Hamburg

Researchers are evaluating the safety and effectiveness of elenestinib BLU-263 combined with symptom directed therapy SDT compared to placebo plus SDT in adults with indolent systemic mastocytosis ISM whose symptoms are not well controlled by SDT alone. This randomized, double-blind, placebo-controlled Phase 23 study includes multiple parts to assess different doses and durations of elenestinib treatment, including an open-label extension for participants finishing earlier phases. The study also enrolls participants who have previously received an approved selective KIT inhibitor and includes pharmacokinetic groups. Participants receive oral elenestinib or placebo once daily alongside SDT, which is personalized based on individual symptom management needs. Part 1 focuses on short-term treatment lasting up to 12 weeks, while Part 2 extends treatment to approximately 48 weeks. Part 3 and other parts allow treatment for up to about 5 years. The study monitors participants through these phases to evaluate how elenestinib affects symptoms, disease markers, and safety over time. During the study, participants undergo regular assessments of symptoms using the ISM-Symptom Assessment Form ISM-SAF, laboratory tests including serum tryptase and KIT D816V allele levels, bone marrow evaluations, and quality of life measures. Researchers track adverse events and changes in disease-related factors at various points up to 5 years. This thorough monitoring helps measure treatment effects and safety over both short and long-term periods, with total participation lasting several years depending on the study part.

Researchers are evaluating the combination of CGT9486 and sunitinib compared to sunitinib alone in patients with locally advanced, unresectable, or metastatic Gastrointestinal Stromal Tumors GIST. This Phase 3, open-label international trial involves multiple parts, including dose confirmation, drug interaction assessments, and efficacy comparisons. The study also includes substudies focusing on drug-drug interaction potential and first-line treatment in patients with specific genetic mutations KIT exon 9. Approximately 482 patients will participate across these parts.

This trial investigates treatment options for patients with microsatellite stable MSS or proficient mismatch repair pMMR metastatic colorectal cancer who do not have active liver metastases. It is a phase II, prospective, randomized, open-label study conducted across multiple centers. The study aims to evaluate the effectiveness of Fruquintinib combined with Tislelizumab compared to a control treatment in this specific patient group. Participants will be randomly assigned to one of two groups. One group will receive Fruquintinib orally once daily for 21 days in a 28-day cycle along with Tislelizumab given intravenously every 42 days. The other group will receive Trifluridinetipiracil orally twice daily on specific days of a 28-day cycle plus Bevacizumab intravenously every 14 days. Treatment will continue until disease progression, unacceptable side effects, patient choice, or a maximum of 15 months. During the study, patients will undergo regular assessments including imaging scans to monitor disease status, evaluations of side effects, and quality of life measures. Follow-up will continue for up to 18 months after the last patient begins treatment or until death, withdrawal, or loss to follow-up. Researchers will primarily measure the efficacy of the Fruquintinib and Tislelizumab combination, along with overall survival, response rates, safety, and quality of life.

Chronic kidney disease CKD affects over 800 million people worldwide and leads to significant health challenges, including multiple secondary diseases, frequent hospital visits, and high costs. Recent advances have identified promising drugs like sodium-glucose co-transporter 2 inhibitors, finerenone, and semaglutide that may slow CKD progression. This study aims to evaluate whether a biomarker-guided treatment approach can better reduce kidney function decline compared to standard care in CKD patients with albuminuria. This prospective, randomized, open-label study plans to enroll 125 participants with CKD and albuminuria who will be randomly assigned to either a biomarker-targeted treatment group or a standard care group. In the treatment group, medications such as dapagliflozin, finerenone, and semaglutide will be added stepwise based on urinary biomarkers UACR and UEGF and individual response. After about four weeks on each drugs maximum tolerated dose, biomarker levels will be reassessed to decide whether to continue, switch, or add treatments. Participants will undergo regular evaluations of kidney function through estimated glomerular filtration rate eGFR and urinary biomarkers throughout the study, which lasts over two years. The main outcome measured is the change in eGFR slope from week 26 to week 104. Additional assessments include changes in eGFR and UACR from baseline to week 104 or 112. Safety and effectiveness of the biomarker-guided approach will be monitored carefully during the trial.

Researchers are evaluating the safety and effectiveness of the VCFix Spinal System, a medical device designed to treat specific spinal fractures called vertebral compression fractures VCFs in adults aged 21 to 85 years. This study involves up to 8 hospitals in Europe and aims to assess how well the device works and how safe it is for patients with these fractures. The study compares two groups one receiving the VCFix implant with bone cement and the other without cement. Participants will receive the VCFix device implant either with or without the use of PMMA bone cement, according to their assigned study group. The device features in situ adjustment to realign vertebrae, a titanium structure allowing natural bone healing, and the potential to stabilize severe fractures through a pedicle screw component. Treatment will follow intended use guidelines, and researchers will monitor outcomes including pain reduction, function improvement, and device-related complications. During the study, participants will be assessed for changes in back pain and daily functioning at 6 months compared to before treatment. Additional measures include vertebral height restoration, spinal angle improvements, and health-related quality of life at various time points up to 24 months. Safety will be monitored through serious adverse device effects during the first month and adverse events up to two years. The total participation duration extends through follow-up assessments to evaluate both effectiveness and safety.

