Bendigo

Researchers are evaluating a combination therapy using BNT324, a B7-H3 antibody-drug conjugate, with BNT327, a bispecific antibody targeting PD-L1 and VEGF, in people with advanced or relapsed small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). This two-part Phase Ib/II trial aims to find safe and effective dose levels and to assess the therapy's safety and clinical effects in different lung cancer groups, including treatment-nave and relapsed patients. The study uses a dose escalation design in Part 1 to establish two safe combination dose levels of BNT324 and BNT327. In Part 2, participants receive either the higher or lower recommended dose to determine the optimal dose for further study. Some groups are randomized to one of the two doses, while others receive the highest dose based on prior results. Both drugs are given by intravenous infusion during the treatment period. Participants undergo screening before starting treatment, followed by treatment and safety monitoring. Researchers track dose-limiting toxicities, adverse events, dose adjustments, and treatment discontinuations up to 90 days after treatment ends or until new anticancer therapy starts. They also evaluate objective response rates up to 87 months after the first dose. Ongoing survival follow-up is included to assess long-term outcomes and safety.

Researchers are evaluating LY3537021, a drug given by injection, to see how well it controls nausea and vomiting caused by chemotherapy in adults with cancer. This Phase 2 study compares LY3537021 to a placebo while participants also receive standard anti-nausea treatments. The study aims to understand the safety and effectiveness of LY3537021 during the period 24 to 120 hours after chemotherapy starts. Participants will receive chemotherapy drugs such as cisplatin or anthracycline with cyclophosphamide through an intravenous line. They will be randomly assigned to get either LY3537021 or a placebo, both given by subcutaneous injection, along with standard antiemetic therapies including medications taken by mouth, IV, or skin patches. The treatment period lasts through the chemotherapy cycle. During the study, participants will be monitored for their response to the anti-nausea treatment, particularly looking at how many achieve complete control of nausea and vomiting in the delayed phase after chemotherapy. Researchers will also track safety and any side effects. The entire participation may take about two months, covering all study parts until completion.

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 new treatments for acute hypoxemic respiratory failure (AHRF), a serious condition affecting millions worldwide and often requiring mechanical ventilation or extracorporeal life support. This adaptive platform trial includes multiple domains that assess different therapies across a range of patient severity and investigational phases, from early mechanistic studies to full clinical trials. The study uses advanced statistical methods to efficiently test interventions focusing on mechanical ventilation, extracorporeal support, drugs, and medical devices. Participants may receive various interventions depending on the domain, including ultra-protective ventilation using VV-ECMO, lung-protective ventilation, driving pressure-limited ventilation, lung- and diaphragm-protective ventilation with sedation, corticosteroid treatments, fludrocortisone, nebulized furosemide, or inspiratory muscle training. Some domains also study ventilation strategies during extracorporeal life support or collect observational data. Treatments are delivered according to randomized assignments, sometimes involving specialized devices or adjusted ventilator settings. During the study, participants undergo assessments including physiological and biological measurements, monitoring of ventilation targets, adherence to protocols, and survival outcomes up to 60 days. Recruitment feasibility and barriers are tracked over years at multiple sites. The trial collects data on ventilator-free days, mortality, advanced respiratory support-free days, and protocol adherence. Safety and effectiveness are regularly evaluated through Bayesian adaptive analyses, with total enrollment periods ranging from months to years depending on the domain.

Researchers are investigating treatment options for patients with advanced non-small cell lung cancer (NSCLC), a condition where current outcomes remain poor. This pilot study aims to evaluate the safety and feasibility of adding stereotactic ablative radiotherapy (SABR) to the lung primary tumor before starting standard systemic therapy. The study will focus on patients with stage IV NSCLC who have not yet received systemic therapy, testing whether radiotherapy can be safely delivered and assessing its impact on treatment outcomes. Participants will be randomly assigned to one of two groups: one receiving standard of care (SoC) systemic therapy alone, and the other receiving radiotherapy to the lung primary before the third cycle of systemic therapy. Radiotherapy doses vary depending on tumor location and size, with specific regimens for central, ultracentral, large, and peripheral tumors. Standard systemic therapy includes chemoimmunotherapy combinations such as Pembrolizumab with Carboplatin or Paclitaxel for squamous NSCLC, and Pembrolizumab with Carboplatin or Pemetrexed for non-squamous NSCLC, administered in cycles every three weeks. Throughout the study, participants will undergo regular assessments including radiation toxicity monitoring, adverse event tracking, and CT scans every six weeks to evaluate disease progression. Study visits occur at baseline, radiotherapy (for the radiotherapy group), cycle 3 of systemic therapy, and at 12 and 24 weeks post-treatment initiation. Biospecimens will also be collected for future research. The primary goal is to determine if the study design can proceed to a larger phase III trial without major modifications, with an overall recruitment and follow-up period of 18 months.

