Ciuded De Mexico, Mexico

Phase 1/2 Study of IMC-R117C in Selected Advanced Cancers

A First-in-Human Open-label, Phase I/Ib Dose Escalation and Expansion Cohort Study of EOS006215 as Monotherapy and in Combination With Pembrolizumab or Other Anticancer Treatments in Participants With Advanced Solid Tumors

The study will be conducted in 2 parts: - Part 1 - Dose Escalation Phase I dose escalation cohorts for EOS006215 as monotherapy and in combination with anticancer treatments in participants with specific tumor types. - Part 2 - Dose Expansion Phase Ib dose expansion cohort(s) may be included to further evaluate the safety, tolerability, efficacy, PK and PD of EOS006215 as monotherapy or in combination with anticancer treatments in participants with specific tumor types.

The Dragon PLC Trial (DRAGON-PLC)

Primary liver cancer (PLC) is the third most common cause of cancer death worldwide. Surgical resection is the mainstay for a curative approach as contemporary chemotherapy and immune-based therapies only lead to a median survival of 10-14 months. A complete surgical resection increases the median survival to 42 months (range 32-52 months). However, PLC is mainly diagnosed at an advanced stage and >70% of PLC patients are ineligible for an immediate surgical approach. There are different reasons that make a patient ineligible for surgery, one important reason is the risk of liver failure after the surgery due to a small remnant liver. This study aims to improve the oncological, radiological and surgical strategy to allow more patients to undergo liver resection safely, to improve quality of life and to extend overall survival at acceptable costs. Adequate function of the future liver remnant (FLR) is a prerequisite for surgical resectability. This is necessary in order to avoid liver failure after surgery, a major cause of morbidity (38%) and mortality (27%). To mitigate this risk, regenerative strategies based on preoperative calculation of the FLR volume and function are essential. Patients with technically resectable disease but predicted insufficient FLR volume or function are referred to as primarily unresectable or potentially resectable (PU/PR). These patients can undergo strategies that capitalize on the regenerative capacity of the liver which aim to preoperatively increase the FLR volume and function in order to allow surgery. Many of the patients that are primarily unresectable due to an insufficient FLR can become ultimately and safely resectable after the induction of adequate FLR-hypertrophy by the current standard, portal vein embolisation (PVE). However, 25% of patients do not show sufficient FLR growth after PVE and are unable to safely undergo resection. A new approach has been developed to improve this. Combined portal and hepatic vein embolisation (PVE/HVE) has great promise in terms of increasing FLR growth, resection rate (RR), safety and potentially, overall survival. Establishing PVE/HVE as the new standard could result in increased survival and a better quality of life (QoL) for patients.

A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)

Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation-2 (TELSTAR-2)

Rationale: Around 7500 comatose patients after cardiac arrest and resuscitation are admitted to intensive care units (ICUs) in the Netherlands and Belgium, yearly. Approximately half eventually dies from severe brain injury. EEG is used as a predictor of outcome, helping decide whether life sustaining therapies should be pursued or withdrawn. EEG shows epileptiform patterns meeting criteria for electrographic status epilepticus (ESE) in up to 10% of patients, with 80-100% case fatality. With the TELSTAR-1 trial, we showed that anti-seizure treatment of unselected patients with epileptiform patterns is not associated with a better outcome. However, it remains unclear whether treatment of (possible) ESE will improve outcome, or if ESE simply represents irreversible severe brain damage, in which case such treatment will be futile. This translates into ongoing practice variation. To provide comatose cardiac arrest survivors with the best medical treatment options, while at the same time preventing unnecessary costly ICU treatment, unequivocal evidence of efficacy or futility of ESE treatment is needed. Objectives: It is the primary objective to study whether ESE treatment improves outcome of comatose patients after cardiac arrest. It is the secondary objective to study the impact on healthcare costs of ESE treatment. Main trial endpoints: The primary outcome measure will be functional recovery expressed as the score on the extended Glasgow Outcome Scale (eGOS) at six months after cardiac arrest. The primary effect parameter will be the common odds ratio for any shift towards a better outcome in the intervention group, analyzed by multivariable ordinal logistic regression. Secondary trial endpoints: Secondary outcome measures include data on quality of life, cognitive functioning, and the use of resources. Cost-effectiveness will be assessed, separately for Belgium and for the Netherlands, adhering to 'KCE' and 'Zorginstituut' guidelines for pharmaco-economic evaluations, respectively. Trial design: This will be a comparative effectiveness study, comparing two standard treatment regimens. We will conduct a prospective multicentre trial with randomized treatment allocation, open label treatment, and blinded endpoint assessment on twenty intensive care units in the Netherlands and Belgium. Trial population: The study population consists of adult comatose patients after out of hospital cardiac arrest and successful cardiopulmonary resuscitation, admitted on the intensive care unit of any of the participating centres, with ESE on continuous EEG. Continuous EEG is part of standard care in all participating hospitals. For the definition of ESE, we adhere to international consensus criteria. Interventions: Treatment in the intervention group will consist of standard care completed with anti-seizure treatment according to protocols for clinically overt status epilepticus with the goal of definitive seizure suppression. This consists of a stepwise approach, step 1 being a single dose of a parenteral benzodiazepine (lorazepam, midazolam, or diazepam) and a first parenteral anti-seizure medication (levetiracetam, valproate, or lacosamide), step 2, a second parenteral anti-seizure medication plus a first continuous parenteral sedative agent (midazolam or propofol), and step 3, a second continuous parenteral sedative agent (midazolam, propofol, or ketamine). Each next step will be taken as soon as possible (within 30 minutes) if the previous step was insufficiently effective to suppress ESE. The control group will receive standard care without anti-seizure treatment.

