Bankstown

Researchers are evaluating the safety, tolerability, and therapeutic effects of a combination treatment using BNT113 and pembrolizumab compared to pembrolizumab alone for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that is positive for human papillomavirus 16 (HPV16+) and expresses the PD-L1 protein with a combined positive score of 1 or higher. This Phase II/III trial includes patients whose cancer cannot be treated with local therapies and who have not received prior systemic anticancer therapy for their current disease condition. The trial consists of two parts. Part A is a non-randomized Safety Run-In Phase to confirm the safety and tolerability of BNT113 combined with pembrolizumab at the selected dose. Part B is a randomized phase that compares BNT113 plus pembrolizumab against pembrolizumab alone as first-line treatment. Patients in Part A continue their treatment without randomization. Treatments are given by intravenous injection or infusion, and patients may receive either combination therapy or monotherapy for up to 24 months. There is also an optional pre-screening phase to test tumor samples for HPV16 DNA and PD-L1 expression before entering the main trial. Participants undergo regular assessments including tumor measurements based on RECIST 1.1 criteria confirmed by independent review. Researchers monitor treatment-emergent adverse events for up to 27 months in Part A and evaluate overall survival and progression-free survival for up to 48 months in Part B. Tumor tissue samples are collected before treatment to confirm eligibility. The study involves ongoing safety monitoring and efficacy evaluations throughout the treatment and follow-up periods.

Researchers are evaluating the effectiveness and safety of pirtobrutinib in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The study focuses on two parts: Part 1 tests three different doses of pirtobrutinib in participants who have had 1 to 3 prior treatments, including a covalent Bruton tyrosine kinase (BTK) inhibitor. Part 2 evaluates pirtobrutinib alone in participants who have not received prior treatment but have a specific genetic deletion called 17p. This is a phase 2, open-label, randomized study. Pirtobrutinib is given orally to participants in both study parts. Participants in Part 1 receive one of three dose levels, while those in Part 2 receive pirtobrutinib monotherapy. Part 1 participation lasts about 3 years, and Part 2 participation can last up to 2 years. The study compares the effects of different doses and treatment histories to better understand pirtobrutinib’s impact on CLL/SLL. Throughout the study, researchers monitor participants' overall response to treatment from the start up to 3 years. They assess safety and side effects, and participants are required to be able to swallow oral medication and have a performance status that allows them to participate. The study includes regular evaluations to determine how well the treatment controls the disease and to track any adverse events over the course of the study periods.

Researchers are investigating the effects of low-dose intracoronary thrombolytic therapy in patients who experience ST-elevation myocardial infarction (STEMI), a type of heart attack caused by a blood clot blocking the heart's blood vessels. The study focuses on patients with impaired microcirculatory perfusion, identified by an elevated Index of Microcirculatory Resistance (IMR) after angioplasty. This damage to the heart's small vessels is linked to worse clinical outcomes, and the trial seeks to determine if dissolving clots inside the coronary artery can reduce this damage and improve patient outcomes. After patients receive angioplasty and a drug-eluting stent, their IMR is measured. Those with IMR above 32 are randomly assigned to receive either low-dose tenecteplase, a clot-dissolving drug, or a placebo of sterile water directly into the coronary artery. Patients with IMR 32 or below are monitored in a registry. The tenecteplase dose is one-third of the systemic weight-based dose, infused intracoronarily. Cardiac MRI scans are performed 3-7 days after the procedure and again at 6 months for randomized patients, with follow-up visits scheduled at 30 days, 6, 12, and 24 months. Throughout the study, participants undergo cardiac enzyme tests and clinical assessments. The primary outcomes measured include rates of cardiovascular death and rehospitalization for heart failure at 24 months, as well as the size of the heart attack and bleeding within the heart muscle at 6 months. The study carefully monitors safety and treatment effects through imaging and clinical follow-up to evaluate whether low-dose tenecteplase can improve long-term heart function after STEMI.

Researchers are evaluating the safety, effectiveness, and how the body processes zipalertinib in adults with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) that has specific mutations in the Epidermal Growth Factor Receptor (EGFR) gene, including exon 20 insertions and other uncommon mutations. This Phase 2b study also explores potential drug interactions of zipalertinib with certain enzyme and transporter substrates and aims to find the best dosing plan for the medication. Participants will be enrolled into one of four main groups based on their specific EGFR mutation status and treatment history. These groups include those previously treated with exon 20 insertion agents, those untreated and unsuitable for standard chemotherapy, those with active brain metastases or leptomeningeal disease, and those with other uncommon EGFR mutations without prior systemic therapy. Additionally, separate substudies will assess drug interactions using enzyme and transporter probe cocktails and will test different doses of zipalertinib in randomized groups until treatment discontinuation. Throughout the study, participants will undergo regular assessments including imaging scans, neurological exams, and laboratory tests to monitor disease progression and treatment safety. Researchers will track response rates over up to two years and evaluate brain metastasis stability when applicable. Safety monitoring, including cardiac function and adverse effects, will be ongoing. The study requires tissue samples to confirm mutation status and participants will be followed closely to evaluate the medication's impact and tolerability.

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with intermediate-high or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy). The planned duration of treatment in either arm of the study is 7 years. Eligible patients must have intermediate-high or high risk of recurrence as defined by specified clinical and biologic criteria. Concurrent use of abemaciclib is permitted in both arms. The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), Distant relapse-free survival (DRFS), Overall survival (OS), Safety and Clinical Outcome Assessments (COAs). Patients will be followed for 10 years from randomization of the last patient.

