bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase 2 study of concurrent cisplatin, capecitabine and celecoxib with radiotherapy in patients with carcinoma of the oesophagus.
Authors: Srivastava Kirti , Khalid Bushra , Tuteja Jasmeet Singh , Verma Mranalini , Bhatt Madan Lal Brahma
Published: July 2024

e16078

Background: Oesophageal cancer is the fourth common cause of cancer-related deaths in India. Definitive Chemoradiotherapy is standard for non-metastatic Squamous cell carcinoma of the oesophagus cancer. Chemoradiotherapy when given as definitive treatment is more effective than radiotherapy or chemotherapy alone. This treatment is usually offered to patients who are unsuitable for surgery. Unsuitability for surgery might be due to the extent of disease precluding the likelihood of a curative resection, or because the patient is physiologically not fit for surgery because of comorbidities or poor performance status. The aim of the present study was to analyse the effect of definitive concurrent chemo-radiotherapy in oesophageal cancer patients and assessment of toxicity profile and response. Methods: In the present Phase II study total 22 patients were recruited who had non-metastatic histologically confirmed carcinoma of the oesophagus selected for definitive chemoradiotherapy were enrolled. Chemotherapy consisted of three-weekly cycles of Inj. Cisplatin 60 mg/m2 given on D1, Tab. Capecitabine 625 mg/m2 given BD on D1-D21, and Tab. Celecoxib 200mg given BD on D1-D21. The planned protocol involved four cycles of concurrent chemotherapy. Radiotherapy in a dose of 50.4 Gy in 28 fractions was initiated on D1 of the second cycle of concurrent chemotherapy, or latest by D1 of the third cycle of concurrent chemotherapy. Results: In this Phase 2 study, 22 patients with a mean age of 55.68 ± 11.23 years, were treated. The tumor length averaged 6 ± 2.25 cm, with most common Stage III (52.17%), followed by Stage II (34.78%), Stage I (8.69%), and Stage IVA (4.34%). Grade 3 dysphagia was predominant (56.52%), followed by Grade 2 (34.78%), Grade 1 (4.35%), and Grade 4 (4.35%). During treatment, notable grade 1-2 toxicities included esophagitis(68%), fatigue(63%), nausea (54%), neutropenia (31%), anemia (22%), mucositis(18%), diarrhoea(13%), dermatitis(9%). There was gradual decline in the severity of dysphagia of all patients. Of the 8 patients evaluated for response with a median follow up of 12 months, the complete response rate was 25%, partial response rate was 25% and 37.5% showed stable disease whereas 12.5% developed progressive disease. The median overall survival is yet to be estimated. Conclusions: A notable clinical response, indicating a substantial treatment effect was observed. While some treatment-related toxicities were present, This approach shows potential in the treatment of oesophageal carcinoma. However, this study is still ongoing and it would be hasty to draw definitive conclusions.
Real-world treatment switching and sequencing to next line of therapy of zanubrutinib, acalabrutinib, and ibrutinib in CLL/SLL.
Authors: Pinilla-Ibarz Javier , Xue Mei , Wu Elizabeth , Esselman Kaitlyn , Furnback Wesley , Challagulla Swetha , Yang Keri
Published: July 2024

e19022

Background: Evaluating use of Bruton tyrosine kinase inhibitors (BTKis) for the treatment of CLL/SLL is crucial to understand real-world outcomes of these therapies in diverse populations. The objective of this study was to evaluate real-world switching and sequencing to next line of therapy in patients (pts) initiating BTKis as first-line (1L) or second-line (2L) CLL/SLL treatment. Methods: A retrospective study was conducted using IntegraConnect PrecisionQ to identify adult pts with ≥1 diagnosis for CLL/SLL initiating zanubrutinib (zanu), acalabrutinib (acala), or ibrutinib (ibru) in 1L or 2L between 1/1/2020-2/28/2023 (index period). Index date was defined as date of BTKi initiation. Pts were required to be continuously enrolled for ≥30 days pre- and post-index date. Treatment switching was measured as pts initiating another treatment within same line or advancing to next line of therapy within 90 days. Sequencing to next line of therapy was calculated from time to next treatment Kaplan-Meier curve, censoring patients at end of follow-up, and reported as proportion of pts receiving next line of therapy at 180 days. Results: 2,816 pts initiated a 1L BTKi (zanu=157; acala=1,238; ibru=1,421) and 1,253 initiated a 2L BTKi (zanu=107; acala=672; ibru=474). No major differences were observed in baseline demographic and clinical characteristics among 1L and 2L BTKi cohorts. Median follow-up in 1L was 123 days for zanu, 406 days for acala, and 637 days for ibru. Regardless of line of therapy, switching rate at ≤60 days and 61-89 days was statistically significantly lower for pts receiving zanu vs acala and ibru (P<0.0001, both 1L and 2L) (Table). Proportion of pts receiving next line of therapy at 180 days was lower for zanu vs acala and ibru (1L P=0.2958; 2L P<0.0001) (Table). Conclusions: Zanu pts had significantly lower switching rate within 90 days and lower proportion of pts receiving next line of therapy at 180 days when compared with acala and ibru in 1L and 2L. Longer follow-up and larger zanu sample size are required for a comprehensive assessment of treatment outcomes associated with use of BTKis in CLL/SLL. [Table: see text]
Risk of stroke in patients with atrial fibrillation and chronic lymphocytic leukemia.
Authors: Yetiskul Ekrem , Rizvi Taqi , Khan Shahkar , Khan Salman , Alomari Omer , Agarwal Alaukika , Asmar Samer , Sah Sajan , Khattar Georges , Grabie Yisroel , Saliba Fares , Matra Amanda Marie , Mokhtar Asmaa , Dhar Meekoo , Bershadskiy Alexander , Khan Danyal F. , Mustafa Ahmad , Spagnola Jonathan , Parikh Valay K.
Published: July 2024

