Explore the vast range of titles available.

Abstract Background The Hispanic and Latinx population comprises over 60 million individuals in the United States, representing approximately 18 percent of the total population. Cancer is the leading cause of death in this group. Despite the disease burden, Latinx individuals remain underrepresented in cancer clinical trials, accounting for only 2.3 to 3.9 percent of participants in therapeutic studies. This disparity limits the applicability of research findings and contributes to inequities in outcomes. Barriers such as limited awareness, language discordance, mistrust in the medical system, and structural inequities impact participation. Culturally tailored educational interventions may help address these gaps. This investigator-initiated trial aims to investigate whether a brief, bilingual educational video can improve willingness to participate in clinical trials among Latinx adults diagnosed with genitourinary (GU) malignancies. Methods This is investigator-initiated, randomized, controlled, multi-center trial conducted. Eligible participants are adults aged 18 or older with a histologically confirmed diagnosis of a GU malignancy, including prostate, bladder, kidney, testicular, or penile cancer, or with tumor markers consistent with metastatic germ cell neoplasia. All participants must speak either English or Spanish and be attending their first consultation in Medical Oncology, Radiation Oncology, or Urology. Patients are randomized in a 1 to 1 ratio to either the experimental or control arm (Figure 1). Randomization is stratified by cancer type (prostate versus non-prostate) and language preference (English versus Spanish) to ensure balance across key variables. In the experimental arm, participants watch a 10-minute culturally adapted video in their preferred language. The video was developed in collaboration with clinicians, patient advocates, and community partners. It explains the purpose, risks, and benefits of clinical trials, emphasizes ethical protections, and highlights the importance of Latinx representation in research. Immediately afterward, participants complete the 31-item Attitudes and Intention to Enroll in Therapeutic Clinical Trials (AIET) questionnaire. This validated tool assesses willingness to participate in trials and explores attitudes across six domains, including fear, mistrust, privacy concerns, and knowledge gaps. In the control arm, participants complete the AIET questionnaire without viewing the video. After the survey, they are offered the opportunity to watch the video to ensure equitable access to educational content. The primary endpoint is the proportion of Latinx participants who express willingness to participate in a clinical trial, based on responses to item 31 of the AIET questionnaire. Based on prior data, a baseline willingness of 15 percent is assumed. The study is powered to detect an increase to 35 percent with a sample size of 110 participants (55 per arm), using a one-sided alpha of 0.1 and 80 percent power. Secondary endpoints include the proportion of Latinx participants who enroll in a clinical trial within six months of the intervention and changes in AIET subscale scores that reflect trust, perceived fairness, and understanding of clinical research. Additional questions assess general clinical trial literacy. Exploratory analyses will examine the same outcomes in non-Latinx participants. Statistical comparisons will be made using Fisher’s exact test and Wilcoxon rank-sum tests. Proportions will be reported with exact 95 percent confidence intervals. Significance & Vision The study is currently open to enrollment and is designed to inform scalable, culturally responsive strategies to improve equity in clinical trial participation for Latinx patients with cancer. Trial Schema

\"A noted Dutch journalist and economist proposes an outline for a new worldwide Utopia, with central tenets including a shortened work week, a guaranteed basic income for all, wealth redistribution, and open borders everywhere\"-- NoveList.

Abstract Background Farnesyltransferase inhibitors (FTIs) block post-translational modification of RAS and other farnesylated proteins. HRAS-driven tumors are highly sensitive to FTI treatment. Recent clinical trials (NCT03719690, NCT02383927) of the FTI tipifarnib in patients with HRAS-mutant (HRAS-m) head and neck squamous cell carcinoma harboring high variant allele frequency mutations (VAF ≥20%) showed objective response rates of up to 50% and favorable long-term outcomes. KO-2806 is a next-generation FTI that has increased potency and improved pharmacokinetic properties. Furthermore, in preclinical studies, KO-2806 has been shown to enhance tumor growth inhibition of tyrosine kinase inhibitors, including cabozantinib, in multiple clear cell (cc) renal cell carcinoma (RCC) cell line- and patient-derived xenograft models. These preclinical data support clinical investigation of KO-2806 in combination with cabozantinib in RCC. Methods FIT-001 is an ongoing first-in-human, multicenter, open-label Phase 1a/b clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics (PD), and preliminary antitumor activity of KO-2806 as monotherapy or in combination therapy in advanced solid tumors (NCT06026410; Figure). Up to 270 patients will be enrolled in Phase 1a and Phase 1b combined across approximately 50 sites. Phase 1a has separate monotherapy and combination dose-escalation arms. KO-2806 in combination with cabozantinib is being evaluated in RCC. Patients with advanced or metastatic ccRCC who progressed on ≥ 1 prior line of immunotherapy-based systemic therapy and patients with non-ccRCC who are treatment-naïve or who received any prior systemic therapy are eligible. On the basis of emerging data from Phase 1a, two PD cohorts (n ≤ 12) with mandatory pre- and on-treatment tumor biopsies may be enrolled. In Phase 1b dose expansion, patients will receive the recommended phase 2 dose (RP2D) of KO-2806 with cabozantinib or will be randomized by dose if two potential KO-2806 RP2Ds are identified for the combination. The study began accrual in October 2023, and recruitment is ongoing. Significance & Vision FIT-001 is assessing the safety, tolerability, pharmacokinetics, PD, and preliminary antitumor activity of KO-2806 in combination with cabozantinib in patients with ccRCC and non-ccRCC. Trial Schema

