Cheltenham

Researchers are evaluating the safety and effectiveness of combining durvalumab and domvanalimab compared to durvalumab plus placebo in adults with locally advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) whose disease has not worsened after definitive platinum-based concurrent chemoradiation therapy. This Phase III, randomized, double-blind, placebo-controlled, international study involves multiple centers. Participants receive intravenous infusions of durvalumab and domvanalimab or durvalumab and placebo. The treatments are given after patients have completed concurrent platinum-based chemotherapy and radiation therapy with a total radiation dose of approximately 60 Gy. The study monitors patients over time to assess treatment effects and safety. During the study, participants undergo evaluations including tumor tissue analysis for PD-L1 status, performance status assessments, and monitoring of organ and marrow function. The main outcome measured is progression-free survival up to 8 years after randomization. Researchers also monitor for any adverse effects and disease progression throughout the study period.

The purpose of this study is to assess the anti-tumor activity and safety of amivantamab which will be administered as a co-formulation with recombinant human hyaluronidase PH20 (rHuPH20) (subcutaneous co-formulation \[SC-CF\]) in combination treatment (all cohorts except Cohort 4) and to characterize the safety of amivantamab SC-CF (Cohort 4).

Researchers are evaluating how well elacestrant works compared to standard endocrine therapy in adults with node-positive, Estrogen Receptor-positive (ER+), Human Epidermal Growth Factor-2 negative (HER2-) early breast cancer who are at high risk of the cancer returning. This is a Phase 3 global, multicenter, randomized, open-label study focusing on participants who have had early invasive breast cancer removed and meet specific receptor and risk criteria. The study aims to understand which treatment better prevents invasive breast cancer over up to five years. Participants will receive either elacestrant or one of several standard endocrine therapies, including anastrozole, letrozole, exemestane, or tamoxifen, all given as oral tablets. Treatments will be administered according to the study plan, with careful monitoring throughout the trial. The study includes adults who have already received between 24 and 60 months of prior endocrine therapy, with or without certain inhibitors, and who have completed or stopped these treatments as required. During the study, participants will be monitored for invasive breast cancer-free survival for up to five years. Researchers will perform regular assessments to track treatment effects, side effects, and cancer recurrence. The study also includes safety monitoring and may involve additional tests or evaluations as needed to ensure participant well-being throughout the trial.

Researchers are evaluating the safety and effectiveness of advanced external beam radiotherapy called stereotactic body radiotherapy (SBRT) in men with high risk localized prostate cancer. This cancer is limited to the prostate but has a high chance of growing quickly or spreading. The study compares SBRT given to the prostate alone versus SBRT given to both the prostate and surrounding lymph nodes. It is a Phase III trial involving 1128 participants to see which treatment option is better and safer over at least three and a half years of follow-up. Participants receive radiotherapy in 5 visits over two weeks. Half of the men will have SBRT targeted only to the prostate, while the other half will have it directed to both the prostate and pelvic lymph nodes. The treatments are delivered at NHS radiotherapy centers experienced with SBRT and pelvic node radiotherapy. Quality assurance ensures the treatments are administered properly. During the study, men will undergo scans including multi-parametric MRI and various types of PET-CT or MRI to stage their cancer before treatment. Researchers will monitor side effects and cancer outcomes to assess safety and effectiveness. The main outcome measured is the time until biochemical or clinical failure, with a minimum follow-up of 3.5 years after randomization. Participants will be closely followed for side effects and cancer control throughout the study period.

Researchers are evaluating whether avoiding further axillary treatment after neoadjuvant chemotherapy (NACT) is as effective as standard axillary treatment for patients with early stage breast cancer who initially had cancer in the lymph nodes confirmed by needle biopsy but show no residual cancer in the lymph nodes after NACT. The study aims to determine if skipping axillary lymph node dissection (ALND) or axillary radiotherapy (ART) affects disease free survival (DFS) and whether it reduces the risk of lymphoedema five years after treatment. This phase 3, open-label, randomized trial includes patients with T1-3N1M0 breast cancer and confirmed nodal metastases who have undergone sentinel node biopsy removing at least three lymph nodes post-NACT.

Researchers are evaluating the safety and effectiveness of mirvetuximab soravtansine combined with bevacizumab as maintenance therapy in adult women with platinum-sensitive ovarian, primary peritoneal, or fallopian tube cancers that have high folate receptor-alpha (FRα) expression. This Phase 3, multicenter, open-label study focuses on patients who have not progressed after second-line platinum-based chemotherapy plus bevacizumab. Participants must have tumors confirmed as FRα-positive using the Ventana FOLR1 assay. Participants will be assigned to receive either mirvetuximab soravtansine at 6.0 mg/kg adjusted ideal body weight plus bevacizumab at 15 mg/kg every 3 weeks, or bevacizumab alone at 15 mg/kg every 3 weeks. Mirvetuximab soravtansine is an investigational antibody drug conjugate designed to selectively kill cancer cells expressing FRα. The treatment is given as maintenance therapy following prior platinum-based chemotherapy and bevacizumab. During the study, participants will undergo regular assessments to monitor progression-free survival for up to 4 years. Researchers will evaluate disease status and safety through clinical evaluations. Participants will also need to adhere to contraceptive requirements during treatment and for several months after. The study aims to understand how well the treatment combination controls cancer without progression and to assess its safety profile over time.

