Hamburg

Researchers are evaluating the safety and effectiveness of elenestinib (BLU-263) combined with symptom-directed therapy (SDT) compared to placebo plus SDT in people with indolent systemic mastocytosis (ISM) whose symptoms are not well controlled by SDT alone. This Phase 2/3 randomized, double-blind, placebo-controlled study includes participants with ISM and smoldering systemic mastocytosis, and also involves groups for pharmacokinetic studies and participants who previously received a selective KIT inhibitor. The study is divided into multiple parts. Parts 1 and 2 enroll participants with ISM who will receive either elenestinib oral tablets or placebo alongside their symptom-directed therapy. Participants from Part 2 may continue into Part 3, which is an open-label extension where all receive elenestinib. Part K enrolls participants with ISM who have prior experience with selective KIT inhibitors. The study tracks treatment effects and safety over time. Participants will be monitored for up to 5 years, with assessments including the number of treatment-emergent adverse events, changes in symptom scores measured by the ISM-Symptom in Assessment Form, and overall safety monitoring. Evaluations occur at baseline, 13 weeks, 49 weeks, and throughout the long-term follow-up. The study also includes detailed tracking of symptom control and adverse events to evaluate the impact of treatment on participants' health and quality of life.

Researchers are conducting a phase II, multicenter, open-label trial to investigate the combination of Fruquintinib and Tislelizumab in patients with microsatellite stable (MSS) or proficient mismatch repair (pMMR) metastatic colorectal cancer who do not have active liver metastases. The study aims to evaluate the effectiveness of this combination in comparison to a control treatment for this specific group of patients. Participants will be randomly assigned to one of two treatment groups. The experimental group will receive oral Fruquintinib (5 mg daily for 21 days in each 28-day cycle) along with intravenous Tislelizumab (400 mg every 42 days). The control group will be treated with oral Trifluridine/tipiracil (35 mg/m2 twice daily on days 1-5 and 8-12 of each 28-day cycle) plus intravenous Bevacizumab (5 mg/kg every 14 days). Treatment continues until disease progression, unacceptable side effects, patient choice, or a maximum of 15 months. During the study, patients will undergo regular assessments including imaging to monitor disease status and safety evaluations. Follow-up will continue for up to 18 months after the last patient enrolls or until death, withdrawal, or loss to follow-up. The main outcome measure is the efficacy of Fruquintinib combined with Tislelizumab in this patient population over a 54-month period.

Chronic kidney disease (CKD) affects over 800 million people worldwide and leads to high health burdens, multiple related diseases, frequent doctor visits, hospitalizations, and significant healthcare costs. New drug treatments like sodium-glucose co-transporter 2 inhibitors, finerenone, and semaglutide have shown promise in lowering albuminuria and protecting kidney function, but the best way to combine or sequence these treatments is unclear. This study aims to evaluate if using biomarkers to guide treatment choices can better slow kidney function decline compared to standard care in people with CKD and albuminuria. This is a Phase 4, prospective, randomized, open-label, parallel-group, multicenter study enrolling 125 adults with CKD who have an estimated glomerular filtration rate (eGFR) of at least 25 mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) between 100 and 5000 mg/g. Participants are randomly assigned to either a biomarker-targeted treatment approach or standard care. In the biomarker group, patients start treatment with one of three drugs (dapagliflozin, finerenone, or semaglutide) and after about four weeks on the maximum tolerated dose, urinary biomarkers are measured to decide whether to continue, switch, or add another drug. This process can repeat up to three drugs based on biomarker responses. Participants will be monitored for changes in kidney function primarily by measuring the chronic eGFR slope from week 26 to 104. Throughout the study, urine samples for biomarkers and clinical assessments will be conducted to track treatment effects. Safety and adherence will be evaluated, and the study duration includes regular follow-ups to assess long-term impacts of the biomarker-guided treatment compared to standard care.

