bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 1 study of SGN-BB228, an investigational CD228 x 4-1BB costimulatory antibody anticalin bispecific, in patients with advanced melanoma and other solid tumors (SGNBB228-001).
Authors: Henry Jason Timothy , Mehnert Janice M. , Rudnicki Erika , Pinelli Juan , Daud Adil 
Published: June 2023

TPS9597 Background: SGN-BB228 is an investigational costimulatory Antibody Anticalin bispecific (Mabcalin) molecule directed to CD228 and 4-1BB. CD228 is a tumor-associated antigen selectively expressed by multiple tumor types including melanoma, mesothelioma, pancreatic, colorectal, and lung cancers with minimal expression in normal tissue. 4-1BB is an inducible costimulatory receptor expressed on activated T cells and other immune cell populations. The clinical development of 4-1BB agonist antibodies has been hampered by limited efficacy and/or poor tolerability at active doses (Segal et al 2017, Segal et al 2018). SGN-BB228 is designed to deliver a potent costimulatory bridge between tumor-specific T cells and tumor cells, potentially localizing antitumor activity to the tumor microenvironment and expanding the therapeutic window for 4-1BB agonism. In vitro, SGN-BB228 shows potent CD228-conditional 4-1BB stimulation and cytotoxic T cell activation (Updegraff et al 2022) providing rationale for evaluating SGN-BB228 in patients (pts) with melanoma or other solid tumors. Methods: SGNBB228-001 (NCT05571839) is a phase 1, open label, multicenter study designed to evaluate the safety, tolerability, PK, and antitumor activity of SGN-BB228 in adults ≥18 years of age with advanced melanoma or other solid tumors. The study includes dose escalation (Part A), dose and schedule optimization (Part B; optional), and dose expansion in disease-specific cohorts (Part C). Parts A and B will enroll pts with histologically or cytologically confirmed metastatic or unresectable cutaneous melanoma, and Part C will enroll pts with cutaneous melanoma, mesothelioma, pancreatic, colorectal, or non-small cell lung cancer. Pts must have disease that is relapsed, refractory, or intolerant to standard of care therapies, ECOG PS 0-1, and adequate organ function. Pts with known active CNS metastases or prior use of agents targeting CD228 or 4-1BB are excluded. Pts with cutaneous melanoma must have received anti PD(L)-1 agent as monotherapy or in combination. Pts with a targetable BRAF mutation must have received, been intolerant to, or declined treatment with BRAF/MEK targeted therapy prior to study entry. Primary endpoints include rate of adverse events, laboratory abnormalities, dose-limiting toxicities, and cumulative dose-level safety. Secondary endpoints are PK, ORR, DOR, PFS, OS, and incidence of antidrug antibodies. Safety and antitumor activity endpoints will be assessed by dose, schedule, and tumor type using descriptive statistics. The ORR and its 95% CI will be estimated. DOR, PFS, and OS will be estimated using Kaplan-Meier method. Enrollment is ongoing in the US and planned in Europe. Clinical trial information: NCT05571839 .
A phase 3 trial of fianlimab (anti–LAG-3) plus cemiplimab (anti–PD-1) versus pembrolizumab in patients with previously untreated unresectable locally advanced or metastatic melanoma.
Authors: Baramidze Ana , Gogishvili Miranda , Makharadze Tamta , Zhvania Mariam , Vacharadze Khatuna , Crown John , Melkadze Tamar , Hamid Omid , Long Georgina V. , Robert Caroline , Sznol Mario , Martinez-Said Hector , Mani Jayakumar , Chaudhry Usman , Salvati Mark , Lowy Israel , Fury Matthew G. , Gullo Giuseppe 
Published: June 2023

