Browse Articles
Discover research articles across all indexed journals
A prospective, randomized, cross-over trial to assess patient preference for goserelin microsphere versus goserelin implant in prostate cancer: Interim results of the GOMIMP study.
130 Background: Androgen deprivation therapy (ADT), particularly gonadotropin-releasing hormone (GnRH) agonists like goserelin, remains a cornerstone in prostate cancer management. While the goserelin implant (Zoladex 3.6 mg) requires subcutaneous administration via a 16G needle (1.6 mm outer diameter) every 28 days, the goserelin microsphere formulation (LY01005 3.6 mg) is administered intramuscularly using a narrower 21G needle (0.8 mm outer diameter) at the same interval. Although phase III data (NCT04563936) confirmed comparable efficacy and safety between these formulations, patient preference remains unexplored. This GOMIMP study evaluates patient preference for the two formulations of goserelin. Methods: In this ongoing crossover trial (NCT06385847), 60 prostate cancer patients are randomized 1:1 to receive either goserelin implant (s.c., 3.6 mg every 28 days for 2 cycles) followed by goserelin microsphere (i.m., 3.6 mg every 28 days for 2 cycles) [Arm 1], or vice versa [Arm 2]. The primary endpoint is patient preference assessed via questionnaire post-treatment. Secondary endpoints include preference rationale, injection tolerability (assessed via Visual Analogue Scale [VAS]), adverse events (AEs), and health-related quality of life (HRQoL). Results: Among 60 enrolled patients, 39 completed both treatment periods and were evaluable. No participants reported “no preference”. Goserelin microsphere was preferred by 35 (89.7%) patients versus 4 (10.3%) patients for the goserelin implant (p=0.0001). After adjusting for period effects via the Prescott test, the preference for goserelin microsphere remained statistically significant (p=0.0017). Patient preference for goserelin microsphere was mainly driven by less injection pain, easier injection, and better quality of life. Preference for goserelin implant was rare and the reasons were inconsistent. Overall, less injection pain (72%) and easier injection (18%) were the two predominant factors influencing patient preference. Goserelin microsphere showed significantly lower immediate injection pain (VAS) compared with goserelin implant (p<0.0001). For injection fear, “marked fear” was observed only at the first injection of goserelin implant (3 patients), whereas most patients receiving microsphere reported “no fear” in Arm 1 (90.5%) and Arm 2 (77.8%). Overall, injection fear was significantly lower for microsphere compared with implant (p<0.0001). In addition, no significant between-arm difference in FACIT-P fatigue, AEs matched known profiles. Conclusions: Interim findings demonstrate a strong patient preference for the goserelin microsphere formulation over the goserelin implant, primarily due to less injection pain and easier injection. Ongoing enrollment will further validate these results.
Correlation of mutated <i>B2M</i> , an immune-related gene, with overall survival in renal cell carcinoma.
555 Background: Renal cell carcinoma (RCC) is the most common renal malignancy and although most cases are sporadic, certain hereditary disorders and genes are associated with its development and response to various immunotherapies. One identified gene implicated in malignant and neoplastic progression and therapeutic resistance is Beta-2-microglobulin (B2M), a component of MHC I class molecules. Our study aimed to explore other gene mutations potentially associated with B2M and any significant findings in survival outcomes with RCC immunotherapy. Methods: NextGen sequencing of DNA (592-gene/whole exome) and RNA (whole transcriptome) was performed on kidney cancer specimens (N = 7104) at Caris Life Sciences (Phoenix, AZ). B2M likely pathogenic/pathogenic (LP/P) mutated patients were used to identify common co-alterations. B2M -high/low expression was defined as > 75 th / < 25 th quartile RNA transcripts per million (TPM). Overall survival (OS) was defined as the time of collection or first of immune checkpoint inhibitor (ICI) to death/last follow-up. Results: Specimens were derived from primary (N = 2950, 41.5%) and metastatic sites (N = 4154, 58.5%) and included all histologies. The most prevalent co-mutations in B2M -mutated tumors include VHL , BAP1 , PBRM1 , NF2 , and SETD2 . Patients with B2M -mutant tumors were found to have worse overall survival, from collection of the specimen to last contact, compared to B2M wild-type tumors (HR = 1.977, 95% CI: 1.47-2.659, P < 0.00001). Additionally, patients with high B2M expression (> 75 th ) had improved survival from start of ICI to last contact compared to patients with low B2M expression (< 25 th ) (HR = 1.34, 95% CI: 1.127-1.593, P < 0.001). BAP1 LP/P mutations were found to be significantly enriched in the high expressors, while B2M LP/P mutations were found to be significantly enriched in the low expressors. While the prevalence of TMB and MSI were not found to be significantly different between the high and low expressors, PD-L1 (SP142) positive frequency (> = 2+ intensity, > = 5% cells stained) was enriched in the higher expressors. Conclusions: Our study demonstrates that Beta-2-microglobulin (B2M) mutation and expression levels, along with numerous other co-mutations, potentially have prognostic and predictive implications in renal cell carcinoma. It remains unclear how these additional genetic mutations interact with each other and with B2M in RCC; however, multiple genes may influence B2M, thereby affecting its expression or the response to treatment. These findings underscore the complex molecular landscape of RCC and highlight B2M and other genetic mutation status as a potential biomarker for predicting therapeutic outcomes and offering new avenues for personalized immunotherapy strategies. Further research may help elucidate the interactions among co-alterations in B2M-mutated RCC and clarify their significance in other cancer types.
TRIM28-mediated SUMOylation of ERG at K389 and its association with cell proliferation, PARP inhibitor response, and 53BP1 expression in castration-resistant prostate cancer.
234 Background: Prostate cancer (PCa) patients with homologous recombination repair (HRR) gene mutations often show sensitivity to PARP inhibitors (PARPis), but this response is inconsistent in HRR-deficient cases. Intrinsic and acquired PARPi resistance remains a major barrier in castration-resistant PCa (CRPC) treatment, highlighting the need to clarify underlying molecular mechanisms. Methods: We first analyzed ERG expression in PARPi-resistant PCa tissues and its correlation with PARPi resistance in CRPC cells. Molecular assays were used to identify TRIM28-mediated ERG SUMOylation and its modification site (K389). The impact of ERG SUMOylation on SPOP-mediated degradation, TP53BP1 transcription, and HRR capacity was evaluated. Finally, small-molecule inhibitor (2-D08) and peptidic inhibitor (ERG K389-peptide) were used to verify the reversal of PARPi resistance by blocking ERG SUMOylation. Results: ERG was highly expressed in PARPi-resistant PCa tissues and positively correlated with CRPC cell resistance. TRIM28 mediated ERG SUMOylation at K389, which inhibited SPOP-dependent ERG degradation to enhance protein stability. This modification also suppressed TP53BP1 transcription, promoting HRR capacity and reducing PARPi sensitivity. Notably, 2-D08 or ERG K389-peptide blocked ERG SUMOylation, impaired DNA repair, and reversed PARPi resistance. Conclusions: TRIM28-mediated ERG K389 SUMOylation is a key axis driving PARPi resistance in CRPC via stabilizing ERG and enhancing HRR. This axis serves as a potential biomarker for resistance prediction and a druggable target, and combining TRIM28/ERG-targeted therapy with PARPis may improve outcomes for ERG-positive CRPC patients.
