tbuckley/cabot-search huggingface dataset:
CORE-008: A phase 2, multi-arm, multi-cohort, open-label study to evaluate intravesical cretostimogene grenadenorepvec in participants with high-risk non-muscle invasive bladder cancer.
Authors: Trinity Bivalacqua, Siamak Daneshmand, Neal D. Shore, Shreyas Joshi, Colin P.N. Dinney
Journal: Journal of Clinical Oncology (2025)

TPS901 Background: Treatment for patients with High-Risk Non-Muscle Invasive Bladder Cancer (HR NMIBC) consists of Transurethral Resection of Bladder Tumor (TURBT) followed by intravesical Bacillus Calmette–Guérin (BCG). Despite high initial response rates, over 50% of patients will recur and 20-40% are at risk for progression. Treatment of HR NMIBC is challenged by the BCG shortage, thus there exists a need for clinically effective, well-tolerated, and readily available treatment options for patients with HR NMIBC. Cretostimogene grenadenorepvec is an oncolytic immunotherapy with a dual mechanism of action. It selectively replicates and lyses bladder cancer cells with Retinoblastoma (Rb)-E2F pathway alterations. The subsequent release of virus- and tumor- specific antigens initiate antitumor immune activation amplified by the GM-CSF transgene, a potent cytokine. Cretostimogene received both Fast Track and Breakthrough Therapy Designations by the US FDA for the BCG-Unresponsive HR NMIBC with CIS indication. Given the strength of these data, the CORE-008 clinical trial ( NCT06567743 ) was developed as a Phase 2, multi-arm, multi-cohort trial to further evaluate the safety and efficacy of cretostimogene in patients with HR NMIBC. Methods: Eligibility criteria include pathologic confirmation of HR NMIBC as defined by the American Urologic Association (AUA) Guidelines. Cohort A (BCG-naive) is comprised of CIS +/- HG Ta/T1 participants who have not received prior BCG. Cohort B (BCG-exposed) will consist of CIS +/- HG Ta/T1 or papillary-only patients who have received prior BCG, and recurred either immediately after induction therapy (BCG-resistant) or recurred at a delayed timepoint, after adequate or inadequate BCG. Intravesical cretostimogene will be instilled in combination with n-dodecyl-β-D-maltoside (DDM), an excipient, that enhances adenoviral delivery, for six weekly doses during the induction phase, followed by three weekly maintenance cycles quarterly through month 12, then every six months through month 36. Re-induction is permitted. The primary endpoint for the CIS population is Complete Response (CR) at any time. High-Grade Event-Free Survival is the primary endpoint for papillary-only participants. Secondary endpoints will include Duration of Response, all-cause Event-Free Survival, Bladder Cancer Specific Survival, Radical Cystectomy Free Survival, and safety. Exploratory outcome measures include Health-Related Quality of Life, Overall survival, and biomarker assessments. Additional HR NMIBC cohorts are under development. Multiple clinical sites have been identified and Cohort B has received collaborative support from the Society of Urologic Oncology-Clinical Trials Consortium. Clinical trial information: NCT06567743 .
NGS-based molecular panel analysis of metastatic prostate cancer for daily routine: How often do we detect druggable mutations?