e19030

Background: There has been a noticeable increase in the incidence of Atrial Fibrillation (AF) in patients with Chronic lymphocytic leukemia (CLL), especially patients treated with first-line therapy medications such as ibrutinib. However, these patients' risk of thromboembolic events is not well defined. Methods: Data for hospitalized patients with AF was obtained from The National Inpatient Sample (NIS) database from 2016-2018. Baseline risk factors were identified using ICD-10 codes. Patients who were already on anticoagulation were excluded. A logistic regression model was used to establish the relationship between variables and to adjust for underlying risk factors. The primary outcome was ischemic stroke between CLL and non-CLL patient cohorts. Results: The total number of patients was 1784456, out of which 1171644 patients were included in the study. There were 1165283 patients without CLL and 6361 with CLL. AF patients with CLL had more males (62.5% vs. 37.5%; P<.001), were older (74.6 vs. 78.82; P<.001), and had a lower prevalence of diabetes, hypertension, coronary artery disease, and hyperlipidemia. Pre-match analysis showed a lower rate of stroke in patients with AF and CLL compared to those without CLL (2.7% vs 4.2%; p<0.001). Post-match analysis revealed similar results with a lower risk of strokes in patients with CLL (4% vs 2.7%; p<0.001). Binary logistic regression analysis for primary and secondary outcomes revealed similar results pre-match and post-match. Patients who have AF and CLL had lower rates of stroke compared to those without CLL (OR: 0.647(0.530–0.790); p<0.001). Conclusions: AF patients with CLL were associated with a lower risk of ischemic stroke compared to those without CLL despite a higher risk profile as assessed by traditional risk factors. These findings should be considered while making decisions for therapies for the prevention of thromboembolic events.
Cardiovascular and hematologic complications of Hodgkin vs non-Hodgkin lymphoma and readmission trends: A National Readmission Database analysis from years 2016-2020.
Authors: Pokhriyal Sindhu Chandra , Alruwaili Waleed , Yadav Ruchi , Bellamkonda Amulya , Aryal Binit , Chowdhury Tutul , Panigrahi Kalpana , Kalavar Madhumati R. , Avezbakiyev Boris
Published: July 2024

e19034

Background: Cardiovascular complications are a leading cause of non-malignant death in lymphoma survivors. We sought to analyze the national readmission trends and evaluate the in-hospital mortality as well as the cardiovascular and hematological complications in lymphoma patients using the National Readmission Database (NRD). Methods: We selected patients aged >=18 years of age, from the NRD between the years 2016-2020 to generate a cohort of Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL) patients using ICD-10 codes. The primary outcome was in-hospital mortality, and the secondary outcome was cardiovascular and hematologic complications of HL vs NHL after adjusting for demographic confounders. We used multivariate logistic regression and propensity score matching (PSM) using STATA v.18. We also analyzed the 30-day readmission trends in these patients. Results: A total of 1,016,338 NHL and 83,036 HL patients were included in the analysis. After matching for demographics confounders, on PSM analysis we found that in-hospital mortality was higher in NHL vs HL (5.9% vs 4.42%; p-value 0.001). The cardiovascular complications that were studied included cardiac tamponade (0.69% in NHL vs 0.4% in HL; p-value 0.001), pericarditis (0.13% in NHL vs 0.14% in HL; p-value 0.717) and anthracycline cardiomyopathy (0.47% in HL vs 0.85% in NHL; p-value 0.001). The hematological outcomes studied included myelodysplastic syndrome (0.71% in NHL vs 0.64% in HL; p-value 0.210), acute leukemia (0.48% in NHL vs 0.44% in HL; p-value 0.43), and myelosuppression (18.59% vs 13.73%; p-value 0.001). A 30-day readmission trend analysis showed a longer length of stay in NHL vs HL (5.34 days vs 4.77 days) while the total inflation-adjusted cost was higher in HL vs NHL (20,989 dollars vs 17176 dollars). Conclusions: An NRD analysis of NHL and HL patient populations from 2016-2020 reflected a slightly increased mortality rate, higher incidence of cardiovascular complications and a longer length of stay in NHL patients. [Table: see text]
Phase I safety and preliminary efficacy of IMM0306 in combination with lenalidomide in patients with relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma.
Authors: Liu Yanyan , Lin Ningjing , Yao Zhihua , Zhang Jiuyang , Meng Wei , Wang Zhenjiu , Lu Qiying , Tian Wenzhi , Song Yuqin , Zhu Jun
Published: July 2024

