tbuckley/cabot-search huggingface dataset:
Abstract 4973: Assessing urban-rural differences in the outcomes of the most common cancers in Georgia: Incidence rates and stage at diagnosis
Authors: Amelito Manuel Andaya, A. Miguel Andaya, Stanley Atencah, Jason Holligan, Chinenye Egwuonwu
Journal: Cancer Research (2025)

Introduction: Lung, pancreatic, colon, prostate and breast cancers are the leading causes of cancer-related deaths in Georgia. Mortality is highest in rural counties which have higher poverty rates and larger composition of minority population. Our study aims to compare the proportion of the five most common cancers in Georgia that were diagnosed at late stages between urban and rural county locations. Methods: The National Institutes of Health State Cancer Profiles database was examined for incidence rates of breast, colon, lung, prostate and pancreatic cancers from 2017 to 2021 in Georgia. Age-adjusted incidence rates were calculated and stratified by county name, location and percentage at late stage of diagnosis. Late stage was defined as the presence of regional or distant metastases at the time of diagnosis. Results: Among women diagnosed with breast cancer, rural counties had a statistically significant higher percentage of late-stage diagnoses compared to urban counties. In contrast, no significant differences were observed in the incidence of late-stage diagnosis for colon, lung, prostate, or pancreatic cancers between rural and urban populations. Conclusion: The study demonstrated a statistically significant disparity in late-stage breast cancer diagnoses between rural and urban counties in Georgia. This emphasizes the need to improve early detection of this cancer that is alarmingly becoming more common. More attention should be given to these underserved communities given these findings. While no statistically significant rural-urban differences were found for other cancer types, further observational studies with more robust methodologies are needed in order to understand the observed incongruence in stage at diagnosis of breast and the other leading cancers in Georgia. Citation Format: Amelito Manuel Andaya, A. Miguel Andaya, Stanley Atencah, Jason Holligan, Chinenye Egwuonwu. Assessing urban-rural differences in the outcomes of the most common cancers in Georgia: Incidence rates and stage at diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4973.
Abstract 7316: QL615, a tetraspecific T cell engager with highly restricted activity on MET and EGFR-positive tumors while providing co-stimulation via CD2
Authors: Yanan Wang, Meihua Luo, Guangjie Guo, Shenda Gu, Joshua Morrissette, Nathan Ngo, Shihao Chen
Journal: Cancer Research (2025)

Abstract Effective targeting of solid tumors using T cell engagers remains challenging due to the lack of tumor specific antigens (TSA), and the difficulty in achieving sustained anti-tumor response. Frequently, target antigen expression is upregulated on cancer, yet low expression on normal tissues limits the therapeutic window. Moreover, the lack of co-stimulatory signals paired with CD3 in the tumor microenvironment often leads to T cell exhaustion and non-durable responses. To overcome these shortcomings, we have developed a tetraspecific T cell engaging platform, termed TECAD “T Cell Engager with Co-Stimulation Avidity Driven”, to address both tumor selectivity and potency by (1) activating T cells only when bound to tumor cells expressing paired antigens, and (2) providing CD3 co-stimulation via conditional CD2 activation. The latter enhances antitumor immune response and overcomes resistance to immune checkpoint blockade therapies. QL615, our lead TECAD candidate, targets MET and EGFR, two clinically validated targets limited by expression on normal tissues. MET and EGFR are typically expressed on non-overlapping normal tissues but frequently colocalized on tumors cells. We have optimized the affinity of MET and EGFR binding domains such that only dual engagement on the target cell provides high avidity binding AND-gated activation. Cell binding assays showed nanomolar EC50 on tumor cells expressing both MET and EGFR, whereas binding was negligible on cells expressing only low levels of either MET or EGFR. In vitro killing assays demonstrated over a 1000-fold selectivity in the lysis of double-positive tumor cells. The TECAD’s CD2-mediated co-stimulation enhanced in vitro killing of tumor cells ∼30-fold over constructs with CD3 redirection alone and showed superior tumor growth control in vivo. QL615 is currently advancing toward a development decision and clinical evaluation. Citation Format: Yanan Wang, Meihua Luo, Guangjie Guo, Shenda Gu, Joshua Morrissette, Nathan Ngo, Shihao Chen. QL615, a tetraspecific T cell engager with highly restricted activity on MET and EGFR-positive tumors while providing co-stimulation via CD2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7316.
Abstract 7302: A Novel Therapeutic Approach : New Drug Candidate with are potent and safe next-generation multi-target immune checkpoint inhibitor
Authors: Bo-Ram Lee, Seon-Boon Lee, Chul Joo Yoon, Hyunju Hwang, Sunho Jung, Joon Heo, Kyung-Mi Lee, H. Chris Kim
Journal: Cancer Research (2025)

