = 0.308; HR: 1.351; 95% CI: 0.758–2.410). Conclusions: Gemcitabine at a dose of 800 mg/m 2 may reduce the incidence of grade ≥3 thrombocytopenia without compromising oncological outcomes. Multivariable analysis for CSS. Factor P value HR 95% CI Age Continuous 0.683 1.006 0.979–1.033 Sex Male 0.738 0.919 0.561–1.506 Performance status Continuous 0.569 1.154 0.705–1.889 Body mass index Continuous 0.853 1.005 0.950–1.065 Cisplatin-based regimens Received 0.215 0.665 0.348–1.268 Tumor grade Grade 3 0.012 2.040 1.170–3.557 Pathological T stage ≥ pT3 0.024 1.805 1.079–3.017 Pathological N stage ≥ pN1 <0.001 2.742 1.663–4.522 Surgical margin Positive 0.086 1.870 0.916–3.816 Urinary diversion Neobladder 0.085 0.665 0.418–1.058 Gemcitabine dose 800 mg/m2 0.471 1.298 0.639–2.636

Predictive capability of combining ExoDx (EPI) and pre-biopsy prostate MRI in detecting clinically significant prostate cancer in African American men.

316 Background: Prostate cancer is the second most common cancer in men and is disproportionately prevalent among African American patients. Several commercially available genomic biomarkers exist to assess the risk of prostate cancer in individual patients; however, studies examining their utility in African American men, especially in combination with prostate MRI, are lacking. This study aimed to evaluate the combined diagnostic and predictive value of pre-biopsy MRI and the ExoDx Prostate (EPI) test for detecting clinically significant prostate cancer (csPCa), defined as Gleason Grade Group 2 or higher, in African American men. Methods: We performed a retrospective analysis of patients who had EPI scores, prostate MRI, and subsequent prostate biopsy at the George Washington Medical Faculty Associates Department of Urology between October 2019 and May 2025, supplemented with clinical data extracted from the Epic EHR. EPI (classified as +EPI ≥ 15.6 and –EPI < 15.6) and MRI data were analyzed across PI-RADS categories (2–5) to assess diagnostic performance metrics, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: A total of 156 patients were included in the analysis. 50 patients were found to have csPCa on prostate biopsy, including 17 (34%) AA patients and 33 (66%) non-AA patients. In the overall cohort, a positive EPI score was associated with a 36.2% risk of csPCa. For all men, AA men, and non-AA men, the risk of csPCa with +EPI and PIRADS 4/5 lesions was 58.1%, 85.7%, and 50%, respectively (AA vs non-AA men p = 0.038). For all men, AA men, and non-AA men, the risk of csPCa with +EPI and PIRADS 3 lesions was 19.3%, 25%, and 17.1%, respectively. For all men, regardless of subgroup, the NPV of -EPI in PIRADS 2/3 lesions was 100%. Conclusions: A positive EPI score significantly increased the risk of csPCa among AA men compared to non-AA men with PIRADS 4/5 lesions. For all subjects with PIRADS 2/3 lesions, a negative EPI had 100% NPV, and may be used as a tool to adjudicate cancer risk in men with equivocal or negative MRIs. These findings support the potential value of the integration of EPI + MRI as a complementary pre-biopsy strategy to enhance risk stratification, equity, and precision in prostate cancer diagnostics. Further validation in larger, prospective, multi-institutional studies is warranted. Baseline demographic and clinical characteristics. Overall (n = 156) AA (n = 46) non-AA (n = 110) Age (avg) 67.4 66.7 67.7 PSA (avg) 6.95 7.75 6.61 PIRADS 2 18 (11.5%) 9 (16.6%) 9 (8.2%) PIRADS 3 67 (42.9%) 20 (43.5%) 47 (42.7%) PIRADS 4/5 71 (45.5%) 17 (37.0%) 54 (49.1%) +EPI ≥ 15.6 130 (83.3%) 36 (78.3%) 94 (85.5%) -EPI < 15.6 26 (16.7%) 10 (21.7%) 16 (14.5%) GG1 36 (23.1%) 8 (17.4%) 28 (25.5%) csPCa (≥ GG2) 50 (32.1%) 17 (37.0%) 33 (30.0%) Negative Biopsy 70 (44.9%) 21 (45.7%) 49 (44.5%)

Approvals by the China NMPA in 2025

Modular Assembly of Lipid Nanoparticles for Targeted mRNA Therapeutics and Vaccines (Adv. Mater. 15/2026)

Exciton Diffusion‐Suppressed Scintillator for Ultrafast and High‐Resolution Radiography

