Jette

Despite some encouraging data, systemic treatment of CNS metastases from solid tumors remains experimental. Better knowledge on the evolving epidemiology and biology of BM are key elements for the development of new treatment strategies and identification of promising therapeutic targets for new compounds. Further biological findings may help to better understand the heterogeneity between the primary tumor and the CNS metastases and to identify new targets for therapy thus improving patients' outcome. In this context, the Oncodistinct network and the Jules Bordet institute propose to build a multidisciplinary Brain Metastases Clinical Research Platform called BrainStorm. The BrainStorm program will focus on patients with newly diagnosed non-CNS metastatic solid tumors with high risk of developing CNS metastases and will allow building a large clinico pathological database for CNS metastases including ctDNA analyzes from CSF samples. Substudies will be proposed at each time-period with the final objective to develop innovative treatment approaches and strategies.

Researchers are evaluating the efficacy and safety of rilvegostomig compared to pembrolizumab as first-line treatments for patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors have high PD-L1 expression. This Phase III, randomized, double-blind, and global study focuses on participants with stage IV mNSCLC who do not have certain genetic mutations or rearrangements and are eligible for systemic therapy. Participants receive either rilvegostomig or pembrolizumab intravenously on Day 1 of each 21-day cycle. The study compares these two biological treatments given as monotherapy. Both groups will be monitored over time to assess treatment impact and safety. Throughout the study, participants undergo evaluations including tumor measurements by CT or MRI, performance status assessments, and organ function tests. Researchers will measure overall survival and progression-free survival for up to approximately five years. Tumor samples are collected before treatment for central testing, and participants’ health and treatment responses are closely followed during the trial period.

The trial investigates the use of volrustomig in participants with unresected locally advanced head and neck squamous cell carcinoma (LA-HNSCC) who have not shown disease progression after receiving definitive concurrent chemoradiotherapy (cCRT). The study aims to evaluate the efficacy and safety of volrustomig compared to observation in this patient population. Participants have tumors that express PD-L1 and the study is conducted as a Phase III, randomized, open-label, multi-center global trial. Participants are assigned to receive either volrustomig as sequential therapy following cCRT or to an observation group. The treatment period involves monitoring participants who have completed definitive cCRT but remain unresected and have no evidence of metastatic disease. The study focuses on participants with Stage III, IVA, or IVB LA-HNSCC according to AJCC criteria, who have not undergone tumor resection before cCRT and have not been treated with radiotherapy alone. During the study, participants are regularly evaluated for progression-free survival, with follow-up lasting up to approximately 8 years to assess long-term outcomes. Researchers will monitor safety and disease progression closely. The overall participation duration includes screening, treatment or observation, and extended follow-up to capture both efficacy and safety data over time.

The NeoSenti study is a clinical trial exploring whether giving one dose of the immunotherapy drug pembrolizumab before surgery can help improve outcomes for people with high-risk melanoma. Pembrolizumab is a treatment that strengthens the immune system so it can better recognize and attack cancer cells. It is already used after surgery for certain melanoma stages, but this study aims to find out whether giving it earlier-before the sentinel lymph node biopsy-can reduce the chance that melanoma has already spread microscopically. Adults with high-risk primary melanoma who do not show any signs of cancer spread on physical examination or scans may be eligible to participate. Before joining, patients undergo blood tests, a PET/CT scan, an ultrasound of the lymph node area, and a review of their melanoma features. Some patients will also have a Merlin™ genetic test to determine whether their tumor carries a high risk of spreading. Participants who qualify receive a single infusion of pembrolizumab six weeks before their planned surgery. This "pre-surgery" (neoadjuvant) treatment is intended to give the immune system time to attack melanoma cells that may be in the lymph nodes but are too small to detect. About six weeks later, patients undergo surgery, including a sentinel lymph node biopsy-used to check whether melanoma has started to spread-and, if needed, a wide local excision to remove additional tissue around the original melanoma. The results of the surgery determine the next steps. Patients whose cancer is classified as stage IIB, IIC, or III after surgery will continue with standard immunotherapy every six weeks for one year. Patients with stage IB or IIA melanoma will not need additional treatment and will move directly into follow-up care. Regardless of stage, all participants are monitored very closely for five years. This follow-up includes regular physical examinations, blood tests, full-body imaging every four months (PET/CT or whole-body MRI), and optional questionnaires about quality of life and cognitive function. Some patients may also have blood tests that measure tiny amounts of tumor DNA (ctDNA), which might help predict the risk of recurrence.

Researchers are investigating the effectiveness, safety, and tolerability of combining baxdrostat with dapagliflozin compared to dapagliflozin alone in people with chronic kidney disease (CKD) and high blood pressure. This Phase III, international, multicenter, double-blind, placebo-controlled study aims to see if this combination reduces risks such as significant kidney function decline, kidney failure, heart failure events, or cardiovascular death. The study includes a 4-week run-in period where participants not previously treated with SGLT2 inhibitors receive dapagliflozin alone. After this, participants are randomly assigned to receive either baxdrostat plus dapagliflozin or placebo plus dapagliflozin in a double-blinded manner. Study visits occur frequently initially (at 2, 4, 8, 16, 34, and 52 weeks after randomization) and then approximately every 4 months. If participants stop the blinded treatment early, they continue dapagliflozin alone unless specific criteria require its discontinuation. Participants will undergo regular assessments including blood pressure monitoring and laboratory tests related to kidney function and cardiovascular health. The primary outcome measures the reduction in risk of major kidney and heart events over up to 37 months. Even if participants stop the study treatment, they will continue follow-up visits and data collection to ensure comprehensive safety and efficacy evaluation throughout the study duration.

