Windsor

Researchers are evaluating nemtabrutinib compared with investigators choice of ibrutinib or acalabrutinib in adults with untreated chronic lymphocytic leukemia CLL or small lymphocytic lymphoma SLL. The study aims to assess whether nemtabrutinib is not worse than these comparators in terms of objective response rate and whether it can provide longer progression-free survival. This is a Phase 3 randomized clinical trial sponsored by Merck Sharp & Dohme LLC. Participants will receive either nemtabrutinib, ibrutinib, or acalabrutinib orally at specified doses until their disease progresses, unacceptable side effects occur, or other discontinuation criteria are met. The trial uses a parallel-group design where participants are randomly assigned to one of the treatment groups, and no masking is involved. Both treatment arms continue until progression or intolerance. During the study, participants will be monitored regularly up to about 33 months for response rate and up to about 104 months for progression-free survival and overall survival. Assessments include clinical evaluations, safety monitoring for adverse events, and duration of response measurements. The study tracks treatment tolerability, discontinuations due to adverse events, and overall outcomes to better understand the therapies effects in this patient population.

Researchers are evaluating the efficacy and safety of opevesostat combined with daily corticosteroids compared to alternative treatments abiraterone acetate or enzalutamide in participants with metastatic castration-resistant prostate cancer mCRPC who have previously been treated with one next-generation hormonal agent NHA. The study aims to determine if opevesostat offers better control of disease progression assessed by radiographic progression-free survival, including participants with and without androgen receptor ligand binding domain mutations. Overall survival has also been included as a secondary outcome measure. Participants are randomly assigned to one of two groups. One group receives opevesostat 5 mg orally twice daily, plus dexamethasone 1.5 mg and fludrocortisone acetate 0.1 mg orally once daily, continuing until disease progression. Hydrocortisone is available as a rescue medication if needed. The other group receives either abiraterone 1000 mg once daily with prednisone 5 mg twice daily or enzalutamide 160 mg once daily, also until disease progression. This open-label, phase 3 study compares these two treatment approaches in a parallel design. During the study, participants undergo regular assessments including imaging scans to measure disease progression, safety monitoring, and evaluations of overall survival and quality of life. Researchers track radiographic progression-free survival for up to 52 months and secondary outcomes such as overall survival, time to new treatments, pain progression, and prostate-specific antigen PSA responses for up to approximately 82 months. Participants are closely monitored for adverse events and treatment tolerability throughout the study duration, which spans several years.

Researchers are evaluating whether skipping additional axillary treatment for patients with early-stage breast cancer who had cancer in their lymph nodes before chemotherapy but show no remaining cancer in those nodes after treatment is as effective as the standard approach. This study focuses on disease-free survival and reducing the risk of lymphoedema five years after treatment. It is a randomized, open, multicenter trial including patients with specific breast cancer stages and confirmed nodal metastases. Participants will all receive standard therapies including HER2-targeted treatment, endocrine therapy, and radiotherapy to the breast or chest wall if needed. They will be randomly assigned to one of two groups one group will not get further axillary treatment such as lymph node removal or radiotherapy, while the other group will receive these axillary treatments according to local guidelines. Follow-up visits will occur annually for at least five years. During the study, participants will undergo assessments to monitor disease-free survival and self-reported lymphoedema using specific questionnaires. Additional evaluations include arm function, quality of life, recurrence rates, survival, and cost-effectiveness analyses. The total study duration is planned for 120 months, including setup, recruitment, follow-up, analysis, and reporting.

Researchers are evaluating the safety and efficacy of nemtabrutinib in adults with various blood cancers, including chronic lymphocytic leukemia CLL, small lymphocytic lymphoma SLL, Richters transformation, marginal zone lymphoma MZL, mantle cell lymphoma MCL, follicular lymphoma FL, and Waldenstrms macroglobulinemia WM. The study is a phase 2 clinical trial sponsored by Merck Sharp & Dohme LLC, designed to explore how well nemtabrutinib works and its safety profile in these hematologic malignancies. The study has two parts Part 1 focuses on dose escalation and confirmation to identify the recommended phase 2 dose, while Part 2 involves cohort expansion across eight disease-specific groups. Participants take nemtabrutinib tablets orally once daily until their disease progresses or they stop treatment. This approach allows researchers to assess responses across different types of blood cancer and treatment histories. Participants will be involved in regular assessments including monitoring for adverse events, evaluating response rates using established criteria for each disease type, and biomarker analysis from biopsies or bone marrow samples. Safety and response will be tracked over several months, up to about five to six years. The study also monitors drug levels in the body and collects detailed data on how participants tolerate the treatment during this period.

Researchers are studying whether adding navtemadlin to ruxolitinib treatment can provide more benefit than ruxolitinib alone for adults with Myelofibrosis who have not responded well to ruxolitinib by itself. This Phase 3 trial includes patients who are new to JAK inhibitor treatment and have a confirmed diagnosis of primary or post-polycythemia vera or post-essential thrombocythemia Myelofibrosis. The study aims to assess improvements in spleen size and symptom reduction over 24 weeks, as well as long-term outcomes like disease progression and overall survival. Participants first receive ruxolitinib alone during a run-in period to identify those with suboptimal response. Those qualifying are randomly assigned in a 21 ratio to receive either navtemadlin or a placebo as an add-on to their ongoing ruxolitinib. Navtemadlin or placebo is taken orally once daily for 7 days followed by 21 days off in 28-day cycles, while ruxolitinib is taken twice daily continuously. The study is double-blinded so neither participants nor researchers know which add-on treatment is given. During the trial, participants will undergo evaluations including spleen volume measurements and symptom assessments at 24 weeks. They will be monitored for disease progression and survival for up to 8 years. The study includes regular check-ups to track side effects, treatment adherence, and overall health status. These detailed assessments help researchers understand the potential benefits and safety of adding navtemadlin for patients with Myelofibrosis.

Researchers are studying metastatic castration-resistant prostate cancer in men who have progressed after treatment with androgen receptor pathway inhibitors. The study aims to compare the length of time patients live without their cancer worsening on imaging when treated with 177Lu-TLX591 plus standard care versus standard care alone. This is a Phase 3 trial with a focus on both efficacy and safety of the new treatment in this patient group. Participants are divided into three parts a safety and dosimetry lead-in with 30 patients, a randomized treatment expansion with approximately 490 patients, and a long-term follow-up period lasting at least 5 years. In the randomized phase, patients receive either 177Lu-TLX591 plus standard of care, which may include enzalutamide, abiraterone, or docetaxel, or standard of care alone. The 177Lu-TLX591 is given as two doses about 14 days apart. Standard care treatments involve oral medications or chemotherapy as specified. During the study, participants will be regularly monitored through scans and other assessments to evaluate cancer progression and safety. Imaging includes PETCT or PETMRI scans to confirm PSMA positivity and detect disease spread. Researchers will track radiographic progression-free survival as the main outcome, along with overall survival and response rates. The long-term follow-up helps assess lasting effects and safety over several years. Participants are expected to adhere to study protocols and radiation safety precautions throughout their involvement.