Corrosion‐Inspired Stabilization of Cobalt Oxide Catalysts via Platinum‐Mediated Redox Buffering for Proton Exchange Membrane Water Electrolysis
ABSTRACT Proton exchange membrane water electrolysis (PEMWE) is considered a promising platform for sustainable hydrogen production at scale. However, the durability of anode catalysts under acidic and oxidative conditions remains a critical challenge. Cobalt‐based oxides offer an attractive alternative to iridium‐based catalysts due to their abundance and cost‐effectiveness, yet suffer from severe chemical and structural degradation during the acidic oxygen evolution reaction (OER). In this study, we report a corrosion‐inspired stabilization strategy based on platinum (Pt)‐mediated redox buffering. Platinum, incorporated within the Co 3 O 4 spinel lattice, functions as a redox‐active buffer, preferentially undergoing oxidation during OER to divert oxidative stress away from the cobalt matrix. In situ X‐ray absorption spectroscopy, inductively coupled plasma‐mass spectrometry analyses, and isotope‐labeled differential electrochemical mass spectrometry collectively demonstrate that Pt incorporation suppresses cobalt dissolution and minimizes lattice oxygen participation, preserving the spinel framework under acidic OER conditions. The resulting Pt‐incorporated Co 3 O 4 catalyst demonstrates outstanding PEMWE performance, achieving a current density exceeding 2500 mA cm −2 at 2.0 V with a turnover frequency of 0.376 s −1 , and maintains stable operation for over 1000 h at 250 mA cm −2 .
High-risk localized prostate cancer treated with neoadjuvant LHRH agonist/antagonist and enzalutamide plus the glucocorticoid receptor antagonist relacorilant versus placebo.
TPS415 Background: Of the estimated 31,000 high risk localized prostate cancer (PC) cases in 2025, up to 46% have a risk of biochemical recurrence after definitive treatment (Falgario U, JAMA Netw Open 2023). A pooled analysis showed 3-year biochemical recurrence-free survival (bRFS) was robustly correlated to pathologic complete response (pCR) plus minimal residual disease (MRD) in patients treated neoadjuvantly (NAJ) with androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) (McKay R, J Urol 2021). A separate study of localized high-risk PC revealed increased glucocorticoid receptor (GR) expression in residual tumors of PC patients (pts) treated with NAJ ARPI plus ADT (Efstathiou E, Eur Urol 2019). Resistance to the ARPI enzalutamide (Enz) is mitigated by targeting GR (Isikbay M, Horm Cancer 2014). We previously demonstrated the safety of the combination of the selective GR antagonist (SGRA) relacorilant (Rel) plus Enz (Desai, CCR , 2024). We have thus initiated a trial to evaluate the NAJ efficacy of this combination. Methods: This phase 2 placebo-controlled 2:1 randomized trial of NAJ LHRH agonist/antagonist and Enz (160 mg daily) plus Rel (150 mg daily)/placebo has a primary objective of response, measured by pCR and MRD at radical prostatectomy (RP). Eligible pts include those with high risk or very high-risk localized prostatic adenocarcinoma per NCCN guidelines, allowing lymph nodes below the iliac bifurcation. After randomization pts will be treated with 6 mo of LHRH agonist/antagonist plus Enz plus Rel/placebo and undergo RP 1 month later. The total sample size is 90 patients with an interim analysis for futility conducted after 45 pts undergo RP. As of October 2025, 30 pts have enrolled, with 23 in follow up and 7 on treatment. A chi-square test will be used to compare the proportion of pts achieving pCR/MRD. Assuming a true CR/MRD rate of 15% in the control group, 90 pts total would yield a power of 80% with a hypothesized CR/MRD of 32% in the Rel group, based on a one-sided test at the alpha=0.15 significance level. Secondary endpoints include evaluating radiographic response within the prostate with multiparametric MRI (mpMRI) and the 3-year bRFS and metastasis-free survival (MFS) rates in both arms. For correlatives, we will demonstrate decreased nuclear hormone receptor-driven proliferative gene expression in viable PC due to NAJ ARPI combined with GR antagonism versus ARPI alone, as well as correlation between pathologic response and enhanced mpMRI imaging. The study is open and seeking additional sites (currently 3 open). ClinicalTrials.gov Identifier: NCT05726292. Clinical trial information: NCT05726292 .
A phase III randomised control clinical trial of radiotherapy with radiosensitisation versus intravesical bacillus Calmette-Guerin therapy for high-risk non-muscle invasive bladder cancer: TRAIN.