CRS Questionnaire Validation Project

The objectives of this study are as follows: - Validation of two new questionnaires with the aim of measuring the current perceived condition of a patient with chronic rhinosinusitis in terms of control and severity. - Validation of these questionnaires in routine medical settings. - Evaluation of the results of these questionnaires in comparison with other tools currently available.

Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types

A Study to Evaluate the Safety, Tolerability, and Effects on Blood and Urine Markers of Single Ascending Dose of GSK4771261 in Healthy Participants and Participants With Autosomal Dominant Polycystic Kidney Disease

Study of Eftilagimod Alfa (Efti) in Combination With Pembrolizumab and Chemotherapy Versus Placebo in Combination With Pembrolizumab and Chemotherapy in Participants With Metastatic Non-Small Cell Lung Cancer (NSCLC) (TACTI-004)

TACTI-004 is a double-blinded, randomized phase 3 trial in patients with advanced/metastatic non-small cell lung cancer (NSCLC) receiving eftilagimod alfa (major histocompatibility complex (MHC) class II agonist) in combination with pembrolizumab (programmed cell death protein 1 (PD-1) antagonist) and chemotherapy. The proposed clinical trial aims to compare the efficacy and to demonstrate the superiority of efti combined with standard of care (SoC, pembrolizumab and histology-based chemotherapy) compared to placebo combined with SoC in programmed death-ligand 1 (PD-L1) unselected population as assessed by: - Overall survival [OS] - Progression-free survival [PFS] per RECIST 1.1 The trial is planned to be conducted in countries in Asia, Australia, Europe and North and South America in approximately 175 experienced clinical sites.

Clinical Validation of BoneMRI in the Spine

Rationale: BoneMRI is a quantitative 3D MRI technique that has been developed recently by MRIGuidance BV©, which is based on a multiple gradient-echo sequence and a machine learning processing pipeline. The BoneMRI technology is capable of generating CT-like, quantitative radiodensity bone MRI images to visualize cortical and trabecular bone, allowing to assess bone structure and morphology, in addition to regular clinical MRI images. The use of BoneMRI has been investigated and clinically validated in multiple musculoskeletal studies involving the cervical spine, hip and sacro-iliac joint. In order to clinically use BoneMRI in the entire spine, the BoneMRI technology needs to be validated in that area as well, focussing on geometrical and voxelwise accuracy of the radiodensity contrast to assure accurate visualization of the osseous structures. As robustness against expected data variability between hospitals is crucial for successful machine learning algorithms, multiple MR field strengths and scanner types from different manufacturers will be included in this study. If successful, BoneMRI will facilitate a better, easier and cheaper workflow by enabling diagnosis, treatment planning and surgical navigation using a single radiological examination, without the potential hazards of ionizing radiation. Primary objective: The primary objective of this study is to investigate the performance of BoneMRI in terms of geometrical accurate visualization of the spinal osseous structures by radiodensity reconstruction when exposed to clinically relevant data variability. Study design: This study is a prospective multi-center clinical validation study, following a comparative design. Study population: Subjects referred to the radiology department for an MRI and CT scan of the spine having symptoms related to a spine disorder with suspected underlying involvement of osseous structures, will be asked to participate in this study. Duration of the study: Expectation is that it will take approximately 36-48 months to include 50 patients per center. Main study parameters/endpoints: Geometric accuracy in terms of visualization of the 3D osseous morphology of the spinal column. Nature and extent of the burden and risk associated with participation, benefit and group relatedness: The patient does not benefit from participating in this study and will receive routine care, which includes undergoing an MRI and CT scan. For research purposes an additional MRI sequence will be obtained for each patient. The CT scan is part of routine clinical care, so patients do not receive additional ionizing radiation compared to standard care. The subjects will in no way be exposed to BoneMRI as BoneMRI will not be installed at the investigation site and will not be part of the clinical workflow, nor the BoneMRI reconstructions will be part of the patient's file or decision making process of the healthcare professional. Therefore, there are no additional risks for the patients when participating in this study. This study may contribute to lower radiation doses in future patients when concluded that BoneMRI accurately visualizes the 3D morphology of the spinal osseous structures. This would render an additional conventional CT scan redundant.