e19040

Background: The combination of rituximab (anti-CD20 mAb) and lenalidomide was approved for use in relapsed or refractory (R/R) indolent non-Hodgkin's lymphoma (iNHL). IMM0306 is a fusion protein of CD20 monoclonal antibody with the CD47 binding domain of SIRPα on both heavy chains. It exerts excellent cancer killing efficacy by activating both macrophages and NK cells via blockade of CD47-SIRPα interaction and FcɣR engagement. Here, we report on a Phase I study of 8 patients (pts) with R/R CD20-positive B-cell NHL. Methods: This is an open-label, multicenter phase I study (NCT05771883). The study is designed to use "3+3" scheme for dose escalation exploring in 2 dose levels of IMM0306 (1.6 mg/kg, 2.0 mg/kg), intravenously administered each week in each 28-day cycle; while lenalidomide will be administered as fixed dose of 20 mg for NHL, taken orally once daily for the first 21 days of each 28-day cycle to determinate maximum tolerated dose (MTD). Dose-limiting toxicity (DLT) was evaluated in the first 28 days of the combination therapy. Safety was evaluated per CTCAE 5.0, tumor assessments performed once every 8 weeks by Lugano 2014. Results: As of Jan 5, 2024, 8 pts with R/R follicular lymphoma (FL, n=6) and marginal zone lymphoma (MZL, n=2) were enrolled. The median age was 52.5 years with 7 (87.5%) males. The median prior line of therapy was 1. All pts received previous anti-CD20 therapy. Among 7 efficacy evaluable pts, 1 CR (FL), 4 PR (2 FL, 2 MZL), and 1 SD were seen. The ORR and DCR were 71.4% and 85.7%, respectively. Two DLTs (grade 4 PLT decreased without bleeding) were observed at 2.0 mg/kg IMM0306 + 20 mg Lenalidomide dose level, but none at the dose level of 1.6 mg/kg IMM0306 + 20 mg Lenalidomide. The most common treatment related adverse events (TRAEs) were lymphocyte decreased (62.5%), ANC decreased (62.5%), WBC decreased (50%), anemia (50%), bilirubin increased (50%), PLT decreased (37.5%), infusion-related reactions (37.5%). Grade ≥3 TRAEs occurred in 6 pts, including lymphocyte decreased (62.5%), PLT decreased (25%), WBC decreased (12.5%), ANC decreased (12.5%) and pneumonia (12.5%). One pt experienced treatment related serious adverse event. 5 patients experienced TRAEs, leading to the study drug interruption, while no patients experienced TRAEs leading to the study drug discontinuation or death. 2 pts had a dose reduction of IMM0306 (2.0 mg/kg dose level), 3 pts had dose reductions of lenalidomide due to TRAEs. Pharmacodynamics analysis demonstrated IMM0306 combine lenalidomide effectively depleted B cell in peripheral blood within 24 hours. Conclusions: 1.6 mg/kg IMM0306 in combination with 20 mg lenalidomide was well-tolerated and with a robust preliminary anti-tumor activity in pts with R/R FL and MZL. The phase I study is ongoing. Clinical trial information: NCT05771883 .
Orelabrutinib, rituximab, temozolomide and high-dose methotrexate (RMOT) in newly diagnosed primary central nervous system lymphoma (PCNSL): A retrospective analysis on efficacy and safety.
Authors: Xia Yi , Cai Qingqing , Zhang Peng , Tian Xiaopeng , Fang Xiaojie
Published: July 2024

e19041

Background: PCNSL is a rare, aggressive malignant tumor and has a poor prognosis. HD-MTX-based regimen is the first-line treatment of PCNSL. Orelabrutinib is a novel, potent, highly selective BTK inhibitor with a high CSF concentration. Recent evidence has shown the efficacy and safety of orelabrutinib in PCNSL. Therefore, we conducted a retrospective study of clinical outcomes in newly diagnosed PCNSL patients (pts) treated with RMOT regimen in routine clinical care. Methods: This retrospective cohort included the pts (aged 18-80 years) with newly diagnosed PCNSL who received 6 cycles of RMOT regimen (rituximab 375 mg/m2 iv day 1; MTX 3.5 g/m2 iv day 1; temozolomide 150 mg/m2 po day 1 to day 5; orelabrutinib 150 mg qd po; 4 weeks per cycle) as the first-line induction therapy between Nov. 2021 and Aug. 2023. All the pts were proposed to receive orelabrutinib monotherapy as maintenance after RMOT therapy. We recommend to receive autologous stem cell transplantation (ASCT) or whole brain radiation therapy (WBRT) as consolidation after RMOT therapy. Efficacy was assessed by MRI/PET per the International PCNSL Collaborative Group (IPCG) criteria. The primary endpoint was overall response rate (ORR); secondary endpoints were CR rate, progression-free survival (PFS), overall survival (OS), and safety. Results: Ten pts (6 males) with PCNSL were included, with a median age of 61 years (range, 45-77). All pts had a histologically confirmed diffuse large B-cell lymphoma. 4 pts (40%) underwent WBRT after induction therapy. As of the cut-off date (December 31, 2023), the median follow-up time was 9.7 (range, 4.8-25.7) month. All pts were evaluated for the treatment response. An interim evaluation after 4 cycles was available for 10 pts, showing complete remission (CR) rate of 80% (8/10), partial response (PR) rate of 20% (2/10), giving an ORR of 100.0% (10/10, Table). At data cutoff, the best ORR was 100.0% (10/10), with all pts achieved CR. Of 10 responders, 9 had an ongoing response, and 1 died of covid-19 infection. Median PFS/OS was not reached (NR) (95% CI NR-NR). The most common AEs were anemia, other include white blood cell or platelet count decreased. Reported AEs were generally manageable and resolved soon after supportive treatment. Only 1 (10%) pts experienced ≥grade 3 AEs—acute kidney injury. No treatment-related death occurred. Conclusions: This retrospective data suggested that RMOT had an encouraging anti-tumor activity in newly diagnosed PCNSL pts, with a toleratable safety profile. This orelabrutinib-containing regimens may provide a potential treatment strategy for pts with PCNSL. [Table: see text]
Impact of rituximab maintenance on survival of patients with mantle cell lymphoma: A north Indian tertiary care center experience.
Authors: Datta Soumyadeep , Gogia Ajay , Wig Naveet , Sagiraju Hari Krishna Raju , SHARMA ATUL , Mallick Saumyaranjan , Gupta Ritu
Published: July 2024