TPS9602 Background: Fianlimab (anti-lymphocyte activation gene 3 [LAG-3]) and cemiplimab (anti- programmed cell death-1 [PD-1]) are both high-affinity, fully human, IgG4 monoclonal antibodies (Abs). Concurrent blockade of anti-LAG-3 and anti-PD-1 has shown enhanced efficacy (increase in progression free survival [PFS]) in advanced melanoma (Mel). We previously presented data from a phase 1 study showing a 63.8% objective response rate (ORR) across two separate cohorts of advanced PD-(L)1 naïve metastatic Mel patients (pts) treated with fianlimab plus cemiplimab with an acceptable risk-benefit profile. Methods: This is a randomized, double-blind, phase 3 study to evaluate fianlimab plus cemiplimab compared to pembrolizumab in pts with previously untreated unresectable locally advanced or metastatic Mel (NCT05352672). This study will be conducted globally, at approximately 200 sites. Key inclusion criteria are: (1) ≥12 years of age; (2) histologically confirmed unresectable Stage III and Stage IV (metastatic) Mel (3) no prior systemic therapy for advanced unresectable disease, prior (neo)adjuvant therapies are allowed with treatment/disease-free interval of 6 months; (4) measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1; (5) valid LAG-3 results; (6) Eastern Cooperative Oncology Group performance status (PS) of 0 or 1 (for adult pts), Karnofsky PS ≥70 (pts ≥16 years) or Lansky PS ≥70 (pts < 16 years); and (7) anticipated life expectancy of at least 3 months. There are 4 arms to the study: (1) Arm A: fianlimab (1600 mg) + cemiplimab (350 mg) every 3 weeks (Q3W), intravenously (IV); (2) Arm A1: fianlimab (400 mg) + cemiplimab (350 mg) Q3W, IV; (3) Arm B: pembrolizumab (200 mg Q3W, IV) + saline/dextrose placebo (placebo); (4) Arm C: cemiplimab (350 mg Q3W, IV) + placebo. The trial is expected to enroll approximately 1590 pts. The primary endpoint is progression-free survival. The key secondary endpoints are overall survival and objective response rate. The additional secondary endpoints include disease control rate, duration of response, safety, pharmacokinetics of cemiplimab and fianlimab, and immunogenicity (incidence and titer of anti-drug Abs and neutralizing Abs). The study is currently open for enrollment. Clinical trial information: NCT05352672 .
A pilot, open study to assess efficacy and safety of ON-01910 (rigosertib) in patients with recessive dystrophic epidermolysis bullosa associated locally advanced/metastatic squamous cell carcinoma.
Authors: Banner Lauren , Hosler Linda , Parris Matthew , Gelder Mark Stephen , Laimer Martin , Bauer Johann , South Andrew , Nikbakht Neda 
Published: June 2023

TPS9604 Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is an extremely rare, severe blistering disease driven by mutations in collagen seven (COL7A1). Besides the skin and mucosal blistering, this genodermatosis is also characterized by aggressive cutaneous squamous cell carcinomas (cSCCs) arising from patients’ chronic wounds. The cumulative risk of death from these cSCCs is 70% by age 45. There are limited effective treatment options for advanced (unresectable/metastatic) RDEB-associated cSCCs. While the standard of care for any advanced cSCC is immune checkpoint inhibitors, only half of the treated patients had responses in clinical trials. Their use for RDEB-associated SCCs been limited to case reports, and our own experience has not been positive. Conventional chemotherapy in RDEB-associated cSCC is another proposed treatment strategy, however, case reports demonstrated limited response rates without lasting effects. Currently it is recommended palliatively, although there are concerns about adverse effects. Other existing options are tyrosine kinase inhibitors, resulting in mixed responses to treatment for advanced cSCCs of any type, and epidermal growth factor receptor inhibitors, demonstrating limited effectiveness in a small number of case reports on RDEB-associated cSCCs. More effective therapeutic modalities for advanced/metastatic RDEB-associated cSCCs are needed. We previously demonstrated that RDEB SCC keratinocytes are specifically affected by polo-like kinase-1 (PLK-1) siRNA. Eight PLK-1 inhibitors were screened for cytotoxicity. Of the 8 candidates, ON-01910 was superior as it demonstrated the largest therapeutic window for distinguishing between tumor versus normal cells. The ON-01910 clinical trial is in progress in patients with RDEB with advanced/metastatic cSCCs. Methods: ON-01910 is being evaluated in both oral and intravenous formulations in an open-label, non-randomized phase 2 study in RDEB patients with advanced, treatment resistant cSCC. The trial explores the anti-tumor activity of ON-01910 and evaluates its safety and tolerability. Secondary objectives are to assess the impact on quality of life and to perform biomarker analysis on patient tissue. This study began in August 2021 and is ongoing. One patient is currently enrolled in the oral arm at Thomas Jefferson University in the USA. Safety is assessed according to the CTCAE v5. Tumor response in lymph nodes is determined per the RECIST 1.1 and in skin via clinical examination with serial tumor measurements. Key eligibility criteria include 1) diagnosis of RDEB and associated measurable, advanced cSCC confirmed histologically 2) failure to respond to standard of care including excision for localized disease 3) no concomitant cancer therapies. Clinical trial information: NCT04177498 .
KEYVIBE-010: Adjuvant coformulated vibostolimab with pembrolizumab versus adjuvant pembrolizumab in patients with high-risk stage II-IV melanoma.
Authors: Long Georgina V. , Eggermont Alexander M. , Gershenwald Jeffrey E. , Schadendorf Dirk , Ascierto Paolo Antonio , Dummer Reinhard , Hauschild Axel , Carlino Matteo S. , Ribas Antoni , Robert Caroline , Scolyer Richard A. , Sondak Vernon K. , Cohen Jonathan E , Zhang Jinchun , Grebennik Dmitri O. , Krepler Clemens , Luke Jason J. 
Published: June 2023