TPS880 Background: High-Risk Non-Muscle Invasive Bladder Cancer (HR-NMIBC) is typically treated with surgery (TURBT; Trans Urethral Resection of Bladder Tumour) followed by intravesical BCG (Bacillus Calmette-Geurin), or radical cystectomy. Induction BCG is given weekly for six weeks, followed by maintenance for up to 3 years. However, up to 50% of patients experience recurrence or progression, and 25% discontinue due to toxicity. Global BCG shortages have further increased recurrence rates and costs. There is a clear need for alternative treatments to reduce recurrence, progression, cystectomy rates, and mitigate supply issues. The NIHR funded the TRAIN trial (ISRCTN: 16345179) will assess radiotherapy with radiosensitisation drugs as an alternative treatment option. Methods: Co-ordinated by the Cancer Research UK Southampton Clinical Trials Unit, TRAIN is a multicentre, two arm, open-label UK randomised phase III trial comparing usual care (BCG) with radiotherapy (55Gy/20#) and a radiosensitiser in HR-NMIBC patients who have undergone maximal TURBT and are BCG naïve. Treatment allocation ratio is 1:1, stratified by disease stage and age. Radiotherapy arm participants receive Investigator choice of radiosensitiser (gemcitabine, mitomycin C/fluorouracil or carbogen/nicotinamide) and will receive radiotherapy 55Gy in 20 fractions treating once daily Monday to Friday over 4 weeks. Participants randomised to BCG (control) will be treated following EAU (European Association of Urology) guidelines. All participants will be followed for a minimum of two years. The primary endpoint is event-free survival defined as time from randomisation to any of CIS or high-risk G3 non-muscle invasive papillary tumour recurrence, continued presence of HR-NMIBC even after treatment completion, progression to muscle-invasive disease, distant metastatic bladder cancer, cystectomy (for any reason) or death from any cause. Treatment will continue until the patient has either had an event or unacceptable toxicity or withdrawn. Accounting for 5% drop out, the total sample size of 328 patients (90 events) was calculated using alpha = 0.025 (one-sided), power = 0.9, hazard ratio = 0.5, and a piecewise exponential survival distribution with event rate in the control arm of 10, 20, 25 and 30% at 3, 6, 12 and 24 months. An interim analysis for futility is planned for when 50% of events have occurred. The study will stop if the observed hazard ratio is greater than 0.924. Secondary endpoints include recurrence-free survival, cancer specific survival, cystectomy-free survival, progression-free survival, metastasis-free survival, overall survival, treatment fidelity, cost-effectiveness and safety/tolerability. TRAIN will be run in approximately 12-20 UK secondary care hospitals. Clinical trial information: 16345179.
Impact of bleomycin shortage on real-world outcomes in germ cell tumors: A multicenter retrospective analysis in Brazil.
600 Background: Male germ cell tumors are rare malignancies, accounting for approximately 5% of all male cancers and predominantly affecting young adults. Most originate in the testis and are classified as seminomatous or non-seminomatous. Depending on clinical stage, different polychemotherapy regimens may be indicated, with or without bleomycin. Since 2017, Brazil—like several other countries—has faced recurrent shortages of bleomycin due to reduced global production, limited raw material availability, regulatory and logistical import barriers, and low commercial incentives for manufacturing this low-cost drug. In this context, this study aimed to evaluate the clinical impact of bleomycin unavailability on treatment outcomes in patients with germ cell tumors. Methods: A retrospective study was conducted including patients with germ cell tumors treated from 2017 to 2024 in two large public oncology centers in Brazil. Outcomes were compared between patients receiving bleomycin-containing regimens (BEP: bleomycin, etoposide, and cisplatin) and alternative regimens without bleomycin (EP: etoposide and cisplatin; VIP: etoposide, ifosfamide, and cisplatin). Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method, and factors associated with treatment type were evaluated through multivariate logistic regression. Additionally, hospitalization rates, treatment delays, and chemotherapy-related toxicities were assessed and compared between groups. Results: A total of 179 patients with germ cell tumors were evaluated. Among them, 57 received BEP, 36 received EP, and 13 received VIP. The comparative analysis of survival and treatment outcomes was performed between the BEP group and the combined non-bleomycin group (EP/VIP). There was no statistically significant difference in OS (p=0.593) or DFS (p=0.480) in the comparison of these 2 groups. Hospitalization rates (40.8% vs. 31.6%; p=0.323) and overall toxicity profiles were similar. However, patients treated without bleomycin presented a higher frequency of non-infectious hematologic toxicities (25.9% vs. 14.3%), which may have contributed to the significantly higher rate of treatment delays (59.2% vs. 33.3%; p=0.008). These adverse events generally did not require hospitalization but led to temporary chemotherapy postponements to allow hematologic recovery. Conclusions: Replacing bleomycin with alternative regimens (EP/VIP) did not compromise survival outcomes and showed comparable hospitalization and overall toxicity rates, although a higher rate of treatment delays was observed, likely due to increased mild or moderate hematologic toxicities. These real-world data support the feasibility of non-bleomycin regimens in contexts of drug shortage and contribute to evidence-based clinical decisions in germ cell tumor management.
A phase 1/2 study to assess peptidomimetic carbonic anhydrase IX imaging and therapy with [ <sup>68</sup> Ga]Ga-DPI-4452 and [ <sup>177</sup> Lu]Lu-DPI-4452 in patients with advanced clear cell renal cell carcinoma and other solid tumors.
TPS569 Background: The diagnostic and clinical benefit of the peptidomimetic carbonic anhydrase IX (CA IX) -binding theranostic pair [ 68 Ga]Ga-DPI-4452/[ 177 Lu]Lu-DPI-4452 is being investigated in an ongoing, multicenter, Phase 1/2 study (NCT05706129). The study design comprises 5 parts; First-in-Human Part A assessed safety, pharmacokinetics, biodistribution and dosimetry of a single intravenous injection of 185 MBq [ 68 Ga]Ga-DPI-4452 in various solid tumors including clear cell renal cell carcinoma (ccRCC), and has been completed (Hofman et al, 2024). Theranostic Parts B and C will determine one or more recommended Phase 2 dose(s) (RP2D) and evaluate preliminary antitumor activity of [ 177 Lu]Lu-DPI-4452 in patients with advanced ccRCC, and potentially in other tumor types. Major objectives of the additional imaging Parts D and E are to evaluate the diagnostic concordance between [ 68 Ga]Ga-DPI-4452 PET and histopathology in patients with indeterminate renal mass (IDRM) (Part D) and to explore [ 68 Ga]Ga-DPI-4452 uptake in different tumor types (Part E). Methods: In the Phase 1 dose escalation (Part B), patients with ccRCC are currently enrolled and undergo [ 68 Ga]Ga-DPI-4452 imaging as part of screening to confirm and quantify tumor CA IX expression, i.e., eligibility for [ 177 Lu]Lu-DPI-4452 therapy. Optional [ 68 Ga]Ga-DPI-4452 PET scans may be conducted during treatment alongside conventional tumor assessments. Approximately 64 evaluable patients with ccRCC and potentially other tumor types will be included to establish the maximum tolerated dose and/or one or more RP2D for each tumor type. Subsequently, the preliminary antitumor activity of [ 177 Lu]Lu-DPI-4452 monotherapy at RP2D will be evaluated in tumor-specific Phase 2 expansion cohorts (Part C). Part D is open for recruitment with the goal to include approximately 36 patients with IDRM. Patients receive a single dose of [ 68 Ga]Ga-DPI-4452 at 185 MBq (±20%) followed by whole body PET/CT scans at 1 and 3 hours post-infusion. Confirmation of tumor lesions as ccRCC is based on mean and maximum standard uptake values. Tumor tissue samples are collected during radical or partial nephrectomy, biopsy or other invasive diagnostic methods as per local standard practice within 90 days. Clinical trial information: NCT05706129 .