e19047

Background: Mantle cell lymphoma (MCL) is an aggressive variant of non-Hodgkin lymphoma. Indian data is scarce owing to its rarity in south-east Asia. Till now, studies have not shown overall survival benefit with rituximab maintenance (RM). Our study aims to assess if RM improves overall survival of MCL patients. Methods: We retrospectively analysed clinicopathological data of 90 transplant-ineligible MCL patients treated between January’2013-December’2023 at Institute Rotary Cancer Hospital - All India Institute of Medical Sciences, New Delhi, India. Rituximab-based induction chemotherapy was used in all patients as per institutional protocol. RM was used in twenty-eight (31.0%) patients due to financial constraints. Primary outcome was overall survival (OS). Secondary outcomes were event free survival (EFS) and factors affecting OS, EFS. OS was defined as time from treatment initiation to demise from any cause or last follow-up. EFS was defined as time from treatment initiation to disease progression or relapse or demise from any cause. Response was assessed by modified Cheson’s lymphoma response evaluation criteria. STATA 13.0 was used to assess survival by Kaplan-Meier analysis and log rank test. Factors affecting survival were assessed by multivariate analysis (Cox proportional hazards model) and expressed as adjusted hazard ratio (aHR). p value < 0.05 defined statistical significance. Results: Median age was sixty years; male-female ratio 3:1. Thirty-five (39.0%) had one or more co-morbidities, 79(88.0%) generalised lymphadenopathy, 72(80.0%) extra-nodal involvement, 49(54.0%) B symptoms, 84(93.0%) advanced stage (III/IV), 49(54.0%) high risk MCL international prognostic index (MIPI). Clinical and tumor characteristics, response rates after initial induction were similar in both maintenance and non-maintenance groups. Overall, 52(58.0%) patients were alive with median follow-up of 63.0 months (inter-quartile range 37.0-90.0 months). Median OS was 37.5 months in non-maintenance group and did not reach in maintenance group. Estimated 1.0-, 2.0, 3.0-year OS were 100.0%, 91.0%, 81.0% vs 75.0%, 63.0%, 55.0% respectively in maintenance vs non-maintenance group. RM was significantly associated with better OS [aHR (95% confidence interval): 0.31 (0.13-0.75), p=0.01]. Advanced stage, Eastern Co-operative Oncology Group performance status (ECOG PS) ≥2 at presentation were also significant factors for poor OS. Median EFS was significantly lower in non-maintenance group [14.0 vs 42.5 months; aHR (95% confidence interval): 0.34 (0.18-0.64), p=0.001]. Advanced stage, anemia, high risk MIPI at presentation were also significant factors for poor EFS. Conclusions: This was the first study from south-east Asia demonstrating impact of rituximab maintenance in MCL. Rituximab maintenance significantly improved OS and EFS of MCL patients.
A phase Ia/Ib, non-randomized, open-label, dose escalation and expansion trial of the B7-H6/CD3 T-cell engager BI 765049 with or without ezabenlimab in Asian patients with advanced solid tumors.
Authors: Doi Toshihiko , Yamamoto Noboru , Kitano Shigehisa , Latek Robert , Hou Jianrui , Tanaka Yuko
Published: July 2024

TPS2669

Background: Bispecific T-cell engagers represent a promising therapeutic approach for patients with solid tumors; however, these agents require an appropriate target antigen. B7-H6 is an encouraging target as it is expressed on multiple solid tumors but shows only limited expression on normal tissue (1). BI 765049 is a novel immunoglobulin G (IgG)-like T-cell engager designed to simultaneously bind B7-H6-expressing tumor cells and CD3 on T-cells resulting in the formation of a cytolytic synapse that triggers apoptosis of the tumor cells. Methods: NCT06091930 is a Phase I, non-randomized, open-label, multi-center, dose escalation and expansion trial that aims to assess the safety and tolerability of BI 765049 alone or in combination with programmed cell death protein 1 inhibitor ezabenlimab, in patients with advanced or unresectable gastric cancer, colorectal cancer (CRC), pancreatic ductal adenocarcinoma, hepatocellular cancer, head and neck squamous cell carcinoma, or non-small cell lung cancer. Patients must have progressed on, or be ineligible for, standard therapies. Key inclusion criteria include confirmed B7-H6 expression (central pathology review) except in CRC; ≥1 evaluable target lesion outside of the central nervous system (Response Evaluation Criteria in Solid Tumors [RECIST] v1.1); and Eastern Cooperative Oncology Group performance status 0/1. Patients with prior B7-H6-targeted treatment are ineligible. The study is divided into four parts: dose escalation and expansion of BI 765049 monotherapy (Parts I and II, respectively), and in combination with ezabenlimab (Parts III and IV, respectively). BI 765049 dose escalation will be guided by a Bayesian logistic regression model with overdose control. Treatment will continue until progressive disease or discontinuation for other reasons, or for up to 36 months. The primary endpoint for Parts I and III is the occurrence of dose-limiting toxicities; and for Parts II and IV it is objective response (OR; determined by the investigator; RECIST v1.1). The secondary endpoints for Parts I and III are pharmacokinetic (PK) parameters and OR (RECIST v1.1); and for Parts II and IV secondary endpoints are progression-free survival, duration of response, disease control, PK measurements, and OR (immunotherapy RECIST [iRECIST]). 1. Zhang W, et al. Clin Cancer Res 2022;28(23):5190–5201. Clinical trial information: NCT06091930 .
Phase 1 study of ASP1002, a bispecific antibody targeting claudin 4 (CLDN4) and CD137, in patients with locally advanced (LA) or metastatic solid tumors that express CLDN4.
Authors: Pelster Meredith , Marron Thomas Urban , Friend Brian D , Fan Alan , Yang Jianning , Spira Alexander I.
Published: July 2024

