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Researchers are evaluating the effectiveness of pembrolizumab combined with sacituzumab govitecan-hziy compared to standard chemotherapy treatments in patients with advanced urothelial cancer that has spread locally or to other parts of the body. This phase III trial focuses on patients whose cancer has not responded to prior anti-PDL1 therapy. The study aims to compare overall survival, progression-free survival, response rates, duration of response, treatment side effects, and quality of life between the new combination therapy and usual chemotherapy care. Participants are randomly assigned to one of two treatment groups. One group receives standard chemotherapy options such as carboplatin or cisplatin with gemcitabine, or alternatively docetaxel or paclitaxel, given intravenously in 21-day cycles for up to six cycles or until disease progression or unacceptable side effects. The other group receives pembrolizumab intravenously on day 1 and sacituzumab govitecan-hziy intravenously on days 1 and 8 every 21 days for up to 35 cycles or two years, unless disease progresses or side effects become unacceptable. Both groups undergo blood tests and imaging scans like CT or MRI throughout the study. During the trial, participants will have regular assessments including blood sample collection and imaging to monitor their cancer status and treatment effects. Researchers will also evaluate patient-reported quality of life and fatigue at multiple time points up to 12 months. After completing treatment, participants are followed up 30 days later and then annually for five years to track survival and health outcomes. This comprehensive approach helps researchers understand both the clinical outcomes and the impact on patients well-being over time.

Researchers are evaluating the efficacy and safety of the combination of divarasib and pembrolizumab compared with pembrolizumab combined with pemetrexed and either carboplatin or cisplatin. This study focuses on adults with previously untreated, advanced or metastatic non-squamous non-small cell lung cancer NSCLC that has a KRAS G12C mutation. The goal is to assess these treatments as first-line options in this specific lung cancer population. Participants will be randomly assigned to one of two groups. One group will take divarasib orally once daily and receive pembrolizumab through an intravenous infusion every three weeks. The other group will receive pembrolizumab, pemetrexed, and either carboplatin or cisplatin via intravenous infusions every three weeks. Treatment continues with these schedules, following the study protocol for up to approximately five years of follow-up. During the study, participants will have regular assessments to monitor their health and response to treatment. These include imaging and clinical evaluations to measure progression-free survival and overall survival for up to five years. Researchers will also track quality of life, symptom changes, treatment side effects, and adverse events using questionnaires and patient-reported outcomes. Safety monitoring and detailed evaluations will help understand the effects of the treatments over the study duration.

Researchers are evaluating the effectiveness of amivantamab combined with either lazertinib or platinum-based chemotherapy in treating participants who have epidermal growth factor receptor mutated EGFRm non-small cell lung cancer NSCLC. This study focuses on advanced or metastatic NSCLC cases where standard curative treatments are not suitable. It aims to assess the antitumor activity of these treatment combinations in this patient population. Participants receive either amivantamab with oral lazertinib in 28-day cycles or amivantamab with intravenous chemotherapy consisting of carboplatin and pemetrexed in 21-day cycles. Treatment continues until disease progression, participant withdrawal, death, or investigator decision to stop treatment. The study is designed with two separate groups receiving these distinct treatment combinations. Throughout the study, participants will undergo assessments to monitor treatment effects and safety. Researchers will measure progression-free survival as the primary outcome up to 4 years and 6 months, along with secondary outcomes including dose adjustments, adverse events, overall survival, response rates, and duration of response. Participants are followed regularly during treatment to track these outcomes and manage any side effects until the studys completion.