This research aims to evaluate the effectiveness and safety of two different dose schedules of pegozafermin compared to a placebo in adults with metabolic dysfunction-associated steatohepatitis (MASH) who have liver fibrosis at stage F2 or F3. This phase 3 study focuses on improving liver fibrosis and steatohepatitis in this patient group, which involves chronic liver disease associated with metabolic dysfunction. Participants will receive either pegozafermin or a placebo through subcutaneous injections. The study compares two doses of pegozafermin to assess their impact on liver fibrosis and steatohepatitis. The treatment period lasts up to 52 weeks, with outcomes measured at this time point. During the study, participants will be monitored for improvements in liver fibrosis and resolution of steatohepatitis without worsening fibrosis by week 52. Researchers will also track the time until any disease progression occurs, up to 5 years. Throughout the trial, safety and efficacy will be carefully assessed through clinical evaluations and laboratory tests to ensure participant well-being.

Researchers are evaluating HER3-DXd monotherapy in adults with locally advanced unresectable or metastatic solid tumors who have been previously treated with at least one systemic anticancer therapy. This phase 2 proof-of-concept study includes participants with various cancers such as melanoma, squamous cell carcinoma of the head and neck, HER2-negative gastric cancer, ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, prostate cancer, lung cancer, and breast cancer. The study aims to assess the safety, tolerability, efficacy, and pharmacokinetics of HER3-DXd, as well as the relationship between HER3 protein expression in tumor tissue and treatment response. Participants receive HER3-DXd as an intravenous infusion at a dose of 5.6 mg/kg every 21 days on Day 1 of each cycle. The study is organized into multiple cohorts based on tumor type, with treatment continuing until disease progression, unacceptable toxicity, withdrawal, or other specified reasons. HER3 protein expression and its association with treatment outcomes are also investigated. Throughout the study, participants undergo regular assessments including tumor response evaluations according to RECIST v1.1 criteria, radiographic imaging, and laboratory tests. For prostate cancer participants, prostate-specific antigen (PSA) levels are monitored each cycle. Safety and tolerability are closely observed up to approximately 27 months. Participants provide tumor tissue samples either from archival or fresh biopsies before treatment initiation. The overall study duration includes screening, treatment cycles, and follow-up for disease progression or other outcomes.

Cytomegalovirus (CMV) is a common virus that can cause serious illness in people with weakened immune systems, especially those who have received transplants. This research aims to observe how maribavir is used and to evaluate its safety and effectiveness in treating adults with CMV infection after transplant in Belgium, following the country's reimbursement rules. The study is non-interventional, meaning no new treatments are given as part of the study. Instead, it gathers information from adults who are starting maribavir for the first time according to Belgian criteria. Data collection spans up to two years, focusing on participants who have received hematopoietic stem cell or solid organ transplants and are diagnosed with CMV infection or disease. Participants' information will be collected during their routine medical visits and contacts without fixed study visits. Researchers will monitor outcomes such as the effectiveness of maribavir in clearing CMV from the blood within 16 weeks, treatment duration, time to viral clearance up to two years, drug resistance, recurrence of infection, treatment use in daily practice, and any side effects related to treatment during the follow-up period.

Researchers are evaluating the effectiveness of Saruparib (AZD5305) compared to placebo when added to a standard radiation therapy (RT) and androgen deprivation therapy (ADT) regimen in men with high-risk and very high-risk localized or locally advanced prostate cancer who have a BRCA gene mutation. This phase III study aims to assess whether Saruparib can improve metastasis-free survival in this population. About 700 adult male participants will be randomly assigned to receive either Saruparib or placebo along with ADT. There are two groups: Cohort A includes 400 participants with newly diagnosed high-risk or very high-risk prostate cancer treated with primary RT or with high-risk biochemical recurrence after radical prostatectomy receiving salvage RT. Cohort B includes 300 participants with very high-risk locally advanced prostate cancer receiving primary RT combined with ADT and abiraterone. Saruparib and placebo will be given orally, and standard ADT and abiraterone with prednisone/prednisolone will be administered as per the regimen. Participants will be followed for up to about 93 months to monitor metastasis-free survival and overall safety. Assessments include imaging scans like CT, MRI, bone scans, and PSMA-PET to confirm disease status. The study also monitors organ function, performance status, and treatment adherence. An independent committee will review safety and efficacy data throughout the trial to ensure participant well-being and study integrity.

Researchers are evaluating pitolisant in a global, Phase 3 study involving patients with Prader-Willi syndrome who are 6 years of age or older. The study aims to assess whether pitolisant can reduce excessive daytime sleepiness (EDS) and also evaluate its effects on irritability, disruptive behaviors, hyperphagia, and other behavioral problems such as social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech. The study includes up to a 45-day screening and baseline period, followed by a double-blind treatment period where patients are randomly assigned to receive either pitolisant or a placebo once daily. In-person visits during this period occur on Day 29, Day 57, and Day 77. After this, patients may choose to enter an optional open-label extension period with visits on Day 113, Day 260, and Day 441. Follow-up visits occur 15 and 30 days after the final dose in both the double-blind and extension periods. Participants will have assessments to measure the severity of EDS using patient-reported outcomes at the start and end of the double-blind period. Caregivers will complete behavioral evaluations, and researchers will monitor safety and treatment effects throughout. Total participation may last over a year if the optional extension is chosen, with continued follow-up after treatment ends.