TPS2670

Background: The lack of benefit for many cancers from newer-generation combination chemotherapies has stimulated research into targeted agents. CLDN4, a claudin protein family member that regulates tight junction formation, is highly expressed in multiple tumor types including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), colorectal cancer (CRC), prostate adenocarcinoma (PA), ovarian cancer (OC), and triple-negative breast cancer (TNBC). Following primary T cell activation, CD137 provides a costimulatory signal that enhances T cell proliferation and cytokine production. Together CLDN4 and CD137 represent promising therapeutic targets for solid tumors. ASP1002 is a bispecific antibody designed to target CLDN4 and CD137, thereby enhancing the antitumor response of T cells against CLDN4-expressing tumor cells. Methods: This phase 1 first-in-human, open-label, multicenter study (NCT05719558) is evaluating the safety and tolerability, maximum tolerated dose (MTD), and/or recommended phase 2 dose (RP2D) of ASP1002 in adult patients with LA or metastatic solid tumors that express CLDN4. The primary endpoint is safety and tolerability, as assessed by dose-limiting toxicities (DLTs), adverse events (AEs), serious AEs, laboratory tests, vital signs, ECGs, PEs, and ECOG performance status. Secondary endpoints are pharmacokinetic characteristics; confirmed objective response rate (ORR), duration of response, and disease control rate per iRECIST and RECIST 1.1; and incidence rate and expression levels of CLDN4 by immunohistochemistry. Dose escalation will include patients with LA or metastatic NSCLC, UC, CRC, PA, OC, or TNBC. ASP1002 will be administered at escalating doses Q1W IV on days 1, 8, 15 in a 21-day cycle until discontinuation to determine MTD and/or candidate RP2D regimens. At doses ≥10 mg, multi-participant cohorts will be included. Safety follow-up visits will occur within 7 days posttreatment, and on 30 and 90 days posttreatment. Next, dose expansion will enroll patients with LA or metastatic NSCLC, UC, CRC, and other tumor types with confirmed complete response (CR) or partial response (PR) in dose escalation. Candidate RP2D regimens based on dose escalation data will be evaluated in ≤40 patients per dose level, per tumor type in dose expansion. ORR (confirmed CR or PR) per iRECIST will be evaluated in tumor-specific expansion cohorts. The minimum number of responders needed to establish activity is 4 (NSCLC), 3 (CRC), and 7 (UC). Study enrollment is currently ongoing in the United States. Clinical trial information: NCT05719558 .
Phase I/II trial of LAVA-1207, a novel bispecific gamma-delta T-cell engager alone, or with low dose IL-2 or pembrolizumab, in metastatic castration resistant prostate cancer (mCRPC).
Authors: Mehra Niven , Voortman Jens , Wise David R , Calvo Emiliano , Piulats Josep M. , Gonzalez-Billalabeitia Enrique , Ortego Ignacio , Swami Umang , Picus Joel , Karlik Meghan , Bihani Teeru , Ruben Jurjen , Macia Sonia , van der Vliet Hans J. , Chaney Marya F. , Robbrecht Debbie
Published: July 2024

TPS2672

Background: LAVA-1207 is a humanized bispecific antibody that binds with high affinity to the Vδ2 chain of Vγ9Vδ2-T cells and to prostate-specific membrane antigen (PSMA). It comprises a heterodimer of two fusion proteins, each consisting of a VHH linked to a human IgG1 Fc domain. Preclinical evidence demonstrates that, upon binding both targets, LAVA-1207 leads to potent Vγ9Vδ2-T cell degranulation and cytolytic activity against PSMA-expressing prostate cancer cells. IL-2 is an immune modulator which has been shown to support expansion of activated Vγ9Vδ2-T cells. PD-1 is an inhibitory immune checkpoint receptor that can dampen (Vγ9Vδ2-) T cell reactivity, suggesting that pembrolizumab could potentiate the effect of LAVA-1207. Methods: This trial is a phase 1/2a open label study with a 3+3 design in patients with refractory mCRPC to assess the safety of LAVA-1207 alone or with low dose IL-2 or with pembrolizumab, and to determine the recommended Phase 2a dose (RP2D). Secondary objectives include evaluation of pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity. Exploratory endpoints include evaluation of the effect of study treatment on circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). LAVA-1207 is administered IV every two weeks. Two parallel cohorts assessing LAVA-1207 with low dose subcutaneous IL-2 have been implemented: (1) single IL-2 administration and (2) three IL-2 administrations on consecutive days per cycle for up to four cycles. An additional dose escalation arm evaluates LAVA-1207 in combination with pembrolizumab, 400mg Q6W, IV. Patients with mCRPC that have failed at least one prior AR therapy and taxane-based chemotherapy (unless deemed medically unsuitable to receive a taxane) will be enrolled on the study. Patients should have progressive disease either by PSA or by RECIST 1.1 or appearance of 2 or more bone metastases. Patients must have ECOG performance status of 0-1. PSMA-PET is performed at baseline. Paired biopsies are requested to further assess LAVA-1207 activity. Dose escalation is ongoing. Expansion arm(s) will be included based on available data from part 1 of the study and may include one or more of LAVA-1207, LAVA-1207 with low dose IL-2, or LAVA-1207 in combination with pembrolizumab. Clinical trial information: NCT05369000 .
The FIPO23 trial: First-in-human phase I/II study of XON7 in advanced solids tumors.
Authors: Bennouna Jaafar , Shneiker Françoise , BLAY Jean Yves , Awada Ahmad , Bassissi Firas , Ratta Raffaele , Delord Jean-Pierre
Published: July 2024