Stabilizing Ni <sup>3+</sup> ‐Rich NiO <sub>x</sub> /Perovskite Interface via Dual Coordination for Efficient and Durable Perovskite Photovoltaics
ABSTRACT While nickel oxide (NiO x ) is widely employed as an efficient hole‐transport material, the surface Ni 3+ species required for effective transport are unstable and can drive unfavorable interfacial reactions with the perovskite layer. Herein, we introduce a tetraoxopyridine‐functionalized porphyrin molecule to stabilize a Ni 3+ ‐rich NiO x /perovskite interface through dual coordination. Two oxopyridines in porphyrin act as hard Lewis bases that coordinate with hard‐acidic Ni 3+ sites on NiO x , while the other two interact with Pb 2+ in the perovskite lattice. Such a situation reduces interface defect formation, slows degradation, and helps maintain film integrity, while the conjugated porphyrin macrocycle promotes efficient hole extraction. Devices with the modified NiO x reach the champion efficiency of 27.05% (0.062 cm 2 ) and 21.8% (21.54 cm 2 aperture area), retaining >95% of the initial efficiency after 2000 h of continuous 1‐sun operation at the maximum power point. This work establishes a robust molecular‐engineering route to stabilize surface Ni 3+ in NiO x and support high‐efficiency, long‐lived perovskite solar cells.
The prognostic role of PD-L1 in penile squamous cell carcinoma: A systematic review and meta-analysis.
13 Background: Penile squamous cell carcinoma (PSCC) is a rare tumor with limited therapeutic options in advanced disease. Given the role of PD-L1 as a prognostic biomarker in many cancer subtypes, assessing its value in PSCC may inform prognosis and guide the use of immune checkpoint inhibitors in metastatic disease. In this systematic review and meta-analysis, we evaluate the prevalence of PD-L1 tumor expression in PSCC and assess its prognostic association with overall survival (OS), cancer-specific survival (CSS), and lymph node metastasis (LNM). Methods: We searched PubMed, Embase and Cochrane for relevant studies. The primary outcomes were OS, CSS, and LNM, analyzed using HRs or ORs, each with 95% CIs. Outcomes were prespecified in the PROSPERO protocol (CRD42019129410). Random-effects meta-analyses (restricted maximum-likelihood estimator) were performed using inverse-variance weighting. Heterogeneity was assessed by Q, τ², and I² statistics. Publication bias was examined by Egger’s test and funnel plots. Results: Fifteen retrospective studies were included (N = 1,445). Overall, 57% of tumors were PD-L1 positive (IQR, 44%–66%). Among 796 patients, PD-L1 expression was significantly higher in HPV-negative than in HPV-positive tumors (42% vs 13.5%). Eight studies (N = 930) evaluated OS, nine studies (N = 1,091) assessed CSS, and five studies (N = 622) investigated LNM. PD-L1 positivity was associated with reduced OS (HR 1.52; 1.12–2.05; I² = 6.8%) and CSS (HR 1.61; 1.16–2.23; I² = 38.3%), and with higher odds of LNM (OR 2.94; 1.28–6.78; I² = 57.3%). In meta-regression, HPV adjustment significantly strengthened CSS associations (QM = 7.13, p = 0.008; HR = 2.06, 1.21–3.51), accounting for all observed heterogeneity. Other moderators (sample size, adjustment status, tumor stage, study location, tumor-cell vs TIL scoring) were non-significant. Conclusions: PD-L1 expression is more frequent in HPV-negative PSCC and is consistently associated with adverse clinical outcomes, including shorter OS, shorter CSS, and higher odds of LNM. These findings support PD-L1 as a potential prognostic biomarker in PSCC and underscore the importance of considering HPV status in prognostic and therapeutic stratification.
The LuxAR-02 phase II study of luxdegalutamide in combination with [ <sup>177</sup> Lu]Lu-PSMA-617 in patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration resistant prostate cancer (mCRPC).
TPS278 Background: Patients with mCRPC have a poor prognosis and often experience rapid disease progression with current standard therapies. Treatment resistance in mCRPC is frequently driven by the reactivation of androgen receptor (AR) signaling pathways, despite castration or AR-targeted therapies. Luxdegalutamide is a potent oral proteolysis targeting chimera (PROTAC) AR degrader. In a phase I/II study, luxdegalutamide was well tolerated and showed encouraging antitumor activity in heavily pretreated patients with mCRPC (NCT05067140). Preclinically, luxdegalutamide shows additive activity when combined with 177 Lu-PSMA-617 in vivo in prostate cancer models, an effect that may be driven by prostate-specific membrane antigen (PSMA) upregulation. This phase II randomized, open-label, multi-center study aims to evaluate the efficacy, safety, and tolerability of two oral daily dose regimens of luxdegalutamide in combination with 177 Lu-PSMA-617 compared to 177 Lu-PSMA-617 alone in patients with PSMA-positive mCRPC (NCT07047118). Methods: Approximately 130 adult male patients with PSMA-positive (meeting criteria used in VISION trial) mCRPC and prior exposure to at least 1 androgen receptor pathway inhibitor and up to two taxanes will be randomized in a 5:5:3 ratio to one of the 3 arms: Arm 1: Luxdegalutamide 100 mg QD + 177 Lu-PSMA-617 (7.4 GBq q6 weeks). Arm 2: Luxdegalutamide 300 mg QD + 177 Lu-PSMA-617 (7.4 GBq q6 weeks). Arm 3 (control): 177 Lu-PSMA-617 (7.4 GBq q6 weeks). Randomization will be stratified by prior taxane (yes vs. no), and visceral metastases (yes vs. no). The primary objectives are to identify the recommended phase III dose of the combination based on efficacy (PSA50 response rate), safety, tolerability and PK data, and to compare the efficacy in arms 1 and 2 versus control. As of 07 October 2025, 15 patients have been enrolled. Clinical trial information: NCT07047118 .
Real-world ARPI utilization patterns and outcomes in metastatic castration-sensitive prostate cancer.