Researchers are evaluating the effectiveness of a personalized, stepped, multidisciplinary intervention delivered through a virtual multimodal rehabilitation hub for adults undergoing colorectal cancer surgery. This study aims to reduce postoperative complications within 30 days after surgery compared to usual care. Secondary goals include assessing quality of life, days spent at home after surgery, quality of recovery, cost-effectiveness, and implementation outcomes. The trial is a pragmatic randomized Type I hybrid effectiveness-implementation study involving 564 participants across Australia. Participants will be randomly assigned to either the virtual multimodal hub intervention or usual care. The intervention includes preoperative and postoperative components such as exercise (aerobic, endurance, respiratory, muscle strength, education), nutrition support (screening, weight monitoring, dietetic counseling), psychological support (CBT skills, emotional validation, psycho-education), nursing care (risk management, pain, wound and bowel/stoma care, education), and fortnightly peer support groups moderated by social workers. Allied health workers provide personalized virtual sessions before and after surgery, lasting up to 12 months or until treatment goals are met. Participants without internet access may receive tablets to facilitate virtual participation. During the study, participants will undergo baseline assessments and be monitored for postoperative complications within 30 days. Data collection includes patient-reported outcomes, quality of life questionnaires, and days at home at various intervals post-surgery. Safety is overseen by an independent Data and Safety Monitoring Board, with adherence to Good Clinical Practice guidelines. The total study duration is approximately 60 months, with ongoing assessments and support provided through the virtual hub and usual care pathways.

Researchers are evaluating the use of rademikibart as an additional treatment for adults and adolescents with asthma experiencing an acute exacerbation linked to type 2 inflammation. This Phase 2, randomized, double-blind, placebo-controlled trial aims to compare the effects of rademikibart plus standard therapy versus standard therapy alone in urgent healthcare settings. The study focuses on participants who have a history of asthma and require urgent treatment for an acute asthma exacerbation. Participants will receive either 600 mg of rademikibart administered subcutaneously via a prefilled syringe or a matching placebo injection alongside their standard asthma treatment. The trial is designed as a parallel-group study to assess the added impact of rademikibart during acute episodes. The treatment is given once during the urgent care visit for the exacerbation. Throughout the study, researchers will monitor participants for treatment failure within 28 days after randomization. Assessments include lung function tests such as FEV1, blood tests for eosinophil counts, and clinical evaluations of asthma control and exacerbation status. The trial also carefully tracks safety and efficacy outcomes during this 28-day period to understand how well rademikibart works as an add-on treatment.

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.

Researchers are investigating treatments for bloodstream infections caused by the bacterium Staphylococcus aureus, which can be deadly within three months of infection. This international, multi-center Phase 4 adaptive platform trial evaluates multiple treatment options simultaneously to identify those that reduce death rates within 90 days of infection. The trial adapts over time by assigning more patients to better-performing treatments, removing less effective ones, and adding new options, aiming to find the best combination of therapies for patients with this serious infection. Participants receive various antibiotic treatments such as Cefazolin, Penicillin, Clindamycin, Vancomycin or Daptomycin, as well as strategies like early switching to oral antibiotics. The trial also includes whole body FDG PET/CT imaging using standardized protocols to support diagnosis and treatment decisions. Patients are randomly assigned to different concurrent treatment options currently used in routine care, with ongoing adjustments based on accumulating results. During the study, participants undergo regular evaluations including blood culture monitoring to confirm infection clearance, clinical assessments, and imaging when applicable. Researchers track all-cause mortality up to 90 days after enrollment as the primary outcome. The trial infrastructure supports additional sub-studies, with patient safety and treatment effectiveness closely monitored throughout the trial period.

Researchers are evaluating the safety and initial antitumor effects of ORIC-944, an oral, selective small molecule inhibitor targeting the PRC2 complex, in patients with metastatic prostate cancer. The study is a first-in-human, open-label, multicenter phase 1/1b trial investigating ORIC-944 alone and combined with androgen receptor pathway inhibitors (ARPIs). The trial aims to establish safe dosing and explore preliminary effectiveness in this patient group. The study has three parts: Part I tests ORIC-944 alone through dose escalation; Part II combines ORIC-944 with ARPIs (such as abiraterone, apalutamide, darolutamide, or enzalutamide) to identify safe doses; Part III optimizes dosing for the combinations in two patient populations. Treatments are given orally and continuously, with different ARPI dosages depending on the drug used. The study evaluates two dose levels in combination with ARPIs to select the recommended phase 2 dose. Participants will undergo assessments including skin and tumor biopsies and regular monitoring of safety and drug levels. Researchers will measure pharmacokinetic outcomes like maximum plasma concentration and half-life, as well as clinical responses. The study includes follow-up to evaluate safety and preliminary antitumor activity over 12 months, with ongoing evaluation of drug exposure and effects.