Authors: Olivia Steenbock, Constantin Rieger, Julian Heidenreich, Pia Paffenholz, David Pfister, Richard Weiten, Melanie von Brandenstein, Axel Heidenreich
Journal: Journal of Clinical Oncology (2025)

203 Background: Guidelines recommend molecular analysis to identify druggable mutations after failure of the first-line systemic therapy for metastatic prostate cancer (mPCA). We report our results of molecular diagnostics in mCRPC patients. Methods: From 2018 to 2023, 311 mCRPC patients underwent molecular panel analysis of archived prostatectomy samples (n=96) or CT-guided biopsies of progressive metastases (n=215) using standardized NGS procedures after the failure of first- or second-line systemic therapy. Mutation analysis was initially performed using NGS with a custom "Prostate Cancer Panel" of 18 multiplex PCR amplicons (AR, ATM, AURKA/MYC, BRCA1/2, CDK12, CTNNB1, DLL3, ETS family, FOXA1, FOXO1, MED12, PIK3CA, PTEN, RAD51C, TP53, Wnt-Pathway), generated using a GeneRead DNAseq Custom Panel V2 (Qiagen). Since 2023, we perform apply the TSO500 panel in selected cases. Analysis of HRD was performed by combining BRCA1 and BRCA2 mutations with the HRD score (Genomic ScarScore GSS) using the HANDLE HRD Focus Panel (Halo-shape Annealing and Defer-Ligation Enrichment, AmoyDx). The data were evaluated using the following thresholds: tumor cell content ≥ 30%, GScore positive at ≥ 50, HRD positive: GScore at ≥ 50 or BRCA1/2 category 4/5 mutation. In addition MSI-high and mutations of MSH2, MSH6, PMS2, and MLH1 were analysed. The following databases were reviewed to identify druggable mutations: OncoKB, ClinVar, JAX-CKB, COSMIC, and My Cancer Genome. Results: Out of 311 biopsies, 299 (96%) had sufficient DNA content for NGS. NGS was performed from prostate (31%), lymph node (30%), visceral (15%), and bone (24%) metastases with informative DNA retrival in 95%, 95%, 92%, and 85%, respectively. Overall, 157 patients (50.5%) had no or non druggable mutations, while 154 patients (49.5%) exhibited druggable mutations. HRD gene mutations (BRCA1/2, ATM, CDK12, CHEK2, FANCA, Rad51C) and inactivating p53 mutations were observed in 66 patients (22%). 3 patients had p53 mutations with gain-of-function resulting in ATM inactivation. 50% HRD gene mutations including a positive HRD score were pathogen and treated with PARPi resulting in a progression-free survival of 3-28 months. Activating androgen receptor mutations and inactivating PTEN/activating PIK3Ca mutations were found in 42 (14%) and 24 (8%) patients, resp. Switch of treatment for AR mutation resulted in PFS of 6-9 months. Mismatch repair deficiency/MSI high mutations were identified in 3 cases who received pembrolizumab with a PFS of 4-8 months. Conclusions: NGS analysis in mCRPC reveals mutations in two-thirds of patients, of which 41% are already druggable. Only 50% of druggable mutations are based on BRCA1/2 or ATM. NGS analysis should be integrated into the diagnostic armamentarium following failure of first-line systemic therapy for mCRPC.
The impact of social vulnerability on perceived health in individuals with bladder cancer.
Authors: Karan Jatwani, Seyedeh Azadeh Miran, Philip Ma, Michael Joseph Whalen, Maneesh Rajiv Jain, Atulya Aman Khosla
Journal: Journal of Clinical Oncology (2025)

678 Background: Bladder cancer is the sixth most common malignancy in the United States. Social determinants of health (SDOH) have been increasingly recognized as drivers of disparities in cancer care. Improved understanding of the role of social vulnerabilities could better inform the cancer care delivery interventions towards equitable cancer care for bladder cancer patients. We aimed to study the impact of key SDOH measures (everyday discrimination, supportive relationships, neighborhood characteristics, and food and housing security) on the perception of overall health in bladder cancer patients using a publicly available database. Methods: A cross-sectional study was conducted using overall health and SDOH survey data collected by the National Institutes of Health All of Us Research Program from June 2017 to June 2022. Ordinal logistic regression was utilized to assess associations between overall perception of health and each specific SDOH survey domain. All statistical tests were two-sided, and a p-value less than 0.05 was statistically significant; multiplicity adjustments were not made. The Statistical package (0.13.5) of Python (Version 3.1) was used for all statistical analyses. Results: 1,796 participants with bladder cancer met the inclusion criteria. 640 (38.58%) had completed the SDOH surveys and were considered for analysis. Of the total population, there was a significant male preponderance (66.1% vs 31%). 559 (87.3%) were White, 3.4% Black or African American, and 3.6% with Hispanic ethnicity. In the ordinal logistic regression models. for every unit increase in the score of the supportive relationships SDOH domain (more supportive relationships), participants were 4% (OR = 1.04, 95% CI = [1.018, 1.053], p&lt;0.0001) more likely to have a higher perception of general health. Similarly for every unit increase in the food and housing security domain (more secure food and housing status), participants are 19% ((OR =1.19, 95%CI= [1.06,1.34], p 0.004) more likely to have a higher perception of general well-being. Controlling for all other variables, Black race, Hispanic ethnicity, smokers, and age less than 65 years were independently significant for poor perception of overall health (p &lt; 0.05). Conclusions: This is one of the first studies evaluating the role of each component of SDOH on the perception of overall health in bladder cancer patients. Our study demonstrates a clear predictive link between social determinants of health and the perceived overall health of bladder cancer patients. Specifically, stronger social support networks and secure access to food and housing were significantly associated with a more positive perception of health. These findings suggest that future directions in bladder cancer care should prioritize the development and implementation of comprehensive care models that address these social needs.