119 Background: Intensification of androgen deprivation therapy (ADT) with androgen receptor pathway inhibitors (ARPIs) or taxanes is the standard of care for treating metastatic castration-sensitive prostate cancer (mCSPC). This study evaluated the real-world (RW) adoption of ADT intensification regimens and assessed outcomes in mCSPC patients (pts). Methods: A US-based deidentified RW database (Integra PrecisionQ) was used to identify mCSPC pts who initiated first-line (1L) therapy between 1-Jan-2020 and 31-Mar-2025. 1L treatment regimens and proportion of regimens that included an ARPI were analyzed by year (2020-2025). Baseline pt characteristics included age, payer type, region, and comorbidities. We compared time to next treatment (TTNT) and time to discontinuation (TTD) between ARPI-intensified ADT combinations and ADT monotherapy (mono), including the individual performance of each ARPI. TTNT was defined as the time from initiation of the 1L treatment to the start of subsequent treatment and TTD was defined as the time from initiation of 1L treatment to its discontinuation. Results: A total of 2300 pts received 1L treatment for mCSPC between 2020 and 2025, with a cohort median follow-up of 15 months after initiating IL treatments. Of 2300 pts, 1739 (74.6%) received ADT intensification and 1420 of 1739 (82%) received ADT intensification with ARPI. Use of ARPI combinations increased from 55.3% (198/358) in 2020 to 67.1% (349/520) in 2024. Use of the ARPI + docetaxel + ADT triplet increased from 0.8% (3/358) of total regimens in 2020 to 7.5% (39/520) in 2024. Median TTNT for ARPI-intensified doublet regimens compared to ADT mono is summarized in the table (n=1652: ADT mono, n=591 vs. ADT + any ARPI, n=1061). There were no large differences in median TTNT for each ARPI doublet. After adjusting for age at treatment, race, payer mix, and comorbidities, pts receiving ARPI doublet regimens were significantly more likely to stay on therapy compared to those on ADT mono (HR 0.79; 95% CI: 0.69, 0.91). Conclusions: In a large deidentified RW database mCSPC ADT-ARPI intensification is increasingly used. Irrespective of the type of ARPI intensification received, pts treated with ADT + ARPI stayed on therapy significantly longer than pts treated with ADT monotherapy. Despite the observed benefit with ARPI intensification, one-quarter of pts received ADT monotherapy. Median TTNT and TTD of selected 1L mCSPC regimens (N=1652 of 2300).* Regimen ADT Mono (n=591) ADT + any ARPI (n=1061) ADT + AA/P(n=379) ADT + Enzalutamide(n=412) ADT + Apalutamide(n=186) ADT + Darolutamide (n=84) Age at 1L treatment (yr) 70.2 70.8 70.4 70.3 70.2 70.1 Median TTD (mo) 12.1 19.5 19.1 18.9 21.3 24.1 Median TTNT (mo) 13.4 20.5 20.5 19.6 22.1 24.4 AA/P, abiraterone acetate/prednisone. *Other therapies (n=648) including ADT + docetaxel and ADT + docetaxel + ARPI were not part of the primary comparison and are not included in this table.
Direct comparative and network meta analysis of PARP inhibitor and androgen receptor targeted therapies in first line mCRPC: Defining the optimal regimen among 8,997 patients.
201 Background: Metastatic castration resistant prostate cancer remains a lethal stage despite major therapeutic advances. The introduction of androgen receptor targeted agents and PARP inhibitors has redefined first line management. However, the optimal regimen and relative efficacy among available therapies remain uncertain, as pivotal trials were conducted in distinct populations and lacked direct comparative data. Methods: A Bayesian network meta analysis was performed using data from four phase III randomized trials: PROpel, COU AA 302, ACIS, and PREVAIL, including 8997 patients. Hazard ratios for radiographic progression free survival and overall survival were extracted. Relative treatment effects were estimated using a Bayesian hierarchical model integrating direct and indirect head to head comparisons. Surface Under the Cumulative Ranking (SUCRA) probabilities were derived to rank each regimen by likelihood of being most effective. Results: Among 8997 patients from four phase III trials, Olaparib plus Abiraterone ranked highest for progression free survival, while Abiraterone showed the greatest overall survival probability. Enzalutamide provided consistent efficacy across both endpoints. SUCRA based ranking as mentioned in the table 1 showed clear separation between treatment and control arms. Conclusions: This network meta analysis defines the first unified hierarchy of first line regimens for metastatic castration resistant prostate cancer, integrating nearly nine thousand patients from pivotal trials. Olaparib plus Abiraterone achieved the greatest delay in progression, reinforcing the synergistic potential of PARP inhibition with androgen receptor blockade. Abiraterone showed the highest overall survival probability, confirming its position as the most validated survival benchmark, while Enzalutamide maintained consistent efficacy across both endpoints. Overall survival data for PARP inhibitor combinations remain premature but suggest meaningful benefit with longer follow up. These findings define a clear evidence based hierarchy of efficacy, guiding regimen selection when toxicity, cost, or access limit preferred agents, and highlight the evolution of mCRPC therapy toward mechanism driven combinations that extend survival and quality of life. Rank Treatment SUCRA (95% CrI) rPFS SUCRA (95% CrI) OS 1 Olaparib + Abiraterone + Prednisone 92 (85–98) 82 (70–93) 2 Abiraterone + Prednisone 78 (65–89) 85 (75–94) 3 Enzalutamide 65 (52–78) 80 (68–91) 4 Apalutamide + Abiraterone 45 (32–58) 38 (25–51) 5–6 Placebo ± Prednisone 15 (5–25) / 5 (1–12) ≤ 15 Ranking based on Bayesion head to head analysis and SUCRA scores of rPFS (radiological progression free interval) and OS (overall survival).
Efficient Direct Recycling Strategy of Spent LiFePO <sub>4</sub> Cathodes by Structural Defect Repair and Interface Construction
ABSTRACT The increasing number of retired LiFePO 4 batteries urgently requires efficient and environmentally friendly recycling methods. The primary causes of LiFePO 4 battery failure can be attributed to lithium loss and the formation of Fe(III) phases. Therefore, the synergistic interaction between the green reagent citric acid (CA) and urea (UR) achieves low‐temperature spontaneous defect repair and the construction of an N‐doped carbon layer. Specifically, CA creates a reductive atmosphere that reduces Fe(III) to the Fe(II) phase, thereby eliminating Li‐Fe anti‐site defects. Meanwhile, the amino group (─NH 2 ) in UR acts as a nitrogen source, enabling N‐doping modification of the carbon layer on the surface of LiFePO 4 particles. The formed N‐doped carbon layer effectively improves the electronic conductivity and lithium‐ion migration dynamics of regenerated LiFePO 4 (R‐LFP). Moreover, the strengthening of Fe‐O and P─O bonds further increases the overall structural stability of R‐LFP, resulting in its remarkable electrochemical performance. The R‐LFP electrode material delivers 163 mAh/g specific capacity during the first discharge cycle at 0.1C and retains 93.5% of its initial capacity after 500 cycles at 1C. This economical and environmentally friendly recycling strategy provides a greatly promising solution for the sustainable recovery of lithium‐ion batteries (LIBs).