TPS9611 Background: Pembrolizumab is an anti−PD-1 monoclonal antibody that has been shown to significantly improve recurrence-free survival and distant metastasis-free survival when used as adjuvant therapy in patients with high-risk resected melanoma (Long GV, et al. Lancet Oncol. 2022;23:1378-88; Eggermont AMM, et al. Lancet Oncol. 2021;22:643-54). Combining pembrolizumab with other therapies may further improve outcomes in this setting. Vibostolimab is an anti-TIGIT monoclonal antibody that showed antitumor activity and manageable safety when used in combination with pembrolizumab in patients with advanced solid tumors in the phase 1 KEYVIBE-001 study (Niu J, et al. Ann Oncol. 2022;33:169-80). The randomized, double-blind, phase 3 KEYVIBE-010 study (NCT05665595) is designed to evaluate the efficacy and safety of adjuvant coformulated vibostolimab and pembrolizumab (MK-7684A) versus pembrolizumab alone in patients with resected high-risk stage IIB-IV melanoma. Methods: Eligible patients are ≥12 years of age (weighing ≥40 kg if < 18 years), with surgically resected stage IIB or IIC (pathologic or clinical), III, or IV cutaneous melanoma per AJCC 8th edition guidelines, and an Eastern Cooperative Oncology Group performance status of 0 or 1 (Lansky play-performance scale ≥70 if < 16 years; Karnofsky performance status ≥70 if ≥16 to < 18 years). Patients must not have received any prior systemic therapy beyond complete resection and no more than 12 weeks can have elapsed between final surgical resection and randomization. Patients with ocular, mucosal, or conjunctival melanoma, and prior allogeneic tissue/solid organ transplant are excluded. Patients will be stratified by risk. Approximately 1560 patients will be randomly assigned 1:1 to receive intravenous coformulated vibostolimab 200 mg with pembrolizumab 200 mg or pembrolizumab 200 mg (2 mg/kg up to a maximum of 200 mg for adolescents) every 3 weeks. Treatment will continue for 17 cycles or until disease recurrence, unacceptable toxicity, or withdrawal. The primary end point is recurrence-free survival by investigator review. Secondary end points are distant metastasis-free survival by investigator review, overall survival, safety and tolerability, and quality of life. Hazard ratios and 95% confidence intervals will be estimated using a stratified Cox regression model with the Efron method of handling ties, with treatment as a covariate. Between-treatment differences will be evaluated using a stratified log-rank test. Enrollment is ongoing. Clinical trial information: NCT05665595 .
NADOM trial: Neoadjuvant/adjuvant trial of darovasertib in ocular melanoma (OM).
Authors: O'day Roderick , Conway Max , Lim Li-Anne , McKenzie John , Atkinson Victoria , Glasson William , McGrath Lindsay , Cherepanoff Svetlana , Gray Elin , Maurer Matthew A. , O'Quigley Michael , Shackleton Mark J. , Joshua Anthony M. 
Published: June 2023