Racial disparities in secondary metastasis in patients with bladder cancer: A 5-year National Inpatient Sample study.
Authors: Sakditad Saowapa, Natchaya Polpichai, Manasawee Tanariyakul, Chalothorn Wannaphut, Chanakarn Kanitthamniyom, Hector J Garcia Pleitez, Diego Alonso Olavarria Bernal, Watsachon Pangkanon, Vivie Tran, Pharit Siladech, Lukman Aderoju Tijani
Journal: Journal of Clinical Oncology (2025)

671 Background: Bladder cancer is one of the most common cancers globally, with significant variations in disease outcomes observed across racial groups. Secondary metastasis plays a critical role in determining disease prognosis and overall survival in bladder cancer patients. However, racial disparities in the metastatic progression of bladder cancer remain underexplored. This study aims to investigate how race influences the patterns of metastasis in bladder cancer patients using a large national database. Methods: A retrospective analysis of the National Inpatient Sample (NIS) from 2016 to 2020 was performed to identify adults diagnosed with bladder cancer using ICD-10 codes. Patients were categorized based on the presence of metastasis. Multivariable logistic regression models were used to assess the impact of race on secondary metastasis to key organ systems, including the lung, liver, bone, and brain, while adjusting for potential confounders. Caucasians were used as the reference group, and statistical significance was defined as p-values ≤ 0.05. Results: The study cohort included 411,360 patients with bladder cancer, of whom 66,805 (16.2%) had secondary metastasis. The mean age of patients with metastasis was significantly lower (71.00 years, 95% CI: 70.78–71.22) compared to those without metastasis (74.02 years, 95% CI: 73.90–74.14) (p &lt; 0.001). Racial disparities were observed, with African American patients having higher odds of lung metastasis (OR 1.23, 95% CI: 1.11–1.38, p &lt; 0.001) and liver metastasis (OR 1.18, 95% CI: 1.05–1.33, p = 0.005). Asian patients were more likely to develop bone metastasis (OR 1.29, 95% CI: 1.13–1.47, p &lt; 0.001) and brain metastasis (OR 1.46, 95% CI: 1.03–2.09, p = 0.036). Other factors associated with higher metastasis risk included radiation therapy (OR 3.71, 95% CI: 2.16–6.38, p &lt; 0.001), while comorbidities like diabetes (OR 0.64, p &lt; 0.001) and hypertension (OR 0.86, p &lt; 0.001) were associated with lower odds of metastasis. Conclusions: This study highlights significant racial disparities in the metastatic progression of bladder cancer, with African American and Asian patients showing higher odds of metastasis to key organ systems compared to Caucasians. These findings underscore the need to consider racial differences in the clinical management and treatment strategies for bladder cancer patients. Further research is required to explore the underlying causes of these disparities and their impact on long-term survival.
Global and regional burden of kidney cancer: Analysis and future predictions based on GBD data from 1990 to 2021.