Researchers are evaluating the safety and effectiveness of the VCFix Spinal System for treating Vertebral Compression Fractures. The study aims to reduce pain related to vertebral fractures and improve physical function and mobility, while ensuring no serious adverse events related to the device or procedure occur. This clinical investigation focuses on a device designed to realign and stabilize fractured vertebrae with potential benefits over traditional bone cement methods. The VCFix Spinal System is a device that can be adjusted in place to restore vertebral height and correct spinal alignment. It features a titanium structure that supports natural bone healing and may provide better stability without the use of bone cement. The device also connects the front and back parts of the spine to improve load distribution and support more severe fractures. Participants receive this device in a stand-alone configuration as part of the treatment. Participants will be monitored for changes in pain intensity using an 11-point pain scale and physical function using the Oswestry Disability Index over 6 months. Safety is closely observed, particularly for serious adverse device effects within the first month after treatment. The study includes assessments of pain, function, and adverse events to evaluate the overall impact of the VCFix system. The study involves adults aged 21 to 85 with specific types of vertebral fractures suitable for this treatment.

Researchers are studying advanced renal cell carcinoma (RCC) that has returned after prior adjuvant therapy. The trial aims to find out if treatment with belzutifan and zanzalintinib helps patients live longer and delays disease progression compared to treatment with cabozantinib. This is a Phase 3 randomized study focusing on participants with recurrent advanced RCC who have previously received anti-PD-1/L1 therapy. Participants are randomly assigned to receive one of two oral drug regimens: either belzutifan combined with zanzalintinib, both taken once daily, or cabozantinib alone, also taken once daily. The study compares these treatments to assess their effects on disease control and overall survival. During the study, participants will be monitored for progression-free survival and overall survival for up to approximately 73 months. Researchers will evaluate how well the cancer responds to treatment and track any changes in health status over time. Safety and effectiveness of the treatments will be closely followed throughout the study period.

Researchers are evaluating new treatment options for adults with locally advanced or metastatic colorectal cancer that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This study compares the safety and effectiveness of adding calderasib and cetuximab, both targeted therapies, to a standard chemotherapy regimen called mFOLFOX6. The goal is to see if this combination can help patients live longer without their cancer growing or spreading compared to current treatments that may include mFOLFOX6 with or without bevacizumab. The study has two parts. It involves treatment with calderasib taken as an oral tablet, cetuximab given according to standard procedures, and mFOLFOX6 chemotherapy combining oxaliplatin, leucovorin/levofolinate calcium, and 5-fluorouracil. Some participants may receive bevacizumab or a bevacizumab biosimilar as part of the comparison. The treatments are given following approved dosing schedules. This design allows researchers to assess the safety and tolerability of these drug combinations in treating this type of colorectal cancer with the KRAS G12C mutation. Participants will be monitored for side effects, treatment tolerability, and cancer progression over a period that may last up to about 44 months. Researchers will track outcomes such as how many participants experience dose-limiting toxicities or adverse events, how many stop treatment due to side effects, and progression-free survival time. Assessments include health evaluations, laboratory tests, and imaging to observe cancer status. This long-term follow-up aims to understand both safety and effectiveness of the treatment combinations.

Researchers are evaluating a new treatment called ifinatamab deruxtecan (I-DXd) for men with metastatic castration-resistant prostate cancer (mCRPC). This study compares I-DXd to chemotherapy to see if it helps people live longer overall and live longer without their cancer worsening. It is a Phase 3, open-label trial focused on patients who have progressed on prior therapies and have evidence of metastatic disease. Participants receive either I-DXd through an intravenous infusion every 3 weeks or docetaxel chemotherapy administered every 3 weeks. Prednisone tablets are also given daily as part of the treatment plan. Before each I-DXd dose, premedication is provided to help prevent nausea and vomiting using a combination of drugs such as corticosteroids and anti-nausea medicines. Treatment continues until disease progression, unacceptable side effects, or other reasons to stop. During the study, researchers monitor overall survival and how long patients live without their cancer progressing, for up to about 36 months. Participants undergo tumor tissue collection, scans, and assessments to track disease status and side effects. Safety is closely watched throughout treatment. The study includes men aged 18 and older with confirmed prostate cancer and metastatic disease who have previously received certain hormone therapies but no prior taxane chemotherapy for mCRPC.