ABSTRACT Organic‐inorganic hybrid scintillator PEA 2 PbBr 4 has emerged as a promising fast scintillator for applications in ultrafast radiation imaging, transient diagnosis of pulsed radiation fields, and medical radiodiagnosis. However, its performance is limited by notably prolonged decay times under high‐energy X‐ray excitation due to inefficient radiative recombination of sparsely distributed bulk excitons. Furthermore, the difficulty in growing and processing high‐quality, large‐area single crystals hinders the development of scalable scintillation screens. Here, we report a general fabrication strategy for large‐area uniform scintillation screens that synergistically enhances the decay time and imaging resolution under X‐ray excitation by suppressing bulk exciton diffusion in PEA 2 PbBr 4 . By leveraging the spatial confinement of nano‐porous templates, we reduce the dimensionality of PEA 2 PbBr 4 from bulk single crystals to uniform 1D nanowires, leading to spatial localization of bulk excitons. This localization significantly shortens the radioluminescence decay time from 11.85 to 1.87 ns. Meanwhile, the regularly aligned periodic optical waveguide structure enables directional propagation of scintillation photons along the nanowires, yielding high spatial resolution imaging (57.1 lp/mm at MTF = 0.2). This work provides a viable approach for advancing the application of organic‐inorganic hybrid scintillators in ultrafast radiation imaging.

Differential quality of life (QoL) with novel hormonal therapy (NHT) in metastatic castration-sensitive prostate cancer (mCSPC): A network meta-analysis of randomized clinical trials.

360 Background: Adding NHT to androgen deprivation therapy (ADT) improves survival in mCSPC, but their comparative impact on patient-reported QoL and time to deterioration (TTD) across FACT-P domains remains underexplored. Methods: MEDLINE and Embase were systematically searched from each database’s inception through August 21, 2025, to identify Phase III trials assessing NHT treatment in mCSPC. Time to FACT-P (total, physical, emotional, functional, and social/family well-being) deterioration across trials with the latest follow up were extracted. Hazards ratios (HRs) and 95% confidence intervals (CIs) were pooled and mixed treatment comparisons were made using network meta-analysis. P-scores were computed; a higher score indicated better QoL. Results: A total of 4 trials (12 references) with 4,037 patients met the inclusion criteria with median follow up ranging from 14.4 months to 30 months. Median time to QoL deterioration ranged from 11.4 to 12.9 months. In terms of FACT-P overall, darolutamide (DARO)+ADT (HR: 0.76; 95% CI: 0.62-0.93), abiraterone acetate (AAP)+ADT (0.85; 0.73-0.98) significantly improved TTD as compared to ADT alone. DARO+ADT was associated with significant improvement in TTD when compared to APA+ADT (0.75; 0.56-0.98). In terms of FACT-P social/family wellbeing, DARO+ADT significantly improved TTD when compared to AAP+ADT (0.75; 0.57-0.96), and ADT (0.79; 0.64-0.98). Likewise, ENZA+ADT significantly improved TTD when compared to AAP+ADT (0.77; 0.63-0.95), APA+ADT (0.88; 0.61-0.99) and ADT (0.82; 0.70-0.95). However, there was no statistically significant difference between DARO+ADT and ENZA+ADT. In terms of FACT-P physical wellbeing, AAP+ADT was associated with statistically significant improvement in TTD when compared to APA+ADT (0.66; 0.52-0.83), ENZA+ADT (0.74; 0.61-0.90), and ADT (0.75; 0.65-0.87). In terms of FACT-P functional wellbeing, DARO+ADT was associated with statistically significant improvement in TTD when compared to ADT (0.78; 0.63-0.96). The ranking analysis is showed in Table. Conclusions: Novel hormonal therapies significantly delay QoL deterioration in mCSPC, particularly across overall, emotional, and functional domains. Domain-specific analyses suggest darolutamide may preserve social/family and functional well-being, while abiraterone favors physical well-being. Rank table. Rank (P-score) FACT-Ptotal FACT-Psocial/family FACT-Pphysical FACT-Pfunctional FACT-Pemotional AAP+ADT 2 (0.73) 5 (0.18) 1 (0.98) 2 (0.62) 3 (0.52) APA+ADT 5 (0.17) 4 (0.22) 5 (0.07) 4 (0.33) 4 (0.52) DARO+ADT 1 (0.90) 1 (0.88) 2 (0.68) 1 (0.92) 2 (0.66) ENZA+ADT 3 (0.50) 2 (0.84) 4 (0.36) 3 (0.52) 1 (0.67) ADT 4 (0.18) 3 (0.38) 3 (0.42) 5 (0.11) 5 (0.13)

IZABRIGHT-Bladder01: A randomized, open-label, phase 2/3 trial of izalontamab brengitecan (iza-bren; BL-B01D1), an EGFR x HER3 bispecific antibody-drug conjugate (ADC), vs platinum-based chemotherapy (PBC) for patients (pts) with advanced urothelial cancer (aUC) and disease progression on or after immunotherapy.