Authors: Haochen Zhao, Qiang Wei
Journal: Journal of Clinical Oncology (2025)

521 Background: Kidney cancer, as a common urological malignancy with poor prognosis, shows significant variations in incidence and mortality rates in different countries and regions worldwide. This study aims to investigate the global burden and trends of kidney cancer from 1990 to 2021, and to analyze its associations with various factors. Methods: First, data on the number of kidney cancer cases and age-standardized rates (ASR) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021 were collected and analyzed globally. Subgroup analyses based on sex, country, region, and sociodemographic index (SDI) were then performed to examine the current status and time trends from 1990 to 2021 of kidney cancer in the total population and various subgroups. In addition, the age-period-cohort (APC) and Bayesian age-period-cohort analysis (BAPC) models were used to track dynamic changes in disease burden and predict future trends of the above indicators. Finally, risk factors and trend changes related to kidney cancer mortality within SDI subgroups were analyzed. Results: Globally, the incidence of kidney cancer increased sharply from 1.6×10 5 in 1990 to 3.9×10 5 in 2021. The ASRs for all measures of kidney cancer burden were higher for men than for women. China has the highest number of cases, deaths and DALYs in 2021, followed by the United States. The country of Cabo Verde and the region of Western Europe have the fastest growing ASRs for both incidence and mortality. 49 countries or regions, mainly in Western Europe and North America, have a decreasing trend in ASR for mortality over the period. Overall, the burden of kidney cancer increased with higher SDIs, with countries with middle and low-middle SDIs having the fastest growing burden of kidney cancer, such as North Africa and the Middle East. The APC and BAPC models predicted a steady decline in the ASRs of incidence, prevalence, mortality and DALYs for kidney cancer over the next 20 years, although the APC model predicted a continued steady increase in the absolute numbers of these indicators. In addition, high BMI and smoking were identified as the major risk factors contributing to kidney cancer deaths. High body mass index was particularly pronounced in countries with low SDIs. Conclusions: From 1990 to 2021, the incidence of kidney cancer has declined from historical peaks in developed countries, but remains on an upward trend in developing countries and represents a significant health threat. Revealing some previously unreported findings, the formulation of appropriate policies to reduce population exposure to risk factors associated with kidney cancer could be beneficial in the context of global aging trends.
ProstACT GLOBAL: A phase 3 study of <sup>177</sup> Lu-rosopatamab (TLX591) with and without the best standard of care for patients with PSMA expressing metastatic castration-resistant prostate cancer progressing despite prior treatment with a novel androgen axis drug.
Authors: Alton Oliver Sartor, Scott T. Tagawa, Nat Lenzo, David Cade, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2025)

TPS303 Background: The treatment of advanced prostate cancer (PC) is challenging, with undesirable side effects that impact patient quality of life. Radioimmunotherapy (RIT) can localize therapy to specific tumor cells in multiple organs to reduce or eliminate damage to normal tissue. The cell surface glycoprotein prostate-specific membrane antigen (PSMA) is an ideal therapeutic target as it is highly expressed by malignant prostate cells. There is a strong rationale for further investigation of the 177 Lu-labeled, chelator-conjugated antibody, 1 77 Lu-rosopatamab, as a potential first-line RIT candidate for the treatment of PC. Methods: This multinational, multicenter, prospective, randomized, open label phase 3 study will have 2 parts: a dosimetry and safety lead-in (n=30) and a randomized treatment expansion (n=490). In Part 1, patients will be divided into 3 groups (n=10 each) to receive 2 single intravenous (IV) injections of 76 millicuries (mCi) each, 14 days apart, of 177 Lu-rosopatamab with best standard of care (SoC) combinations with abiraterone, enzalutamide, or docetaxel to fully characterize biodistribution and safety profiles of 177 Lu-DOTA-rosopatamab + SoC combinations. SoC received will be determined prior to treatment with 177 Lu-rosopatamab. In Part 2, patients will be enrolled in a 2:1 ratio to receive either the best SoC or 2 single IV injections of 76 mCi each (equivalent to a 45 mCi/m 2 dose in a standard 1.7m 2 individual) of 177 Lu-rosopatamab, given 14 days apart, plus best SoC. SoC will be determined prior to randomization, and a change in planned SoC will not be permitted. Eligible patients must have PSMA-expressing metastatic castration-resistant PC (mCRPC) that have progressed despite prior therapy with either enzalutamide or abiraterone plus prednisone, and 1 line of prior taxane therapy or have refused or are ineligible for taxanes. Patients must have adequate organ function including at least 150x10 9 /L platelets, hemoglobin 10 g/dL, and have PSMA-positive disease on 68 Ga-PSMA-11 PET/CT imaging as confirmed by a central reader. Key exclusion criteria include small cell histology, increased risk of hemorrhage or bleeding, known brain or hepatic metastases, or history of stroke, seizure, or treatment with radioisotopes within 6 months prior to randomization. The primary endpoint is radiographic progression-free survival. Key secondary endpoint is OS. Additional secondary endpoints include 5-year overall survival, tumor objective response rate, time to symptomatic skeletal event, and health-related quality of life. Clinical trial information: NCT04876651 .