Treatment interruption guided by on-treatment prostate-specific membrane antigen (PSMA) PET/CT imaging in metastatic hormone-sensitive prostate cancer (mHSPC).
22 Background: PSMA PET/CT (PET) imaging is approved for staging high-risk prostate cancer (PCa) and for suspected PCa recurrence based on elevated PSA levels, but is not validated for clinical decision making in patients (pts) responding to treatment. We investigated clinical management and outcomes of pts with mHSPC who underwent on-treatment PET at our institution. Methods: The Dana-Farber/Harvard Cancer Center (DF/HCC) Oncology Data Retrieval System (OncDRS) was queried for pts with mHSPC (by PET or conventional imaging) who underwent PET 3-24 months after starting androgen deprivation therapy (ADT) plus an AR pathway inhibitor (ARPI). Pts with castration-resistant PCa (CRPC), non-metastatic PCa, without a PET in this window, and those treated with ADT alone were excluded. Pts were categorized as having no active disease on PET (group 1), uptake only in sites previously treated with radiation therapy (RT) (group 2) or uptake in sites not previously treated with RT (group 3) based on the 1st on-treatment PET. RT to local or distant site(s) post-PET, and treatment interruption / resumption were descriptively tabulated. Time to development of CRPC was analyzed by group using landmark analysis. Results: The OncDRS query returned 596 pts, 68 meeting eligibility criteria. 19 were categorized into group 1, 13 in group 2 and 36 in group 3. 14 pts underwent RT after PET. 28 of 32 pts in groups 1+2 eventually interrupted systemic therapy (of whom 2 of 28 had received post-PET RT) compared to 18 of 36 in group 3 (of whom 8 of 18 had received post-PET RT). At median follow up of 35.3 months from ADT start, 11 of 68 pts developed CRPC and 3 of 68 pts died; 30 of 46 pts who interrupted treatment remained off hormonal therapy (Table). Conclusions: A majority of pts with mHSPC at our institution who underwent on-treatment PSMA PET 3-24 months after starting ADT+ARPI (without evidence of CRPC) eventually interrupted systemic therapy, a subset of whom underwent post-PET RT prior to interruption. Given the favorable clinical outcomes observed in these responding pts, the utility of on-treatment PSMA PET in mHSPC warrants prospective investigation in larger cohorts. DF/HCC protocol 24-620. Clinical outcomes by PET response. PET response Group 1 (N=19) Group 2 (N=13) Group 3 (N=36) PSA detectable at 1 st on treatment PET, N (%) (min-max) 1 (5.3%)(<0.02, 0.04) 6 (46.2%)(<0.02, 1.10) 18 (50.0%)(<0.02, 4.45) Median (range) time from treatment start to PET, mo 12.0 (5.6, 24.3) 9.2 (6.5, 25.1) 9.0 (3.8, 23.8) Median (range) follow-up post PET, mo 16.7 (2.9, 35.5) 27.6 (8.8, 44.3) 25.7 (14,4, 45.3) Post-PET RT 1 1 12 Treatment interruption / resumption 16 / 3 12 / 7 18 / 6 Treatment resumption rate at 12 mo after interruption 27.0%(9.1%, 64.7%) 39.4%(16.6%, 74.9%) 15.4%(4.1%, 48.8%) CRPC events 3 1 7 CRPC-free rate at 2-years from PET (landmark) 78.8% (38.1%, 94.3%) 100% 81.0% (62.0%, 91.1%) Deaths 0 1 2
Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: Randomized, open-label, phase 3 KEYNOTE-B15 study.
LBA630 Background: Enfortumab vedotin (EV) + pembrolizumab (pembro) is the established first-line standard of care for locally advanced/metastatic urothelial carcinoma and represents a novel neoadjuvant and adjuvant treatment strategy for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy. The randomized phase 3 KEYNOTE-B15/EV-304 study (NCT04700124) evaluates neoadjuvant and adjuvant EV + pembro followed by radical cystectomy plus pelvic lymph node dissection (RC + PLND) vs neoadjuvant chemotherapy followed by RC + PLND in participants (pts) with MIBC who are eligible for cisplatin-based therapy. Methods: Pts with clinical stage T2-T4aN0M0 or T1-T4aN1M0 MIBC (confirmed by central pathology and central imaging assessment) who were eligible for cisplatin-based chemotherapy and RC + PLND were randomized 1:1 to receive either 4 cycles neoadjuvant EV 1.25 mg/kg IV on days 1 and 8 + pembro 200 mg IV on day 1 Q3W, followed by RC + PLND, and adjuvant 5 cycles EV + 13 cycles pembro (EV + pembro arm) vs 4 cycles neoadjuvant gemcitabine 1000 mg/m 2 on days 1 and 8 + cisplatin 70 mg/m 2 on day 1 Q3W, followed by RC + PLND (cis + gem arm). The primary endpoint was event-free survival (EFS) by blinded independent central review. Key secondary endpoints were pathological complete response (pCR) rate by blinded central pathological review and overall survival (OS). Safety was a secondary endpoint; AEs of special interest were based on distinct prespecified lists for each drug. Results: A total of 405 and 403 pts were randomized to EV + pembro and cis + gem, respectively. Median time from randomization to the data cutoff date of October 27, 2025 was 33.6 months (range, 22.5–53.6). Baseline characteristics were generally balanced between groups. EV + pembro significantly improved EFS (median NR vs 48.5 mo; 24-mo estimated EFS rate 79.4% vs 66.2%; HR 0.53, 95% CI 0.41–0.70; 1-sided P <.0001), OS (median NR vs NR; 24-mo estimated OS rate 86.9% vs 81.3%; HR 0.65, 95% CI 0.48–0.89; 1-sided P =.0029), and pCR rate (55.8% vs 32.5%; estimated difference 23.4%, 95% CI 16.7–29.8; 1-sided P <.0001) vs cis + gem. Grade ≥3 treatment-emergent AEs occurred in 75.7% of pts with EV + pembro and 67.2% with cis + gem. Most common grade ≥3 drug-related AE of special interest for EV was skin reactions (14.1%); most common grade ≥3 AE of special interest for pembro was severe skin reactions (13.9%). Conclusions: Neoadjuvant and adjuvant EV + pembro significantly improved EFS, OS, and pCR rate compared with neoadjuvant gem + cis in pts with MIBC who were eligible for cisplatin-based chemotherapy. The safety profile of EV + pembro was consistent with prior experience with the combination. These results support EV + pembro as an effective perioperative treatment option in this setting. Clinical trial information: NCT04700124 .