TPS2673

Background: XON7 is a first-in-class glyco-humanized polyclonal antibody (GH-pAb) targeting selectively multiple tumor-associated antigens. XON7 induces tumor cell apoptosis and promotes the elimination of tumor cells by immune effector cells through CDC (Complement Dependent Cytotoxicity) and ADCP (Antibody-Dependent Cell Phagocytosis). XON7 demonstrated anti-tumor efficacy in mice xenograft models with human solid tumors such as colon, prostate, lung and triple negative breast cancers. Safety pharmacology and toxicology studies in non-human primates demonstrated an acceptable safety profile for XON7. Taken together, these preclinical data support the initiation of human trials in patients with advanced solid tumors. Methods: First-in-patient, multicenter, open-label, two phases (dose-escalation (ESC) followed by dose expansion (EXP)) study of XON7 single agent, in patients with relapsed refractory, locally advanced or metastatic solid tumors without standard available treatments ( NCT06154291). Key eligibility criteria include disease progression after ≤ 4 lines of therapy; age > 18 years; ECOG performance status ≤2; adequate organ functions; no known CNS involvement. All advanced or metastatic tumor types except glioblastoma, can be included during ESC. Primary endpoints: safety, tolerability and determination of MTD/RP2D. Secondary endpoints: pharmacokinetics (PK), pharmacodynamics, immunogenicity and preliminary anti-tumor activity (RECIST 1.1). AEs graded according to CTCAE 5.0. In the ESC part, XON7 is administered as 60-min intravenous infusion every 2 weeks according to an escalating schedule of doses from 1.5 to 20 mg/kg for up to 12, 28-day cycles. Dose escalation/de-escalation is based on the Bayesian Optimal Interval (BOIN) design, up to 45 pts are planned. At the recommended dose, up to 7 EXP cohorts (30 pts each) defined according to the primary tumor site are planned. Bayesian sequential monitoring will be used. Patient recruitment is planned or ongoing at 25 sites worldwide. Results: As of Feb 3rd, 2024, 3 pts are enrolled in the first dose cohort and have received XON7 at dose 1,5 mg/kg Q2W for the first 28-days cycle. Conclusions Accrual is ongoing in this first-in-human trial of XON7. Clinical trial information: NCT06154291 .
An open-label, multicenter phase 1 study to characterize safety, tolerability, preliminary antitumor activity, pharmacokinetics, and pharmacodynamics of VIP943 monotherapy in patients with advanced CD123+ hematologic malignancies.
Authors: Strickland Stephen Anthony , Curran Emily K. , Jamy Omer Hassan , Percival Mary-Elizabeth , Johnson Amy J. , Birkett Joseph , Huang Xin , Frigault Melanie M. , Lerchen Hans-georg , Stelte-Ludwig Beatrix , Navarro Tasheda , Peck Jim , Gross Wyatt , Izumi Raquel , Hamdy Ahmed M. , Daver Naval Guastad
Published: July 2024

TPS3167

Background: VIP943 is an anti-CD123 antibody-drug conjugate (ADC) with a unique linker cleaved only by legumain and a novel kinesin spindle protein inhibitor payload. The linker-payload was engineered to increase the therapeutic index thereby improving efficacy and reducing severe toxicities compared with current ADCs. In an in vivo MOLM-13 model, VIP943 had statistically significant (p <0.001) improvement in tumor growth inhibition compared with the only ADC approved for the treatment of acute myeloid leukemia (AML), gemtuzumab ozogamicin (GO). In a nonhuman primate (NHP) single dose toxicology study, VIP943 (20 mg/kg) showed no signs of toxicity as measured by hematology, serum chemistry and survival. In contrast, NHP treated with a single dose of GO (3 mg/kg) had significant toxicity including death and mandatory euthanasia. The single-dose toxicity of GO was ameliorated by substituting the VIP943 proprietary linker and payload on an anti-CD33 antibody (3 mg/kg) as measured by hematology, serum chemistry and survival. (1,2). Methods: This trial in progress (NCT06034275) is an open-label, multicenter, Phase 1, first-in-human (FIH), dose-escalation and dose-optimization study of VIP943 in subjects with relapsed or refractory CD123+ hematologic malignancies including AML, myelodysplastic syndrome, and B-cell acute lymphoblastic leukemia. A cycle of VIP943 treatment is 28 days of once weekly intravenous infusions with no pause between cycles. The dose-escalation portion of this study follows a standard 3+3 design. Dose escalation decisions will be made by the safety review committee, and decisions will be based on the incidence of dose-limiting toxicities (DLTs). Based on FDA guidance, a dose-optimization portion of this study will randomize subjects into ≥2 dose cohorts to derive a recommended dose range for Phase 2. The study will also characterize the pharmacokinetics of VIP943 and its components and explore potential biologic activity by assessing pharmacodynamic/exploratory biomarkers, and antitumor activity using standard response criteria. As this is a FIH study, only subjects with CD123+ hematologic malignancies who have exhausted all available therapies or are not fit for standard of care can be enrolled. The results from this study will form the basis for decisions for future studies. Enrollment for cohorts 1 (no DLTs) and 2 (safety review ongoing) has completed. 1. Stelte-Ludwig et al ASH 2022. 2. Stelte-Ludwig et al ASH 2023. Clinical trial information: NCT06034275 .
On Bangtan Remixed: A Critical BTS Reader
Authors: Ahn Patty , Cho Michelle , Gonzalez Vernadette Vicuña , Neutill Rani , Nguyen Mimi Thi , Wong Yutian
Published: July 2024

The volume’s introduction begins by presenting and describing the K-Pop idol group BTS, their performance styles, and the multiplicity of their stage, screen, and “real life” identities. Situating their emergence as the world’s preeminent K-pop musical group, the introduction discusses the roots and musical traditions that have shaped the emergence of K-Pop and BTS’s place in the idol pantheon. It provides historical context for the development of youth culture in South Korea that coincides and fuels the rise of Hallyu, or the Korean Wave. The introduction also tracks the development of the K-Pop idol system and industry practices, including its roots in Japan. The introduction also contextualizes the issues of race and anti-Blackness in K-Pop within a complex regional colonial history and South Korea’s fraught relationship with the United States. Finally, the introduction provides an overview of the book’s structure and contents.
Tradition, Transition, and Trends: Contextualizing BTS's Gugak-Inspired Performance of “IDOL”
Authors: Lee Wonseok
Published: July 2024