Abstract Background The role of combination immune therapy is not fully established in PRCC. The S1500 (PAPMET) clinical trial established single-agent cabozantinib as the standard of care for PRCC [PMID 33592176] with a median progression-free survival (PFS) of 9.0 months compared to 5.6 months with sunitinib. Additionally, trials have shown activity of PD-(L)1 antagonists as monotherapy [PMID 33529058] or in combination with targeted therapy [PMID 34491815]. In a single-arm study of cabozantinib/nivolumab the median PFS was 12.5 months [PMID 35298296]. In contrast, some data from retrospective studies suggest no benefit with combination therapy [PMID 36610815] over sequential single agent studies. Importantly no prior randomized studies of immune therapy in PRCC have compared sequential therapy versus upfront combination therapy. Toxicity is higher with combination therapy suggesting some equipoise and rationale for testing combinations in PRCC. We hypothesize that the combination will have higher clinical activity than single-agent cabozantinib while maintaining a reasonable quality of life. Methods This is a prospective randomized phase II clinical trial conducted through the NCTN and led by SWOG. The primary endpoint is a comparison of PFS between cabozantinib and cabozantinib/atezolizumab. Secondary endpoints include comparison of objective response rate, overall survival and safety. Patients are treated with cabozantinib 60mg/day versus cabozantinib 60mg/day + atezolizumab 1200 mg q3 weeks. Dose reductions of cabozantinib are allowed. Dose delays of either treatment are allowed. The sample size is planned for 200 patients to be enrolled and randomized 1:1 to each treatment arm. Treatment is allowed to continue even with discontinuation of the second agent in the combination arm. Significance & Vision Current clinical practice for patients with PRCC is defined by the approved treatment methods for clear cell RCC. It is unclear if combination strategies are as successful for PRCC as ccRCC. Additionally, the long-term follow up of prior TKI/IO studies in ccRCC do not demonstrate immunologic synergy suggesting that combination approaches might lead to increased toxicity without significant clinical benefit is many patients. Here we aim to establish the true clinical value of combination therapy for this disease. Additionally a rich biobank of liquid samples, soft-tissue tumor samples and stool samples will be collected in order to further basic scientific research with the aim of developing disease specific treatments for patients with PRCC. Trial Schema

Recent technological advances in hardware design of the robotic platforms enabled the implementation of various control modalities for improved interactions with humans and unstructured environments. An important application area for the integration of robots with such advanced interaction capabilities is human–robot collaboration. This aspect represents high socio-economic impacts and maintains the sense of purpose of the involved people, as the robots do not completely replace the humans from the work process. The research community’s recent surge of interest in this area has been devoted to the implementation of various methodologies to achieve intuitive and seamless human–robot-environment interactions by incorporating the collaborative partners’ superior capabilities, e.g. human’s cognitive and robot’s physical power generation capacity. In fact, the main purpose of this paper is to review the state-of-the-art on intermediate human–robot interfaces (bi-directional), robot control modalities, system stability, benchmarking and relevant use cases, and to extend views on the required future developments in the realm of human–robot collaboration.

Abstract Background Despite advances in the treatment of metastatic ccRCC, few patients are cured. Therapies exploiting novel targets are needed. Antigen screening identified ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase family member 3) as having consistent high expression in ccRCC and low expression in normal tissue. ENPP3 is a transmembrane ectoenzyme involved in hydrolysis of extracellular nucleotides. XmAb819 is a 2 + 1 bispecific antibody with high-avidity bivalent ENPP3 binding and mid-affinity monovalent CD3 binding. XmAb819 is engineered for preferential engagement and T cell-mediated cytolysis of high ENPP3-expressing cancer cells. Methods This is a multicenter, open-label, dose-escalation/expansion study enrolling up to 190 participants with advanced ccRCC. The primary objective is safety and tolerability; the secondary objective is preliminary anti-tumor activity. Part A, dose escalation, establishes a priming dose, step-up dose(s), a cohort-limit dose, and the dosing schedule for both intravenous (IV) and subcutaneous (SC) administration. Part B, dose expansion, evaluates the safety and efficacy of the recommended dose established in Part A. All subjects will have disease progression on standard-of-care therapies. XmAb819 will be administered weekly; cohort-limit doses will be administered in 21-day cycles until disease progression or unacceptable toxicity. Adverse events are graded using CTCAE v5.0; CRS using ASTCT Consensus Grading (Lee, 2019). Efficacy is assessed per investigator using RECIST v1.1. Enrollment and dose escalation continues in both the IV and SC cohorts. Significance & Vision XmAb819 is an investigational, novel bispecific T-cell engager engineered to bind and kill high ENPP3-expressing cells. The XmAb819-01 study is a trial designed to enroll patients with ccRCC, a solid tumor that overexpresses ENPP3. Initial evidence of anti-tumor activity in ccRCC has been observed, and tolerability supports continued dose escalation. Trial Schema The dosing period consists of priming, step-up, and target doses.