Real-world effectiveness of systemic therapies after [ <sup>177</sup> Lu]Lu-PSMA-617 ( <sup>177</sup> Lu-PSMA-617) treatment in patients with metastatic castration-resistant prostate cancer (mCRPC): A prostate cancer disease observation (PRECISION) data platform analysis.
79 Background: In March 2025, the indication for 177 Lu-PSMA-617 was expanded to include prostate-specific membrane antigen (PSMA)-positive patients with mCRPC treated with ≥1 androgen receptor pathway inhibitor (ARPI) and considered appropriate to delay taxane-based chemotherapy. With 177 Lu-PSMA-617 moving earlier in the treatment journey, it is important to understand the clinical activity of other systemic therapies after 177 Lu-PSMA-617. The aim of this study was to evaluate the clinical outcomes among patients with mCRPC receiving a systemic therapy after 177 Lu-PSMA-617 treatment. Methods: This retrospective, observational study used real-world data from the PRECISION data platform, a proprietary dataset developed by Novartis representative of patients with advanced prostate cancer in the US from diverse clinical settings. Patients with mCRPC treated with 177 Lu-PSMA-617 who received a systemic therapy ≥14 days after treatment with 177 Lu-PSMA-617 between March 23, 2022, and June 27, 2025, were included. Systemic therapies included ARPIs (abiraterone, enzalutamide, darolutamide, apalutamide); chemotherapy (cabazitaxel, docetaxel, carboplatin, cisplatin, etoposide, mitoxantrone); immunotherapy (pembrolizumab, sipuleucel-T); poly (ADP-ribose) polymerase (PARP) inhibitors (niraparib, olaparib, talazoparib, rucaparib); and radium-223. Patient characteristics and prostate-specific antigen (PSA) response were evaluated descriptively. Progression-free survival (PFS) from subsequent therapy initiation was estimated using Kaplan–Meier methodology. Results: A total of 442 patients receiving any subsequent systemic therapy after 177 Lu-PSMA-617 were included. Overall, 95% of patients received ≥1 ARPI and 76% ≥1 taxane pre- 177 Lu-PSMA-617. The median age was 73 years. Most patients received a taxane (n = 188), an ARPI (n = 176), or a PARP inhibitor (n = 33) as their subsequent therapy. The median time to subsequent therapy initiation was 70 days (interquartile range 38−137 days) from the last 177 Lu-PSMA-617 administration. Among 299 patients receiving a systemic therapy after 177 Lu-PSMA-617 with PSA values available both pre-index and during subsequent treatment, 48% achieved a ≥50% reduction in PSA from baseline (PSA50), 31% a PSA80, and 18% a PSA90. The median PFS from the initiation of subsequent therapy was 8.6 months in the entire cohort; this was 10.7 months with a subsequent ARPI, 7.2 months with a subsequent taxane, and 7.1 months with a subsequent PARP inhibitor. Conclusions: In this real-world analysis, meaningful clinical responses were observed in a subset of patients who received subsequent systemic therapies after 177 Lu-PSMA-617.
Sarcomatoid versus rhabdoid dedifferentiation and histologic grade-specific outcomes in metastatic clear cell renal cell carcinoma (mccRCC): A multi-institutional analysis of 514 patients.
456 Background: WHO/ISUP grade 4 RCC, defined by rhabdoid or sarcomatoid dedifferentiation or extreme nuclear pleomorphism, is associated with aggressive biology and poor outcomes. While sarcomatoid dedifferentiation is recognized as a particularly adverse prognostic phenotype, the clinical impact of individual grade patterns remains uncertain. Using a large multi-institutional dataset, we examined clinical outcomes according to histologic grade and dedifferentiation status. Methods: Patients with mccRCC treated with first-line nivolumab and ipilimumab were retrospectively identified. Patients were categorized based on tumor ISUP grade and dedifferentiation status: sarcomatoid, rhabdoid, both sarcomatoid and rhabdoid (S+R), ISUP grade 4 without sarcomatoid or rhabdoid (Gr4nonS/R) and ISUP Grade ≤3. Disease characteristics, time to next treatment (TTNT) and overall survival (OS) were compared between each ISUP Grade 4 category and ISUP Grade ≤3. Multivariable models adjusting for IMDC risk, number of metastatic sites, and nephrectomy status assessed the independent effects of sarcomatoid and rhabdoid dedifferentiation. Results: Among 514 patients, 197 had ISUP Gr≤3 disease, 179 had grade 4 disease (61 with sarcomatoid, 67 with rhabdoid, 51 with S+R, 35 with gr4nonS/R), while 103 had ccRCC but not evaluable histological grade. Patient characteristics were comparable across cohorts, except for higher IMDC risk, and a greater frequency of de-novo metastatic disease in sarcomatoid (p = 0.004 and p = 0.01, respectively), a higher proportion of females in rhabdoid (p = 0.01), and more de-novo metastatic disease in S+R (p = 0.009), compared with the Gr≤3 reference group. While TTNT was comparable across histologic grade groups, pairwise analyses for OS using ISUP Gr ≤3 (5.4 yrs [95%CI 4.5, 7.7]) as reference, yielded worse median OS in sarcomatoid (2.9 yrs [95% CI 2.0, 3.8], p = 0.01), but not other grade 4 categories: R (Not reached [NR], [95% CI 3.2, NR], p = 0.84), S+R (9.1 yrs [95% CI 1.9, 9.1] p = 0.12), or Gr4nonS/R (6.5 yrs [95% CI 2.9, NR], p = 0.86). In multivariable analyses, sarcomatoid (Yes/No) was independently associated with worse OS (HR 1.56, 95% CI: 1.13, 2.16; p = 0.007), whereas rhabdoid features (Yes.no) showed no such association (HR: 0.97, 95% CI: 0.68, 1.37; p = 0.84). Conclusions: Sarcomatoid dedifferentiation was independently associated with worse OS, whereas rhabdoid features did not show a comparable adverse effect in mccRCC treated with first line nivolumab/ipilimumab. Findings reinforce the prognostic weight of sarcomatoid dedifferentiation despite treatment with nivolumab/ipilimumab and suggest a less aggressive phenotype and a female predilection for rhabdoid differentiation, which requires further clinical and translational investigation.