TPS9612 Background: Darovasertib (Daro) is a novel inhibitor of PKC, that has pre-clinical activity in GNAQ/GNA11 tumours including ocular melanoma. A recently completed clinical trial of Daro monotherapy in metastatic OM with a response rate of 11%, and DCR of 78% with only mild manageable toxicity, suggesting utility in localized disease and in the adjuvant setting. Methods: NADOM is an investigator-initiated window-of-opportunity phase 2 clinical trial open in 3 centers across Australia. Eligible patients include patients planned for enucleation, ECOG 0-1 with adequate organ function. The primary objective is the feasibility and safety of neoadjuvant Daro in a pilot cohort of 12 patients. Secondary objectives include the effect of Daro on circulating biomarkers (including CTCs and ctDNA), imaging assessments (MRI, FDG-PET and ocular ultrasound), pharmacokinetic and pharmacodynamic correlates and radiographic PFS in the adjuvant setting. Treatment comprises a neo-adjuvant period of treatment of up to 6 months at ophthalmologist discretion with Daro (300mg bid) before definitive management. Patients who demonstrated radiological, biomarker or clinical response are then offered an adjuvant period of treatment for up to 6 months following integrated consensus at multi-disciplinary ocular oncology meetings. DSMB meetings are scheduled to ensure clinical and peri-operative safety regularly. Enrolment commenced in November 2022 and accrual is ongoing in the 6 month neo-adjuvant cohort. Results: To date, an initial safety cohort of 1 month of neo-adjuvant treatment has been cleared following DSMB review. Conclusions: Recruitment is ongoing and expected to complete in late 2023. Clinical trial information: NCT05187884 .
CemiplimAb-rwlc survivorship and epidemiology (CASE): A prospective study of safety and efficacy of cemiplimab in patients with advanced basal cell carcinoma in a real-world setting.
Authors: Park Soo J , Ellison David , Weight Ryan Michael , Homsi Jade , Rabinowits Guilherme , Ruiz Emily S. , Strasswimmer John , Simmons Josh David , Panella Timothy J. , Quek Ruben GW , Ursino Gregory , Pouliot Jean-Francois , Khushalani Nikhil I. 
Published: June 2023

TPS9614 Background: Basal cell carcinoma (BCC) is the most common form of non-melanoma skin cancer in the United States. Surgical excision is the standard treatment, with < 1% of cases progressing to locally advanced or metastatic disease. Hedgehog pathway inhibitors (HHIs) are the first-line therapy for advanced BCC (aBCC); the US Food and Drug Administration and European Medicines Agency have approved the use of cemiplimab (a programmed cell death-1 inhibitor) in advanced BCC (aBCC) patients previously treated with (or are inappropriate for) HHI. Limited real-world data exist on the clinical characteristics, disease management and progression, and survivorship of patients with aBCC. The ongoing C.A.S.E. study aims to evaluate the efficacy, safety, disease evolution, survivorship, and patient reported outcomes (PRO) in patients treated with cemiplimab in the real-world setting. Methods: This trial in progress (NCT03836105) aims to describe the effectiveness and safety of cemiplimab 350 mg administered every 3 weeks for treatment of patients with aBCC in real-world clinical settings. Up to 100 adult patients with aBCC who are prescribed commercially available cemiplimab from ~65 study sites in the United States will be included. The duration of follow-up will be 24 months. Endpoints for this study relate to real-world efficacy, including overall survival; progression-free survival; objective response rate, (partial or complete response); and disease control rate, defined as the percentage who do not progress for ≥ 6 months; Time to response, duration of response, time to treatment failure, and disease-specific death will also be assessed. Real-world safety outcomes will also be captured, including immune-related adverse events, infusion-related reactions, and serious adverse events. Patient selection criteria and treatment patterns will be analyzed using descriptive statistics. This study also aims to describe the patient experience of real-world treatment with cemiplimab. PROs including global quality of life, functioning, and symptoms will be captured at baseline and follow-up visits via the EORTC QLQ-C30 and the Skin Care Index. Recruitment for this trial is ongoing. Clinical trial information: NCT03836105 .
The Assistive Technology for Teaching and Learning of Social Skills for Autism Spectrum Disorder Children: Multimedia Interactive Social Skills Module Application
Authors: Ibrahim Zuraida , Mohamed Juliana , Kassim Noordiana , Bahrudin Ida Aryanie 
Published: June 2023

<p style="text-align: justify;">An earlier study found that assistive technology based on mobile applications significantly improved how social skills were taught to and learned by autism spectrum disorder (ASD) children. Nevertheless, the content of the existing mobile applications is inadequate for capturing the diversity of Malaysian culture, making it unacceptable for local use. Considering cultural norms is a factor in developing social skills in ASD children. It is therefore necessary to develop new assistive technology based on mobile applications that consider Malaysian cultural norms. As a result, the Multimedia Interactive Social Skills Module (MISSM) application was created based on the Addie Model, which offers a systematic process for assisting in developing successful instructional material by fusing instructional theory with learning theory. The MISSM application is based on Malaysia's current social skills curriculum, which helps ASD children become socially competent. Hopefully, it will help them develop better social skills and achieve academically. Finally, local culture-sensitive material for assistive technology based on mobile applications would support Malaysia's adoption of a technology-based teaching and learning strategy and contribute to a better understanding of social skills.</p>
Design of an algorithm for the detection of intravenous fluid contamination in clinical laboratory samples
Authors: Rios Campillo Cristian , Sanz de Pedro Maria , Iturzaeta Jose Manuel , Qasem Ana Laila , Alcaide Maria Jose , Fernandez-Puntero Belen , Rioja Rubén Gómez 
Published: June 2023