Phase 1/2 OMAHA-01A substudy of oral CYP11A1 inhibitor opevesostat alone or in combination with other therapies for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Arif Hussain, Chris Garratt, Nan Li, Yingjie Liu, Christian Heinrich Poehlein, Peter C.C. Fong
Journal: Journal of Clinical Oncology (2025)

TPS300 Background: Current treatments for mCRPC are associated with hormone dependence and the development of resistance. Therapeutic agents with novel mechanisms of action are needed for this patient population. Opevesostat (MK-5684; ODM-208) is an oral, nonsteroidal inhibitor of cytochrome P450 11A1 (CYP11A1), a catalyst of the first and rate-limiting step of steroid biosynthesis. In the phase 1/2 CYPIDES study, opevesostat demonstrated antitumor activity in patients with heavily pretreated mCRPC (1). OMAHA-U01 is an adaptive, open-label, rolling-arm, multicenter, phase 1/2 umbrella study that will evaluate the safety and efficacy of opevesostat-based investigational therapies in prostate cancer. Substudy 01A (NCT06353386) will evaluate opevesostat alone or in combination with other therapies in patients with previously treated mCRPC. Methods: Eligible patients have mCRPC that progressed during ADT ≤6 months before screening, and on/after 1-2 NHAs for metastatic or nonmetastatic hormone-sensitive prostate cancer and nonmetastatic or mCRPC. Prior treatment with ≤1 taxane for mCRPC is allowed. A safety lead-in phase for all opevesostat-based experimental combinations (~10 patients in each arm) will establish the recommended phase 2 dose (RP2D), followed by an efficacy phase (opevesostat alone, ≤100 patients; opevesostat-based combinations, ~40 patients each). Patients will be randomly assigned 1:1:1:1 to opevesostat 5 mg PO BID, opevesostat 5 mg PO BID + olaparib (RP2D), opevesostat 5 mg PO BID + docetaxel (RP2D), and opevesostat 5 mg PO BID + cabazitaxel (RP2D). The primary endpoint for the safety lead-in phase is safety and tolerability. Primary endpoints for the efficacy phase are safety and prostate-specific antigen response rate per Prostate Cancer Working Group criteria. 1. Fizazi et al. NEJM Evid. 2024. Clinical trial information: NCT06353386 .
Circulating tumor DNA (ctDNA) monitoring in the assessment and prediction of the efficacy of PARP inhibitors (PARPi).
Authors: Diwei Zhao, Junliang Zhao, Yuanwei Li, Xinyang Cai, Zhenyu Yang, Fangjian Zhou, Yonghong Li, Jun Wang
Journal: Journal of Clinical Oncology (2025)

TPS307 Background: PARP inhibitors (PARPi) emerged as an promising treatment for metastatic castration-resistant prostate cancer (mCRPC) patients with BRCA1/2 mutation. However, prediction of treatment response remains a challenge. Still, some patients with mutations other than BRCA1/2 responded to PARPi. Circulating tumor DNA (ctDNA) is a promising biomarker that can offer real-time insights into tumor dynamics, allowing for non-invasive monitoring of therapeutic efficacy. This study aims to assess ctDNA monitoring as a predictor of response and relapse for mCRPC patients receiving PARPi. Methods: This trial is an open-label, single-center, observational, prospective cohort study. This study intends to enroll 30 male mCRPC participants aged 18 to 75 years, who have progressed from second-line treatment at mCRPC stage and exhibit homologous recombination deficiency (HRD) or carrying DNA damage repair (DDR) gene mutations. The study involves whole blood and tumor tissue sampling for ctDNA detection, homologous recombination repair (HRR) gene testing, and whole exome sequencing. The primary outcomes include radiological progression-free survival (rPFS), objective response rate (ORR), and PSA response rate, with overall survival (OS) as a secondary outcome. The Institutional Review Board of Sun Yat-sen University Cancer Center approved this study. Recruitment is ongoing, with a target follow-up duration of 12 months and 26.7% (8/30) of the target sample size achieved. Data analysis is expected to commence in 2025 upon completion of recruitment. Clinical trial information: NCT05116579 .