Abstract Immune checkpoint inhibitors play a crucial role in current cancer treatments, serving as promising therapeutic options across various cancer types. In particular, PD-L1/PD-1 immune checkpoint inhibitors have been at the forefront of this field. However, recent concerns have been raised regarding the risk-benefit ratio of treatment based on PD-L1 expression levels, prompting the need for the development of immune checkpoint therapies that demonstrate high efficacy regardless of whether PD-L1 expression is high or low. Cellemedy’s T-sphaera platform based multi-target immune checkpoint inhibitors that simultaneously act on multiple immune targets, regardless of target expression levels. This platform offers several advantages: 1) it introduces biologically active domains that exhibit therapeutic effects, 2) it demonstrates high avidity based on protein structural characteristics, 3) it inherently possesses a cancer-T cell engaging effect when introducing multi-targets, and 4) being human protein-based results in reduced immune-related side effects, contributing to a favorable safety profile and therapeutic index. Cellemedy’s multi-target immune checkpoint inhibitors exhibit target-specific cytotoxicity against melanoma cancer cell line. In a non-human toxicity study, those compounds were well tolerated during repeated dosing, providing evidence of a superior safety profile without noticeable side effects. Furthermore, we verified strong efficacy in in vivo studies through T/NK cell engagement and high target avidity following a single-dose administration. Rapid and durable anti-tumor responses have been observed in vivo models. In summary, Cellemedy’s T-sphaera is promising multi-target immune checkpoint inhibitor platform that can be designed for various target, not only immune checkpoint blockade but also other tumor receptors, aiming at multiple cancers. Citation Format: Bo-Ram Lee, Seon-Boon Lee, Chul Joo Yoon, Hyunju Hwang, Sunho Jung, Joon Heo, Kyung-Mi Lee, H. Chris Kim. A Novel Therapeutic Approach : New Drug Candidate with are potent and safe next-generation multi-target immune checkpoint inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7302.
Prophylactic Weekly Efanesoctocog Alfa Versus Standard-Care Factor VIII in People Living With Severe Hemophilia A
Authors: Satoko Ito, Kunal C. Potnis, Jessica Preston Harvey, Manraj Sra, Jan Phillipp Bewersdorf, Robert D. Bona, Harlan M. Krumholz, Adam Cuker, Ankur Pandya, George Goshua
Journal: Annals of Internal Medicine (2025)