Abstract

Objectives
Contamination of blood samples from patients receiving intravenous fluids is a common error with potential risk to the patient. Algorithms based on the presence of aberrant results have been described but have the limitation that not all infusion fluids have the same composition. Our objective is to develop an algorithm based on the detection of the dilution observed on the analytes not usually included in infusion fluids.

Methods
A group of 89 cases was selected from samples flagged as contaminated. Contamination was confirmed by reviewing the clinical history and comparing the results with previous and subsequent samples. A control group with similar characteristics was selected. Eleven common biochemical parameters not usually included in infusion fluids and with low intraindividual variability were selected. The dilution in relation to the immediate previous results was calculated for each analyte and a global indicator, defined as the percentage of analytes with significant dilution, was calculated. ROC curves were used to define the cut-off points.

Results
A cut-off point of 20 % of dilutional effect requiring also a 60 % dilutional ratio achieved a high specificity (95 % CI 91–98 %) with an adequate sensitivity (64 % CI 54–74 %). The Area Under Curve obtained was 0.867 (95 % CI 0.819–0.915).

Conclusions
Our algorithm based on the global dilutional effect presents a similar sensitivity but greater specificity than the systems based on alarming results. The implementation of this algorithm in the laboratory information systems may facilitate the automated detection of contaminated samples.
Decentering the Human in Practical Theologies of Care: An EARTH Method
Authors: Sanders Cody J. 
Published: June 2023

Abstract
This article addresses the problem of human supremacy in the methods of practical theology. It puts forth a practical theological method for experimentation shaped around five interpenetrating dimensions: Ecological, Anthropological, Relational, Technological, and Health/Harm/Healing (the EARTH method). The anticipated outcome of this method is the construction of practical theological projects that aim toward practices of care that continue to address concerns of the human, but always and only as the human is understood to be inextricably situated in an expansive cosmic web of entanglement.
Empowerment and Transformation: Correlating John of the Cross and Judith Herman for Trauma Healing
Authors: DuBois Heather M. 
Published: June 2023

Abstract
The Christian spiritual practice of John of the Cross and the trauma recovery practice of Judith Herman both employ relational theories of healing change. This is a constructive claim that aims to facilitate greater communication between religious and secular approaches to trauma. It is demonstrated through emphases on two dynamics that can increase knowledge and love of self and others, namely empowerment and a three-fold, open-ended process of transformation. Correlating John’s collected works and Herman’s classic Trauma and Recovery, this essay gathers wisdom for healing vulnerable relational selves.
For the Sake of the Church
Authors: Schaeffer Hans , de Muynck Bram , Pleizier Theo , Kater Maarten 
Published: June 2023

Abstract
In this article practical theologians from three Dutch Protestant institutions reflect on developments in the field. Their institutions started as ministry training centers and still have a strong focus on ecclesial practices. This focus has been reinforced by international trends in Practical Theology, mainly by a gradual shift towards an empirical way of working, with an emphasis on participative methods and ethnography. However, the field in the Netherlands continues to have a strong connection with church history and systematic theology. The authors discern three themes that characterize their institutes’ contribution to the international conversation on PT: the divine action within the practices, God’s promises in the context of his covenant, and a realistic view of brokenness, sin, and failure.
THE ENERGY EFFICIENT CONVERTER UNIT WITH FILTERING OF THE HARMONICS OF THE OUTPUT VOLTAGE TRACTION POWER SUPPLY SYSTEM OF DC WITH VOLTAGE OF 3 KV
Authors: Samsonkin V. M. , Panasenko M. V. , Bozhko V. V. , Honcharov Yu. P. , Yeresko O. V. , Zamaruiev V. V. , Liubych R. I. , Sychenko V. H. 
Published: June 2023

The combined system of active filtration of target voltage of the rectifier using an added voltage converter as an in-series link and a high-frequency current inverter as parallel one is offered. Its application allows reducing weight of a choke of the passive filter.