Researchers are evaluating the use of non-vitamin K oral anticoagulants (NOACs) compared to no anticoagulation in people who have experienced transient atrial fibrillation episodes triggered by stress and have additional risk factors for stroke. This multinational, investigator-initiated Phase 4 trial aims to prevent stroke and other serious cardiovascular events in this group by assessing the effects of NOACs on two main outcomes: the occurrence of non-hemorrhagic stroke or systemic embolism, and a combination of vascular death and other major cardiovascular problems, over a follow-up period lasting until the last participant reaches 24 months of observation. Participants in the study are randomly assigned to either receive one of several NOAC medications—edoxaban, apixaban, dabigatran, or rivaroxaban—with dosing adjusted as needed and chosen by their prescribing doctor, or to receive no oral anticoagulation. The treatment continues throughout the follow-up period. The trial is open-label, meaning both researchers and participants know which treatment is given. The study specifically focuses on patients who had transient atrial fibrillation related to stress, such as after certain surgeries or acute medical illness. During the study, participants undergo regular monitoring to track the incidence of stroke, embolism, vascular death, heart attacks, blood clots, and other cardiovascular events. Researchers collect information over up to two years to evaluate these outcomes. Safety and adherence to treatment are also monitored. This thorough follow-up helps determine the impact of NOAC treatment compared to no anticoagulation in this particular patient population.

Researchers are investigating treatments for patients with acute ischemic stroke caused by basilar artery occlusion within 24 hours of symptom onset. This trial is designed as a multi-arm, multi-stage, prospective, randomized, open-label study with blinded endpoint evaluation. It involves a seamless transition from phase 2b to phase 3 if early results meet success criteria. The main goal is to see if tenecteplase combined with mechanical thrombectomy is better than standard care, including alteplase or no thrombolytic treatment, in achieving excellent functional recovery or returning patients to their previous level of function by 90 days. Participants will be randomly assigned to receive either tenecteplase at 0.25 mg/kg as an intravenous bolus or standard care, which may include intravenous alteplase at 0.9 mg/kg administered as a bolus followed by an infusion. Treatments will be given before mechanical thrombectomy if needed, based on the treating clinician's judgment. The study uses an adaptive design with sample size adjustments based on interim analyses, with a minimum of 320 and a maximum of 688 patients planned. The trial will be conducted across multiple regions and centers, with randomization stratified by planned mechanical thrombectomy and alteplase use. During the 12-month participation period, patients will be assessed for recovery using the modified Rankin Scale at 90 days as the primary outcome. Researchers will monitor recanalization success without symptomatic brain bleeding as an intermediate outcome. Assessments include imaging to confirm the basilar artery occlusion, functional evaluations, and safety monitoring. The study aims to gather data on the best treatment approach to improve outcomes for this serious type of stroke.

Researchers are evaluating the safety and effectiveness of a new antibody drug called gotistobart (ONC-392/BNT316) compared to the chemotherapy drug docetaxel in patients with metastatic non-small cell lung cancer (NSCLC) whose disease has worsened after treatment with PD-1 or PD-L1 inhibitors. This Phase 3 clinical trial aims to see if gotistobart can help patients live longer than with standard chemotherapy. The study will enroll about 630 patients who have squamous cell NSCLC and have shown disease progression on prior immunotherapy. The trial has two stages. In Stage I, two different dosing regimens of gotistobart will be tested against docetaxel to confirm the best dose. Gotistobart is given through a 60-minute intravenous infusion every 21 days at either 3 mg/kg or 6 mg/kg (with two initial loading doses of 10 mg/kg). Docetaxel is given by IV infusion every 21 days at 75 mg/m2. Stage II will compare the chosen gotistobart dose to docetaxel in patients with squamous NSCLC. Treatment will continue for up to 17 cycles, approximately one year. Participants will undergo tumor measurements to confirm disease progression and meet health criteria such as organ function and performance status. Researchers will monitor overall survival over 36 months as the main outcome. Safety and side effects will be closely followed. The study requires patients to have recovered from prior treatment effects and have no active infections or serious heart or lung disease. Through this trial, researchers hope to determine whether gotistobart is a beneficial treatment option for this group of lung cancer patients.

Researchers are evaluating a range of treatments to improve outcomes for adults admitted to intensive care units (ICUs) with severe community-acquired pneumonia (CAP), including cases caused by influenza and COVID-19. This Phase 3 adaptive platform trial, REMAP-CAP, is designed to test multiple treatment strategies simultaneously and adapt over time, allowing new treatments to be added as questions are answered. The trial also serves as a platform to quickly evaluate treatments during respiratory pandemics, such as COVID-19, through a sub-study called REMAP-COVID in the United States. Participants receive various interventions including antibiotics like ceftriaxone, moxifloxacin, or piperacillin-tazobactam, as well as macrolide therapies given for different durations. Other treatments assessed include corticosteroids such as hydrocortisone and dexamethasone, antiviral agents like oseltamivir and remdesivir, immune modulators including tocilizumab and baricitinib, and supportive care strategies such as mechanical ventilation methods. Dosing and duration vary for each treatment, with some interventions now closed. Treatments are administered according to local guidelines and clinical decisions, with some requiring intravenous or enteral routes. Participants are closely monitored with assessments focusing on survival and organ support status in the ICU up to 90 days after enrollment. The main outcomes measured include all-cause mortality by day 90 and the number of days alive without needing organ support in the ICU by day 21. The study collects data continuously to adapt treatment assignments for new participants, aiming to identify the most effective therapies. Follow-up and safety monitoring continue throughout hospitalization and up to 90 days after admission.