Wonseok Lee’s “Tradition, Transition, and Trends: Contextualizing BTS’s Gugak-Inspired Performance of ‘IDOL’” looks at the state’s role in K-Pop’s integration of traditional Korean music and dance. In 2009, the government established an agency affiliated with the Ministry of Culture, Sports, and Tourism, called KOCCA (the Korea Creative Content Agency), which has initiated several projects to support local musicians, including idol groups, independent musicians, solo artists, and even traditional Korean music gugak-oriented fusion bands. Lee claims that the government contributes to not only expanding the musical boundaries of K-Pop but also diluting a musical boundary between gugak and popular music by supporting various kinds of musicians. Using BTS’s performance of “IDOL” at the 2018 Melon Music Awards, Lee demonstrates how incorporating elements of Korean traditional music and dance cultures are a significant part of the band’s global success story and reflects broader trends of cultural promotion within the K-Pop industry.
Hustlin’ until Dope: How BTS's Rap Line Cultivated Their Hip-Hop Identities
Authors: Parham Nykeah
Published: July 2024

In “Hustlin’ Until Dope: How BTS’s Rap Line Cultivated Their Hip-Hop Identities,” Nykeah Parham highlights the US hip-hop genealogy from which BTS draws. Originally debuted as a hip-hop group, BTS’s roots in rap and hip hop stood in stark contrast at the time to the flash of the K-Pop idol world. Parham provides contextualized close readings of the Rap Line’s cyphers and solo mixtapes to trace their education and investment in hip-hop culture and to track their engagement with the social, cultural, and historical roots of hip hop as a specifically African American genre. As the primary songwriters of the group, RM, SUGA, and j-hope’s in-depth engagement with hip-hop traditions and styles have shaped BTS’s musical identity at the intersection of hip hop and Korean popular music.
“Life Goes On”: Social and Musical Space in BTS's Midpandemic Album BE
Authors: Piccialli Stefania
Published: July 2024

In “‘Life Goes On’: Social and Musical Space in BTS’s Midpandemic Album BE,” Stefania Piccialli analyzes the band’s 2020 album, released at the height of the COVID-19 pandemic, during which the band’s activities—especially their MAP OF THE SOUL TOUR—were canceled or postponed. In this meditation on the spatiality of isolation and loneliness, she considers the aesthetic of the album’s promotion and packaging as well as its musical and lyrical messages as a deliberate embrace across what felt like insurmountable distance. From the promotional photos featuring individual rooms curated by each member, to the songs identifying music as a place of strength and safety in the face of a pandemic (i.e., “Life Goes On”), and the physical design of the album itself, BE distinguishes itself as a quarantine album and provides an elaboration on spatiality and connection during the unprecedented COVID-19 times.
Blood, Sweat, and Tears: BTS, Bruegel, and the Baroque
Authors: Kwon Marci
Published: July 2024

In her chapter, “Blood, Sweat, and Tears: BTS, Bruegel, and the Baroque,” Marci Kwon reads the music video for “Blood, Sweat & Tears” through the lens of European art history, examining how the canon of Renaissance and Baroque art provide a visual language to invoke the band members’ exploration of art and life. The chapter unfolds with a significant visual component that connects the visual elements—costuming, sets, lighting–of the music video with various reference works from the canon. The chapter asks about what works of art say about an artist and vice versa. She argues that as artists themselves, BTS turns to aesthetic histories to reflect on the categories of the real or authentic that are often brought to bear upon the group.
The Platformization of K-Pop: From Weverse to NFTs
Authors: Jin Dal Yong
Published: July 2024

With the rapid growth of digital technologies, K-Pop has been at the center of the Korean cultural industries in the early 21st century. K-Pop continues to be a frontier of digital platforms and entertainment agencies that utilize digital technologies to advance new forms of cultural production. Indeed, K-Pop has been more deeply connected to digital platforms than any other cultural genre. In “The Platformization of K-Pop: From Weverse to NFTs,” Dal Yong Jin outlines how emergent media platforms drove shifts in the marketing and distribution of music, the facilitation of interactions between K-Pop idols and fans on social media, and the innovation of new forms of digital performance and art. The author looks at the case study of BTS to track how these new forms have developed.
“Black Guy Reacts to BTS for the First Time”: Provocations from a Black ARMY
Authors: Brown Jheanelle
Published: July 2024

In her personal essay “‘Black Guy Reacts to BTS for the First Time’: Provocations from a Black ARMY,” Jheanelle Brown examines another form of fan-created transmedia–the reaction video. In the past decade, YouTube reaction videos have become a popular mode of fan production. For those versed in YouTube, “Black guy reacts to BTS for the first time” is a tried-and-true method for gaining followers and creating buzz around a channel because of the strength and commitment of BTS’s fandom, ARMY. Videos such as these have a built-in audience and guaranteed response. Recognizing that BTS does not lean on performative Blackness through gesture, AAVE (African American Vernacular English), or dress, while at the same time being critically aware of BTS’s debt to Black music, Brown explores how reaction videos made by cis-hetero Black men might provide a space for validation, solace, and dialogue about race, authenticity, and aesthetics.
Jung Kook's Button, or the GIF That Keeps on Giving
Authors: Nguyen Mimi Thi
Published: July 2024