Researchers are investigating new treatments for advanced renal cell carcinoma RCC that has returned after prior therapy. The study aims to find out if the combination of belzutifan and zanzalintinib can help people with recurrent advanced RCC live longer without their cancer worsening compared to the drug cabozantinib. This is a phase 3 randomized trial evaluating these treatments in participants who have experienced recurrence during or after prior anti-PD-1L1 therapy. Participants are randomly assigned to receive either belzutifan plus zanzalintinib taken orally once daily or cabozantinib taken orally once daily. They continue their assigned treatment until certain reasons require stopping the study intervention. The study compares the effects of these treatments on cancer progression and survival among people with advanced RCC who have had disease recurrence after adjuvant therapy. During the study, participants will be regularly monitored for progression-free survival and overall survival for up to about 73 months. Researchers will also assess tumor response, duration of response, adverse events, and quality of life using questionnaires over approximately 25 months. The study involves ongoing evaluations to understand how these treatments affect symptoms, functioning, and overall health during long-term follow-up.

Researchers are studying treatments for locally advanced or metastatic colorectal cancer mCRC that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This trial aims to evaluate if adding the targeted therapies calderasib and cetuximab to the standard chemotherapy regimen mFOLFOX6 can provide better outcomes compared to mFOLFOX6 with or without bevacizumab. The study focuses on the safety and tolerability of these combinations and whether they can help people live longer without their cancer growing or spreading. Participants will be assigned to one of two groups. One group will receive calderasib orally, cetuximab every two weeks, and mFOLFOX6 chemotherapy including oxaliplatin, leucovorin or levofolinate calcium, and 5-fluorouracil every two weeks. The other group will receive mFOLFOX6 chemotherapy with or without bevacizumab every two weeks, based on the investigators decision. Treatments will continue until certain stopping criteria are met. During the study, participants will be monitored for side effects and treatment tolerance, with regular assessments of cancer progression. Researchers will measure outcomes such as dose-limiting toxicities, adverse events, progression-free survival, and overall survival. Quality of life will also be evaluated through questionnaires. The study may last up to several years, with monitoring continuing for safety and effectiveness throughout the treatment period and follow-up.

Researchers are studying metastatic castration-resistant prostate cancer mCRPC to find new treatment options. This trial evaluates if the study medicine ifinatamab deruxtecan I-DXd or MK-2400 helps people live longer overall and experience slower cancer growth or spread compared to chemotherapy. The study is a Phase 3 trial comparing I-DXd with standard chemotherapy for mCRPC patients. Participants are randomly assigned to receive either I-DXd at 12 mgkg every 3 weeks through intravenous infusion or docetaxel chemotherapy at 75 mgm2 every 3 weeks combined with daily prednisone pills. Treatment continues until the disease progresses, unacceptable side effects occur, or treatment is stopped for other reasons. Premedication is given before each dose of I-DXd to help prevent nausea and vomiting. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess overall survival and radiographic progression-free survival for up to about 36 months. Additional measures include response rates, time to pain progression, PSA progression, and adverse events. The study tracks safety, treatment effects, and quality of life over a long follow-up period to better understand the potential benefits and risks of I-DXd compared to chemotherapy.

This research investigates treatments for metastatic castration-resistant prostate cancer mCRPC focusing on a drug called ifinatamab deruxtecan I-DXd. The study aims to assess the safety, how well participants tolerate the treatments, and appropriate dosing levels of I-DXd alone or combined with other therapies. Researchers will also monitor participants prostate specific antigen PSA levels during treatment to understand its effects. Participants are assigned to one of several treatment groups. One group receives docetaxel every three weeks for up to 10 cycles. Other groups receive I-DXd alone or combined with either opevesostat or androgen receptor pathway inhibitors such as abiraterone acetate or enzalutamide. I-DXd is given every three weeks until unacceptable side effects, disease progression, death, or withdrawal, while the other drugs continue until specific discontinuation criteria are met. Premedication is required before each I-DXd dose to prevent nausea and vomiting. Throughout the study, participants undergo various assessments including monitoring of dose-limiting toxicities, adverse events, and PSA response rates. Researchers also track objective response rates, progression-free survival, overall survival, and other clinical outcomes over up to approximately 54 months. The study involves regular evaluations to assess safety and treatment effects until study completion.

Researchers are investigating if intismeran autogene combined with pembrolizumab can prevent advanced melanoma from growing or spreading. Advanced melanoma is skin cancer that has spread to other parts of the body and cannot be removed with surgery. The study aims to see if people receiving intismeran autogene with pembrolizumab live longer without their cancer worsening than those receiving placebo with pembrolizumab. This is a phase 2 clinical trial evaluating these treatments in people with first-line advanced melanoma. Participants will receive either intismeran autogene or placebo via intramuscular injection every 3 weeks for up to 9 doses about 27 weeks. All participants will also receive pembrolizumab by intravenous infusion every 6 weeks for up to 17 doses, totaling around 2 years of treatment or until their disease progresses or they stop the treatment. The study compares the experimental combination to a placebo plus pembrolizumab to better understand the effects of intismeran autogene. During the study, participants will have regular assessments to measure how long they live without the cancer growing or spreading, as well as overall response and survival up to 6 years. Researchers will monitor side effects and reasons for stopping therapy for up to 2 years. Participants will undergo scans and tumor tissue analysis for biomarker studies. The trial includes a randomized design with triple masking and aims to enroll adults aged 18 and older with advanced melanoma.