Researchers are evaluating the effectiveness and safety of Datopotamab Deruxtecan (Dato-DXd) combined with Rilvegostomig or Rilvegostomig alone compared to Pembrolizumab alone as first-line treatments for adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). Participants must have high PD-L1 expression (tumor cells 50% or greater) and no actionable genetic changes. This Phase III, randomized, open-label global study focuses on this specific group of lung cancer patients without known targetable mutations. The trial includes three treatment groups: one receiving Dato-DXd plus Rilvegostomig intravenously, one receiving Rilvegostomig alone intravenously, and one receiving Pembrolizumab alone intravenously. Treatments are given as first-line therapy, meaning participants have not received prior systemic treatment for advanced disease. The study compares these treatments to assess their effect on cancer progression and survival. Participants will be closely monitored throughout the study, which includes assessments of progression-free survival over about four years and overall survival over about six years. Researchers will collect tumor samples to confirm PD-L1 and TROP2 status, perform scans to measure tumor response, and evaluate organ function and performance status. Safety and side effects will be tracked to understand treatment tolerability. The entire participation duration may extend up to several years to capture long-term outcomes.

This research aims to evaluate whether lowering blood phosphate levels in people with end-stage kidney disease (ESKD) who are on dialysis can reduce the risk of death or major heart-related events compared to maintaining higher phosphate levels. The study also looks at whether lowering phosphate improves physical health, fatigue, quality of life, patient satisfaction, and itching, as well as whether it is cost-effective. Hyperphosphatemia, or high phosphate in the blood, is common in ESKD and linked to higher death risk, but there is no strong trial evidence that lowering phosphate improves important patient outcomes. Participants will be randomly assigned to one of two groups: an intensive phosphate target group aiming to keep serum phosphate at or below 1.50 mmol/L using phosphate-lowering medications, or a liberal phosphate target group aiming for a higher phosphate range of 2.0 to 2.5 mmol/L. In the liberal group, all phosphate-lowering drugs at baseline will be stopped and only restarted if phosphate rises above 2.5 mmol/L. Medication choice and doses will be based on physicians' and participants' decisions to meet target levels. The trial is multinational and will include 3600 adults on dialysis. During the study, researchers will track major outcomes including cardiovascular death or serious heart and artery events over 5 years. They will also assess physical health, quality of life using the EQ5D-5L questionnaire, fatigue, itching, and overall survival. The study involves monitoring serum phosphate levels and medication use, and measuring cost-effectiveness of the treatment strategies. Participants will be followed closely to understand the safety and impact of the phosphate targets on their health and well-being.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and rare cancer affecting white blood cells, and it is the most common form of non-Hodgkin lymphoma. Follicular lymphoma (FL) is a slower-growing type of this lymphoma. This study aims to evaluate the real-world effectiveness of the investigational drug epcoritamab in adult patients with advanced DLBCL and FL. Around 700 participants will be enrolled across approximately 80 sites in 12 to 20 countries worldwide. Participants will receive epcoritamab as prescribed by their doctors according to the approved treatment guidelines in their country. The study does not add any extra treatments or procedures beyond what their doctors recommend. Participants will be followed for up to about 3 years to observe their responses to the treatment. During the study, participants will attend regular visits at hospitals or clinics as part of their standard care routine. Researchers will track the percentage of participants who achieve an overall response to treatment over the study period. There is no expected additional burden for participants beyond their usual clinical visits and treatments.

Researchers are investigating treatments for patients with localized renal cell carcinoma (RCC) who have undergone nephrectomy, focusing on those at high or intermediate risk of the cancer returning. The study evaluates whether durvalumab alone or combined with tremelimumab can improve disease-free survival or overall survival compared to the current standard of care, which is active monitoring. This phase III multi-arm, multi-stage randomized controlled trial includes patients with specific risk scores, and recruitment of intermediate risk patients will be limited based on time and accrual targets. Participants will be randomly assigned to receive either durvalumab alone, the combination of durvalumab and tremelimumab, or active monitoring. The drugs are given via controlled infusion through a pump into a vein. The trial includes a screening phase and treatment period, with careful monitoring of patients' disease status and side effects throughout the study. During the study, participants will undergo clinical and radiological assessments, including post-operative scans and laboratory tests like blood counts and ECGs. Researchers will track disease-free survival and overall survival over several years, including specific time points up to 20.5 years for some comparisons. Participants will also provide tissue and blood samples for future research. Safety and treatment effects will be closely monitored to understand how the therapies impact long-term outcomes.