Mimi Thi Nguyen turns to fan-made animated GIFs fixating on the singular moment of Jung Kook’s button coming undone during a performance. Turning to the erotic possibilities of this looping instance of uncalculated flesh, in “Jung Kook’s Button, or the GIF that Keeps on Giving,” she examines the communal desire captured in this repetitious striptease to highlight the pleasure of the obsessive return and anticipation of the GIF. Without temporal unfolding—or full undressing—these animated GIFs specialize in selective movements that give life to desire through the anticipation of what is already to come again. That such desire is also communal, while asynchronous, is all the more striking. It is as such that these fan-generated temporal loops also express something significant about the forms of perpetual singularity found in the moment, the detail, the fragment –at which BTS excels in generating, endlessly—that demand the constancy of our attention.
Dyslipidemia among psychiatric patients with depression – common possible reasons and treatment implications – review
Authors: Pleska Kacper , Wojtania Joanna , Łepik Michał , Uszok Zofia , Rosiak Krzysztof , Reguła Kacper , Waloch Kamil , Piaszczyński Szymon , Czajka Andrzej , Szymański Bartłomiej
Published: July 2024

Dyslipidemia is a medical term used to describe an abnormal level of lipids (fats) in the blood. This can include elevated levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high density protein lipoprotein (HDL) cholesterol and serum triglicerides. Depression, also known as depressive disorder, is a common mental illness. It is characterized by a persistent feeling of sadness, loss of pleasure, or lack of interest in activities that are present of at least two weeks and significantly impair patient everyday functioning. Dyslipidemia and depression can co-occur due to a complex interplay of shared risk factors, such as inflammation, metabolic syndrome, medication side effects, and lifestyle changes, suggesting a bidirectional relationship where each condition might contribute to the development or exacerbation of the other.
Given these considerations, a comprehensive approach to managing dyslipidemia in psychiatric patients with depression is essential. This should include regular monitoring of lipid profiles and monitoring of anticholesterol and antidepressant drugs. Interestingly, simple lifestyle changes, such as a healthy diet and exercise, have an impact on the treatment of depression and dyslipidemia.
La transformación mediática internacional de Atapuerca: de Nature a la prensa de referencia.
Authors: Fernandez Muerza Alex
Published: July 2024

Este trabajo investiga la transformación mediática internacional de Atapuerca gracias a los descubrimientos paleontológicos publicados por sus investigadores en Nature. Para ello, se analizaron dos noticias en 1993 y 1999, a partir de los envíos de artículos publicados en dicha revista científica británica, y cómo se trasladaron a la prensa de referencia –medios caracterizados por su calidad e influencia social– nacional e internacional. En concreto, se realizó un análisis de contenido de dichas noticias en El País y La Vanguardia como diarios nacionales; y Le Monde (Francia), The Times (Reino Unido) y The New York Times (Estados Unidos) como internacionales. El trabajo concluye que Atapuerca como marca mediática tuvo su punto de inflexión en 1993, se consolidó y amplió en 1999, y su alcance fue más bien nacional. Para ello, Nature fue esencial, pero también provocó una servidumbre comunicativa que retrasó su aparición mediática, privando a la sociedad de un conocimiento científico financiado con fondos públicos. Además, confirma lo señalado por estudios previos sobre la importancia de los periodistas científicos para la producción de noticias de ciencia de calidad.
A Study of Hospital Competition in Yogyakarta City with Huff’s Gravity Model and Valuation Methods
Authors: Vieira Isabel , Asmara Gea Dwi
Published: July 2024

This analysis was conducted to identify the level of hospital competition in Yogyakarta City. The object of this study is 12 hospitals in Yogyakarta City. The analytical tools in this study consist of two methods. The ?irst method is the Huff’s Gravity Model used to estimate the probability of visits to each hospital so that the competition between hospitals can be known. The second method is the valuation method using the income approach to calculate the potential value of the hospital. The results of this study show that the largest visit probability and potential value are owned by RS PKU Muhammadiyah Yogyakarta with a probability value of 19.91% and a potential value of IDR 8,493,747,933,578 for an optimistic estimate, IDR 3,370,534,894,277 for a moderate estimate, and IDR 1,400,068,340,700 pessimistic estimate. The contribution of this research can be considered in making investment decisions, especially in planning the establishment of a new hospital or expanding the capacity of an existing hospital. For investors who will invest in the hospital industry, they should look for locations that are easily accessible and avoid building hospitals with lower types near hospitals with high types; this will affect the level of probability of visits to the hospital itself. If the level of visit opportunity is low, then the potential value that will be obtained will also be low.
Do Household Consumption and Literacy Rate Impact the Fluctuation of the Unemployment in Indonesia?
Authors: Sunni Muhammad Ismail , Wanof M. Indre , Wijaya Angga Kusuma
Published: July 2024

This paper aims to investigate the linkage and explore what has determined the unemployment rate in Indonesia from 2000 to 2021 which include literacy rate, school enrolment, labour force participation and household and non-profit institutions serving households (NPISHs) as the main explanatory variables. To control factors of unemployment and avoid spurious or misleading results, other than FDI, we include other macroeconomics variables such inflation, trade and interest rate. This study deploys timeseries regression and Ordinary Least Square (OLS) as the regression technique to estimate the coefficients of the linear function that best fits the data. To assess the model's assumptions and diagnose any potential issues that may affect the model's reliability and validity, the author applied heteroscedasticity, normality, multicollinearity, and autocorrelation test. All data are attained from World Development Index (WDI). Overall, HNC is the only determinant significantly increase level of Indonesia unemployment. While the increase of FDI may exacerbate Indonesia’s unemployment rate, LFP plays significant role in reducing the unemployment rate in Indonesia. The contribution of this paper lies in providing a nuanced understanding of the specific determinants of unemployment, with a particular emphasis on the significant impact of NPISHs. Based on the findings, policymakers should think about making investments in NPISHs to spur growth in the economy while generating job opportunities.