Fifteen-year survival analysis from the ASCENDE-RT randomized trial of external beam boost versus brachytherapy boost in localized prostate cancer.
306 Background: Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) trial randomized patients to prostate brachytherapy (PB) or the External beam RT (EBRT) boost (1:1). All patients received 1 year of androgen deprivation therapy and 46 Gy in 23 fractions of pelvic RT. Patients in the EBRT arm received an additional 32 Gy in 16 fractions, and those in the PB arm received a 115 Gy 125I implant. The trial previously demonstrated a large difference in biochemical relapse favoring brachytherapy (PB) boost. At present, the median follow-up from start of treatment of all patients is 15 (IQR 10.7, 17.8) years. Herein we report the 15-year actuarial survival events. Methods: Two hundred patients with a median age of 68 (IQR 62,73) were randomized to EBRT and 198 to PB. Active study follow-up stopped at 10 years. Cause of death was determined on chart review and study report forms during active study follow-up, and was augmented with death registry data, and medical records audits thereafter. Fifteen-year overall survival and cumulative risk of death from prostate cancer were estimated using Cox and Fine and Gray analysis respectively with multivariable analysis (MVA) significant variables on univariate including - randomization, clinical T stage, log of initial PSA, Gleason grade group (1-3 vs 4-5), percent positive cores, and age at treatment. A sensitivity analysis included unknown cause of death as prostate death. Results: 213 patients (54%) have died: 64 (16%) of prostate cancer, 48 (12%) of other cancer, 35 (9%) of cardiovascular disease, 49 (12%) of other known causes, and 17 (4%) of unknown cause of death. The age of patients alive at last censoring was 82 (IQR 77,88). Overall survival at 15 years was 55.0% (95% CI 48.4 – 62.4) and 60.9% (95% CI 54.4 – 68.1) for EBRT and PB arms respectively, (HR 1.02, 95%CI 0.78 – 1.33, p = 0.908 on MVA). The cumulative incidence of prostate death at 15 years was 8.6% (95%CI 5.2 – 13.0) for PB and 16.4% (95%CI 11.6 – 22.0) for EBRT (p=0.007). In a sensitivity analysis where cases of unknown cause of death were counted as prostate deaths, the cumulative incidence of prostate death at 15 years was 14.3% (95%CI 9.8 – 19.5) for PB and 19.4% (95%CI 14.2 – 25.3) for EBRT (p=0.067). Conclusions: At 15 years, there is no definite evidence of an overall survival benefit with PB boost in ASCENDE-RT and the trend to a prostate cancer specific survival advantage with PB is limited by ascertainment of cause of death. Thus, although prostate cancer was the single most common cause of mortality in ASCENDE-RT, our results suggest that even large improvements in b-NED, such as those demonstrated with PB in ASCENDE-RT, are unlikely to improve 15-year overall survival by more than 10% for a population whose median age, performance status, and prognostic variables are similar to ASCENDE-RT participants. Clinical trial information: NCT00175396 .
Avelumab (Ave) in combination with other anticancer agents as first-line maintenance (1LM) treatment for advanced urothelial carcinoma (aUC): Primary analysis from the JAVELIN Bladder Medley phase 2 trial.
739 Background: Ave 1LM is a recommended treatment option for patients (pts) with aUC without progression after 1L platinum-based chemotherapy (PBC). In the interim analysis of the JAVELIN Bladder Medley trial (NCT05327530), 1LM with Ave + sacituzumab govitecan (SG; Trop-2–directed antibody-drug conjugate) improved progression-free survival (PFS) vs Ave monotherapy (mono), thereby meeting the study’s primary endpoint. Here, we report the primary analysis in all study arms, including Ave + SG, Ave + M6223 (anti-TIGIT), and Ave + NKTR-255 (polymer-conjugated IL-15 agonist). Methods: Pts with unresectable locally advanced or metastatic UC without progression after 4-6 cycles of 1L PBC were randomized 1:2:2:2 to receive Ave mono (control), Ave + SG, Ave + M6223, or Ave + NKTR-255, stratified by presence of visceral metastases. Primary endpoints were investigator-assessed PFS and safety. Per protocol, PFS and overall survival (OS) data in the Ave mono arm for each comparison were extended using propensity score–weighted data from the JAVELIN Bladder 100 phase 3 trial (NCT02603432), which was additionally down-weighted to match the number of randomized pts. Results: 256 pts were randomized. Baseline characteristics were generally similar between arms. At data cutoff (Apr 28, 2025), median follow-up for OS was ≥16.8 months in all arms. Study treatment was ongoing in the Ave + SG, Ave + M6223, Ave + NKTR-255, and Ave mono arms in 20/74 (27.0%), 17/72 (23.6%), 22/73 (30.1%), and 8/37 (21.6%) pts, respectively. In the Ave + SG, Ave + M6223, Ave + NKTR-255, and Ave mono arms, treatment-related adverse events (TRAEs) of any grade (grade ≥3) occurred in 97.3% (71.2%), 76.4% (8.3%), 95.8% (20.8%), and 66.7% (5.6%) of pts, respectively. 2 pts had a TRAE that led to death (Ave + SG and Ave + NKTR-255 arms). PFS and OS results (including extended data in the Ave mono arm) are shown in the Table. Conclusions: In the primary analysis of the JAVELIN Bladder Medley trial, Ave + SG as 1LM in pts with aUC without progression after 1L PBC showed improved PFS vs Ave mono. While OS data are still immature, OS trends favored Ave + SG, Ave + M6223, and Ave + NKTR-255 vs Ave mono. No new safety signals were identified. Follow-up for OS is ongoing. Clinical trial information: NCT05327530 . Ave + SG (n=74) Ave mono (n=74) Ave + M6223 (n=72) Ave mono (n=74) Ave + NKTR-255 (n=73) Ave mono (n=74) Median PFS (95% CI), months 11.17(7.62-17.64) 3.75(3.32-5.65) 5.42(3.78-7.43) 4.50(3.45-7.20) 5.59(3.75-12.91) 4.50(3.48-7.20) Stratified HR (95% CI) 0.54(0.36-0.81) 0.95(0.64-1.39) 0.81(0.55-1.21) Median OS (95% CI), months NE(18.37-NE) 22.05(16.92-28.78) NE(19.45-NE) 23.23(17.68-30.82) NE(19.19-NE) 23.23(17.08-30.82) Stratified HR (95% CI) 0.69(0.41-1.17) 0.75(0.44-1.27) 0.67(0.39-1.14) HR, hazard ratio; NE, not estimable.