TPS883 Background: While ADC + immunotherapy has been transformative as first-line therapy for aUC, treatment options are limited for pts who progress on or after standard of care immunotherapy-based therapies. Iza-bren is a potentially first-in-class ADC composed of an EGFR x HER3 bispecific antibody, conjugated to a novel topo I inhibitor payload (Ed-04) via a stable tetrapeptide-based cleavable linker. Iza-bren induces tumor cell death via the cytotoxic Ed-04 payload, antibody-dependent cellular cytotoxicity, and inhibition of EGFR and HER3 signaling (both highly expressed in UC). Early-phase study data showed promising antitumor activity and a manageable safety profile in heavily pretreated locally advanced/metastatic tumors, including UC (Ye et al, ESMO 2024). This global, randomized, open-label, phase 2/3 trial evaluates the efficacy and safety of iza-bren vs PBC (gemcitabine + cisplatin or carboplatin) in pts with aUC who progressed on or after anti–PD-(L)1-based therapy. Methods: Key inclusion criteria: adults with histologically/cytologically confirmed advanced transitional cell carcinoma (renal pelvis, ureter, bladder, or urethra), ECOG performance status 0–1, measurable disease per RECIST v1.1, progression or recurrence on or after anti–PD-(L)1-based therapy, and a tumor biopsy collected within 5 years. Pts must be eligible for a PBC regimen with cisplatin or carboplatin and have a ≥ 12-month platinum-free interval. Key exclusions: prior treatment with EGFR and/or HER3-targeted ADCs; topo I inhibitors and/or > 2 prior systemic regimens in any setting. The study comprises 2 parts: phase 2 (dose optimization) and phase 3 (efficacy and safety at recommended phase 3 dose [RP3D]). In phase 2, ~90 pts will be randomized 1:1:1 to iza-bren dose 1 or 2 IV on days 1 and 8 every 3 weeks (D1D8 Q3W) in 21-day cycles, or PBC (cisplatin 70 mg/m 2 IV D1 Q3W or carboplatin AUC 4.5 or 5.0 IV D1 Q3W, + gemcitabine 1000 mg/m 2 D1D8 Q3W for up to 6 cycles). The phase 2 primary endpoint is to determine RP3D (based on safety, efficacy, and PK/PD). Secondary endpoints include objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) (each per RECIST v1.1 by investigator), overall survival (OS), and PK. In phase 3, ~380 pts will be randomized 1:1 to iza-bren at RP3D or PBC. Treatment continues until progression / unacceptable toxicity (PBC limited to 6 cycles). Phase 3 dual primary endpoints are OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints include ORR, DOR (each per RECIST v1.1 by BICR), and time to definitive deterioration (per EORTC QLQ-C30). Further HRQoL is exploratory. Enrollment is ongoing (ClinicalTrials.gov: NCT07106762). Clinical trial information: NCT07106762 .

Phase 1/2 dose escalation/expansion study of REGN10597 (anti–PD-1–IL2Rα-IL2) in patients with advanced solid tumors.

TPS578 Background: Interleukin 2 (IL-2) is a cytokine involved in lymphocyte expansion and differentiation during the anticancer immune response. Despite clinical advances with checkpoint inhibitor therapies, many advanced solid tumors continue to respond poorly to these treatments. Aldesleukin, an approved recombinant high-dose IL-2 therapy, has shown complete and durable responses in some cases; however, high-dose IL-2 is associated with severe toxicity, including vascular leak syndrome and pulmonary edema. REGN10597 is an antibody–cytokine fusion protein comprising a human anti–programmed cell death-1 (PD-1) antibody fused with a receptor-masked cytokine, IL2Rα-IL2. REGN10597 has demonstrated tumor inhibition, enhanced specificity, and reduced toxicity versus recombinant high-dose IL-2 in preclinical mouse models (Wu et al. Cell Rep Med 2024). Here we describe a study evaluating the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of REGN10597 in patients with advanced solid tumors. Methods: This is an open-label, Phase 1/2, dose escalation/expansion, first-in-human, multicenter study evaluating REGN10597 in advanced or metastatic solid tumors (NCT06413680). Patients must be aged 18 years or over with histologically or cytologically confirmed locally advanced or metastatic tumors with confirmed disease progression on standard-of-care therapy. During the dose escalation phase, patients will be enrolled to receive REGN10597 by intravenous infusion at the assigned dose level and schedule (additional dose schedules are available for further exploration). When the recommended Phase 2 dose level and schedule is determined, additional patients will be enrolled across two dose expansion cohorts: patients with locally advanced or metastatic melanoma (Cohort 1) and those with advanced or metastatic clear cell renal cell carcinoma (Cohort 2). Dose escalation primary endpoints include incidence of dose-limiting toxicities, incidence of treatment-emergent adverse events (including those leading to treatment discontinuation or death), incidence of serious adverse events, and the number of patients with Grade ≥3 laboratory abnormalities. The dose expansion primary endpoint is objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment. Secondary endpoints for both phases include additional efficacy measures (best overall response, duration of response, disease control rate, time to response, and progression-free survival, all per RECIST v1.1), and pharmacokinetics and immunogenicity of REGN10597. Trial enrollment for the dose escalation phase began on October 1, 2024; as of October 21, 2025, 18 patients have been enrolled. Clinical trial information: NCT06413680 .