Researchers are evaluating the safety and effectiveness of ifinatamab deruxtecan (I-DXd) alone or combined with other treatments in people with metastatic castration-resistant prostate cancer (mCRPC). This study aims to understand how well patients tolerate the treatment, find a safe dose for combining I-DXd with other drugs, and measure prostate-specific antigen (PSA) levels during treatment. The study is part of a larger master screening protocol and includes patients with confirmed prostate adenocarcinoma who have progressive disease despite prior therapies. Participants receive treatments including I-DXd given through intravenous infusion, sometimes combined with other drugs such as docetaxel (IV), MK-5684, abiraterone, or enzalutamide (all oral). Before each I-DXd dose, patients take premedication to prevent nausea and vomiting. The study includes both a safety lead-in phase and an efficacy phase, with ongoing monitoring for side effects and tolerability. The combination therapies are carefully dosed and scheduled according to the study protocol. During the study, participants undergo regular assessments to monitor side effects, measure PSA response, and track any dose-limiting toxicities. Safety is closely followed, particularly during the first 21 days for combination treatments, and throughout up to 54 months for long-term outcomes. Researchers also observe if participants discontinue treatment due to adverse events. The study requires ongoing visits and evaluations to ensure participant health and collect data on treatment effects over time.

Researchers are studying intismeran autogene combined with pembrolizumab to see if it can stop advanced melanoma, a type of skin cancer that has spread and cannot be removed by surgery, from growing or spreading. This Phase 2 study compares this combination to pembrolizumab with a placebo, aiming to find out if the new treatment helps people live longer without cancer progression. Immunotherapy, which helps the immune system fight cancer, is a standard treatment for advanced melanoma, and intismeran autogene is designed to boost the immune response against a person's specific cancer. Participants receive either intismeran autogene or a placebo through intramuscular injection, along with pembrolizumab given as an intravenous infusion. The study is randomized, double-blind, and controlled, meaning neither participants nor researchers know who gets the active treatment or placebo. This design helps to better understand the effects of intismeran autogene when combined with pembrolizumab. During the study, researchers will monitor participants for up to about 36 months to measure progression-free survival, which means the length of time participants live without the cancer worsening. Assessments include imaging scans to track tumor changes, tumor tissue collection for biomarker analysis, and documentation of any side effects. Participants may also have their mutation status checked and will be observed for safety throughout the study period.

Researchers are studying the safety and early effectiveness of a new cell therapy called CLDN6 CAR-T, with or without an RNA-based vaccine, in patients who have CLDN6-positive advanced solid tumors that have returned or not responded to prior treatments. This Phase I, first-in-human, open-label trial involves multiple sites and focuses on patients with tumors expressing the CLDN6 protein at a high level. The study aims to find the best dose of these therapies and gather initial evidence of their activity against these difficult cancers. The trial has two main parts. The first part tests increasing doses of CLDN6 CAR-T cells made using manual and automated processes to determine the maximum tolerated dose or recommended dose for future studies. The second part adds the CLDN6 RNA-based vaccine to the CAR-T cells, exploring dose levels to optimize treatment effects. The CAR-T cells and RNA vaccines are given through intravenous infusions or injections at scheduled times. An optional dose decrease may be evaluated to further assess safety and effectiveness. Participants will be followed for up to 25 months in the main trial, with ongoing assessments of side effects, dose adjustments, and treatment tolerability. After the main study, patients may join a long-term follow-up period lasting up to 15 years to monitor delayed effects and long-term outcomes. Researchers will collect medical information through scans, lab tests, and clinical evaluations to measure safety events, including serious and dose-limiting toxicities, as well as treatment responses over time.