Prophylaxis goals for patients with severe hemophilia A encompass advancement toward the hemophilia-free mind (freedom from bleeding, pain, arthropathy, and treatment burden). Efanesoctocog alfa, the first ultra-long half-life factor VIII agent that enables once-weekly prophylaxis, shows a 77% improvement in annualized bleeding rate compared with standard-care factor VIII prophylaxis. To evaluate the conventional and distributional cost-effectiveness of prophylaxis with efanesoctocog alfa versus standard-care factor VIII (standard half-life and extended half-life) in the United States. Markov model. XTEND-1 study and other published sources. Patients with severe hemophilia A. Lifetime. U.S. health system and societal. Prophylaxis with efanesoctocog alfa versus standard-care factor VIII. Incremental cost-effectiveness ratio (ICER; cost per quality-adjusted life-year [QALY]) and threshold inequality aversion parameter (equity weight). Efanesoctocog alfa and standard-care factor VIII accrued 19.7 and 14.6 discounted lifetime QALYs at costs of $22.1 million and $11.2 million, respectively, with an ICER of $2.13 million per QALY. The distributional cost-effectiveness analysis (DCEA)-derived threshold equity weight was 6.9, exceeding commonly used U.S. equity standards. Results were consistent across all scenario analyses. Only the price of efanesoctocog alfa could change the conclusion. Efanesoctocog alfa needs to be priced at less than 53% of its current price for conventional cost-effectiveness and less than 59% for distributional cost-effectiveness. Standard-care factor VIII was favored in 100% of 10 000 probabilistic iterations. Benchmark equity weights (as opposed to hemophilia-specific weights) to interpret DCEA results. Prophylaxis with efanesoctocog alfa is not conventionally or distributionally cost-effective for severe hemophilia A in the United States at current pricing and equity weight thresholds. National Institutes of Health; National Heart, Lung, and Blood Institute.
Abstract 4964: Exploring women's healthcare barriers: impacts on adolescent HPV vaccination in Latino communities
Authors: Anju F. Kane, Lourdes Baezconde-Garbanati
Journal: Cancer Research (2025)

Abstract Objective: This study examines how barriers to healthcare faced by women influence HPV vaccination uptake among Latino adolescents in Los Angeles. Background: Human papillomavirus (HPV)-induced cervical cancer (CC) is a significant public health concern. Although routine HPV vaccination has been recommended in the United States for girls since 2006 and boys since 2011, disparities in vaccine initiation and completion persist, particularly among Latino adolescents in Los Angeles. Methods: Using data from the Es Tiempo campaign (2016-2018), this cross-sectional study analyzed responses from mothers of 353 Latino adolescents aged 9 to 26 years. Crosstabs were used to examine differences in vaccine initiation and completion by child sex and birth order. Logistic regression models were used to assess the association between parental healthcare barriers, such as lack of health insurance and access to a primary care provider (PCP), and HPV vaccination initiation. Results: Among the sample, 44% initiated the HPV vaccine, and 23% completed the series. Girls and firstborn children had higher vaccination rates compared to boys and later-born siblings. Lack of health insurance was associated with lower odds of vaccine initiation, while access to a PCP showed a modest positive effect on vaccination uptake. Conclusion: Women's healthcare barriers significantly contribute to HPV vaccination disparities among Latino adolescents in Los Angeles. Addressing issues such as limited health insurance access and implementing targeted interventions—especially for boys—could improve vaccination rates. Future research should explore how intersecting factors, including gender, socioeconomic status, education, and healthcare access, shape vaccination behaviors and outcomes. Citation Format: Anju F. Kane, Lourdes Baezconde-Garbanati. Exploring women's healthcare barriers: impacts on adolescent HPV vaccination in Latino communities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4964.
Abstract 5678: LC-HRMS based kinetic characterization platform for irreversible covalent inhibitor screening
Authors: Cai Fu, Tong Wu, Li Li, Tj (Tiejun) Bing
Journal: Cancer Research (2025)

Abstract Covalent inhibitors are recognized as indispensable parts in drug discovery and therapeutic researches. The irreversibility of covalent conjugation makes Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) a suitable tool for covalent inhibitor screening. LC-HRMS allows label-free, direct detection of the native protein and the covalent adduct in the sample, providing relative quantification of target engagement. Several methods have been developed for covalent screening using intact protein MS or peptide mapping, including binding site mapping, covalent binding rate determination and Kinact/Ki value measurement. In this study, the final protein concentration was 1.5 μM and the serial concentrations of positive control AMG510 were from 0.49 μM to 4.00 μM, and the total incubation time was 100 seconds. The intensity of the native protein and covalent adducts were collected on a QE Plus coupled with a C4 column. A relatively high binding rate was observed by intact mass analysis. And a sequence coverage of GDP-KRASG12C was above 75% using peptide mapping, the specific binding site was confirmed by MS2 data. Kinact/Ki value were fitted using more than six concentrations and five timepoints. This method was used for covalent inhibitors screening, binding site characterization and Kinact/Ki measurement. Citation Format: Cai Fu, Tong Wu, Li Li, Tj (Tiejun) Bing. LC-HRMS based kinetic characterization platform for irreversible covalent inhibitor screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5678.
Abstract 5787: Mutation prevalence in metastatic castration-sensitive prostate cancer based on metastasis timing and risk stratification
Authors: María Ovejero-Sánchez, Ana Jambrina, Ignacio González-Ginel, Daniel Tello, Manuel Balongo, Ana Gutierrez-Pecharroman, Pedro P López-Casas, Alfredo Rodríguez-Antolín, Elena Castro, David Olmos
Journal: Cancer Research (2025)