Researchers are evaluating the combination of sonrotoclax plus zanubrutinib compared with zanubrutinib plus placebo in adults with relapsed or refractory mantle cell lymphoma MCL. This Phase 3 randomized, double-blind study aims to compare how well these treatments work and assess their safety in this patient population. The study is sponsored by BeOne Medicines and focuses on patients who have previously received 1 to 5 prior systemic therapies including anti-CD20 monoclonal antibody or chemoimmunotherapy. Participants will receive either sonrotoclax plus zanubrutinib or placebo plus zanubrutinib, both administered orally. The study has two groups one receiving the combination of sonrotoclax and zanubrutinib, and the other receiving zanubrutinib with placebo. Treatment continues as per protocol, and the study includes detailed assessments of response and safety over time. During the study, participants will be monitored for progression-free survival as the primary outcome, assessed by an independent review committee over approximately 41 months. Secondary outcomes include overall survival, response rates, duration of response, health-related quality of life, and adverse events up to around 58 months. Regular evaluations will be conducted to assess disease status, quality of life, and safety throughout the trial, which is planned to complete by 2032.

Researchers are evaluating ziltivekimab, a new medicine not yet approved anywhere, to see if it can help people who were hospitalized due to a heart attack. The study aims to find out if ziltivekimab can reduce the development of heart disease and prevent future heart attacks or strokes. This is a Phase 3 clinical trial comparing ziltivekimab to a placebo in patients with acute myocardial infarction. Participants will receive an initial loading dose of ziltivekimab or matching placebo by injection under the skin as soon as possible after an invasive heart procedure, within 36 hours for STEMI or 48 hours for NSTEMI patients. After the loading dose, they will get monthly injections of the same study medicine for up to two years, in addition to their standard care. During the study, participants will be monitored for major cardiovascular events such as heart attack, stroke, and cardiovascular death. Researchers will also track other heart-related outcomes and safety measures over a period of up to 25 months. The study involves regular visits for injections, assessments, and laboratory tests to evaluate the medicines effects and patient health throughout the trial.

Researchers are evaluating the efficacy and safety of BGB-43395 combined with letrozole compared to an investigators choice of cyclin-dependent kinase 46 inhibitors CDK46i combined with letrozole in patients who have advanced or metastatic hormone receptor positive HR and human epidermal growth factor receptor 2 negative HER2- breast cancer. This study focuses on patients who have not received prior systemic treatment for their advanced or metastatic disease. The trial is a phase 3, open-label, randomized study sponsored by BeOne Medicines. Participants will be randomly assigned to one of two treatment groups. One group will receive oral BGB-43395 plus letrozole, while the other group will receive one of the CDK46 inhibitors abemaciclib, palbociclib, or ribociclib combined with letrozole, both administered orally. Treatments will be given according to the investigators choice for the comparator group. The studys primary treatment period is expected to last up to approximately 4 years for progression-free survival assessment, with follow-up extending up to approximately 11 years for overall survival and safety monitoring. During the study, participants will attend regular visits for treatment administration and monitoring. Researchers will assess progression-free survival as the primary outcome, with additional measures including overall survival, response rates, duration of response, clinical benefit, and safety assessments. Quality of life will be evaluated using the European Organisation for Research and Treatment of Cancer EORTC questionnaires. Safety will be monitored from the first dose until 30 days after the last dose, with long-term follow-up lasting up to approximately 11 years. Total participation duration may extend over this period depending on individual outcomes and monitoring requirements.

Researchers are investigating the long-term safety and effectiveness of Cardiac Contractility Modulation CCM therapy in people with heart failure. This global study combines both past and future patient data to observe how CCM therapy, delivered through Impulse Dynamics devices, performs in real-world settings over extended periods. The goal is to better understand CCM therapys impact on heart failure outcomes and any related device or procedure complications. The study includes patients who have already received or will receive CCM therapy using Impulse Dynamics systems, including future technologies like CCM-D. It is a single-arm observational study without experimental treatment groups, following patients for at least five years after their therapy. Patients are grouped into prospective, retrospective, and hybrid cohorts based on when they receive or received the CCM therapy. Participants will be monitored through regular follow-ups to assess hospitalization rates and length of stay due to heart failure, safety regarding device-related complications, and various clinical outcomes such as mortality, functional capacity, and heart remodeling. Additional evaluations include quality of life measurements using the Kansas City Cardiomyopathy Questionnaire and assessments of therapy compliance. The study duration allows detailed observation of CCM therapy effects and patient health over several years, up to at least five years.

Researchers are evaluating treatments for older adults aged 70 and above with advanced stage IIIB-IV non-small cell lung cancer that expresses PD-L1 in 1-49% of tumor cells. This phase III trial compares the effects of adding chemotherapy to immunotherapy with pembrolizumab against pembrolizumab alone. The study aims to assess improvements in overall survival, progression-free survival, response rates, toxicity, quality of life, and explore geriatric assessment factors and gut microbiome correlations. Participants are randomly assigned to one of two groups. Arm A receives pembrolizumab intravenously every 21 days for four cycles, followed by maintenance pembrolizumab every 21 or 42 days for up to two years. Arm B receives the same pembrolizumab schedule plus one of several chemotherapy regimens, including combinations of pemetrexed, carboplatin, nab-paclitaxel, or paclitaxel administered intravenously on different schedules for four cycles, followed by pembrolizumab maintenance. Imaging with MRI, CT, and PET scans is performed at baseline and throughout the trial. During the study, participants undergo regular assessments including imaging scans to monitor disease status, blood tests, and quality of life questionnaires. After treatment completion, follow-up visits occur every three months for up to two years and then every six months up to five years. Researchers measure overall survival as the primary outcome and also track progression-free survival, response rates, adverse events, and patient-reported quality of life. Safety and tolerability are closely monitored along with exploratory analyses of chemotherapy dose intensity and microbiome factors.

Researchers are collecting blood and tissue samples from people with and without cancer to help evaluate new tests that could detect cancer early. This study aims to create a set of blinded blood samples from both cancer and non-cancer patients to validate these tests, focusing on multiple cancer types and stages. The goal is to improve early cancer detection through laboratory research. Participants complete a questionnaire at the start and provide blood samples at registration and again 12 months later. Those diagnosed with cancer may also have tissue samples collected at these times. The study includes patients with various cancer types and stages, as well as individuals without cancer, with some allowing enrollment before full cancer confirmation under specific conditions. During the study, researchers review the collected samples and questionnaire data to assess test performance by tumor type and clinical stage at diagnosis. Participants are followed for one year after completing the study. Key measurements include the provision of a blinded reference set of cancer versus non-cancer blood samples to support future clinical trials focused on blood-based multi-cancer early detection.

Researchers are evaluating how to best recommend chemotherapy for patients with Stage IIB, IIC, or Stage III colon cancer based on the presence or absence of circulating tumor DNA ctDNA after surgery. This Phase IIIII trial explores whether ctDNA status can help guide decisions about the need for adjuvant chemotherapy and identify the optimal chemotherapy regimen for those at high risk of recurrence. Circulating tumor DNA is a promising biomarker that may detect microscopic residual cancer cells that traditional methods might miss. Participants are assigned to groups based on their ctDNA results after surgery. Those without detectable ctDNA ctDNA- may undergo serial monitoring without treatment or receive different chemotherapy regimens such as mFOLFOX6 or CAPOX for 3 to 6 months. Patients with detectable ctDNA ctDNA who have a higher risk of recurrence are randomized to receive either standard chemotherapy regimens like mFOLFOX6 or CAPOX for 6 months or a more intensive regimen called mFOLFIRINOX for 6 months. Central ctDNA testing is performed using the Signatera test to guide these assignments. During the study, participants have blood samples collected for ctDNA testing and undergo imaging scans to check for cancer recurrence. Researchers assess disease-free survival, overall survival, and chemotherapy compliance over several years. The study includes monitoring for safety and treatment effects, with follow-up planned for up to 5 years after randomization. Participants health status, laboratory tests, and tumor markers are regularly evaluated throughout the treatment and follow-up periods.