Abstract Introduction and Objectives: Metastatic castration-sensitive prostate cancer (mCSPC) is a clinically heterogeneous disease in which genetic mutations and tumor burden influence patient outcomes. Mutations in some DNA repair genes (e.g. BRCA1/2 and ATM) have been related to prostate cancer development and progression and may serve as therapeutic targets. The GENPRO12 study aims to evaluate the mutational profiles in non-mCSPC and mCSPC patients and to explore its clinical associations. Material and Methods: This preliminary report includes 109 mCSPC patients, stratified by synchronous/metachronous disease. Each group was further classified into risk/volume (high/low) categories based on CHAARTED and LATITUDE criteria. Tumor samples were collected and analyzed using next-generation sequencing (NGS) ACHILLES test (Olmos et al. Ann Oncol 2024) to identify mutations in 40 genes, including BRCA1/2, ATM, and other prostate cancer-related genes. Clinicopathological data were extracted from medical records. Results: Median age at diagnosis of mHSPC was 72 (range 47-92) with a median PSA 46.9 (0.3-3956). 90 patients had synchronous metastatic disease, 69 were CHAARTED high-volume, 76 were LATITUDE high-risk, and 25 had visceral metastases (17 in the lung only). All but 11 patients had at least 1 alteration in the genes analyzed. The most relevant altered genes are listed in the table. BRCA2, PTEN, RB1 Loss of Function (LoF) and MYC gain were more frequent in de novo and/or high-volume cases. Conclusions: Genetic alterations with prognostic and/or predictive value can be detected using prostate-specific NGS assays on archived diagnostic FFPE samples. Their prevalence may vary based on mCSPC clinical presentation, reflecting distinct disease biologies. Updated results, including outcomes and treatment responses, will be presented at the meeting. Citation Format: María Ovejero-Sánchez, Ana Jambrina, Ignacio González-Ginel, Daniel Tello, Manuel Balongo, Ana Gutierrez-Pecharroman, Pedro P López-Casas, Alfredo Rodríguez-Antolín, Elena Castro, David Olmos. Mutation prevalence in metastatic castration-sensitive prostate cancer based on metastasis timing and risk stratification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5787.
Abstract 7255: Novel anti-PD(L)1 resistance models for post-anti-PD(L)1 drug development
Authors: Hongyan Sun, Yan Wang, Zhu Fang, Jianming Xu, Xiang Gao, Jun Wang
Journal: Cancer Research (2025)

Abstract Although cancer immunotherapy utilizing blockade of the PD-1/PD-L1 checkpoint has revolutionized the treatment of a wide variety of malignancies, leading to durable therapeutic responses, it is ineffective in many patients who developed drug resistance after initial response. Therefore, the establishment of robust preclinical anti-PD-1 resistance models is of paramount importance for unraveling drug resistance mechanisms and developing novel treatment strategies. The mechanisms of anti-PD-1/anti-PD-L1 resistance include insufficient presentation of tumor antigens, downregulation of MHC class I molecules, dysregulated IFN-γ signaling pathways, and the immunosuppressive tumor microenvironment. GemPharmatech has established 3 models of anti-PD-1 resistance. (1) Drug induced model: BALB/c-hPD1 mice were subcutaneously transplanted with CT26 cells and treated with anti-PD-1 (KEYTRUDA®) twice weekly. Non-responsive tumors were excised, dissociated, cultured, and then re-implanted into naïve mice for anti-PD-1 treatment to maintain screening pressure. The induced model of anti-PD-1 resistance was obtained after repeated screening cycles. (2) Genetically engineered model: Engineered anti-PD-1 resistant models were established by knocking out either B2M or STK11 in CT26, which are known to confer specific genetic alterations to anti-PD-1 resistance. (3) Primary resistance model. CT26 cells acquired anti-PD-1 resistance after a series of KEYTRUDA treatment and re-implantation demonstrated a stable anti-PD-1 resistant phenotype. Compared with parental cell lines, drug-resistant CT26 cell showed a significantly faster tumor growth kinetics in vivo. RNA sequencing data revealed a set of genes disregulated between the resistant and parental cell lines, providing insight into the resistance mechanism to anti-PD-1 therapy. In the engineered PD-1-resistant CT26 model, knocking out STK11 dampen CT26's response towards anti-PD-1 treatment. After ablation of STK11, CD8+ cytotoxic T lymphocyte infiltration was decreased, and myeloid-derived suppressor cells (MDSCs) significantly accumulated in the tumor microenvironment. Additionally, STK11 deletion was associated with reduced PD-L1 expression in tumor cells, suggesting that immunosuppressive microenvironment contributed to the development of resistance. In conclusion, preclinical anti-PD-1 resistance models are valuable tools for researchers to dissect the complexity of anti-PD-1 resistance mechanisms and provide important guidance for the biomarker discovery as well as development of innovative therapeutic strategies. Citation Format: Hongyan Sun, Yan Wang, Zhu Fang, Jianming Xu, Xiang Gao, Jun Wang. Novel anti-PD(L)1 resistance models for post-anti-PD(L)1 drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7255.
Abstract 2515: Enhancing oncology data collection and submission: The value of the national cancer institute (NCI) oncology codetable mapping file
Authors: Karine Provost, Stephanie Le Goaller, Mathieu Grace, Pierre Montagne
Journal: Cancer Research (2025)

Abstract Data collection for efficacy endpoints in oncology clinical trials present various challenges and thus require adapted strategies and tools. Use of the Guidances to follow for surrogate endpoint analysis and reporting, such as RECIST, Lugano, RANO or others are straightforward, as this depends on the target malignancies and the type of compound being studied. It is however challenging to ensure that, once the endpoints for a trial are selected, the method for their collection and identification be clearly defined. This paper will focus on the use of the tools developed by the NCI and CDISC communities to ensure that data be efficiently collected and organized, in line with regulatory requirements. We will be explaining the role of the following tools which are used throughout a trial, starting with the protocol design and all the way until the final reporting:- CDASH Implementation Guide (CDASHIG) : this refers to the guidances for data collection- SDTM Implementation Guide (SDTMIG) : this refers to the guidances for data submission- Therapeutic Area User Guides (TAUGs) : these include disease-specific metadata, examples and guidances on implementing CDISC standards for a variety of uses, including global regulatory submissions (ie : Breast Cancer, Prostate Cancer, Colorectal Cancer, Lung Cancer) It is of particular interest to evaluate the value added of the NCI Oncology Codetable Mapping File in oncology clinical trials, as demonstrated through its use in EDC and database design. We will describe the approach taken to integrate this new tool into EDC and Database design and this enables further alignment with guidelines (e.g. RECIST, Lugano), controlled terminologies and Regulator expectations. We will also investigate the value added for investigator sites, who can benefit from this further standardization of data collection practices across clinical trials, regardless of sponsor or CRO, to simplify their working practices.As a conclusion, we will summarize the value added by the NCI Oncology Codetable Mapping File to the existing landscape (CDISC tools, Surrogate Endpoint Guidances) of oncology clinical trials. We will emphasize its potential to simplify complex data requirements for topics specific to the field of oncology. Citation Format: Karine Provost, Stephanie Le Goaller, Mathieu Grace, Pierre Montagne. Enhancing oncology data collection and submission: The value of the national cancer institute (NCI) oncology codetable mapping file [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2515.