Denison

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 whether the drugs retatrutide and tirzepatide can prevent major adverse liver outcomes (MALO) in adults with metabolic dysfunction-associated steatotic liver disease (MASLD) who are at high risk. This Phase 3 trial enrolls about 4,500 adults with MASLD identified by non-invasive tests indicating an increased likelihood of developing serious liver problems. The study aims to understand how these treatments might affect liver health over time compared to a placebo. Participants will be randomly assigned to receive either retatrutide, tirzepatide, or a placebo, all given by subcutaneous injection. The study will last approximately 224 weeks, during which participants may attend 25 to 30 clinic visits for monitoring and assessment. After the main study, eligible participants can join an optional 2-year extension where all will receive either retatrutide or tirzepatide regardless of their original group. Throughout the trial, participants’ liver function and disease progression will be closely monitored through various health assessments. Researchers will track the time to the first major adverse liver event as the main outcome. Safety and health status will be evaluated regularly during clinic visits, ensuring thorough observation over the long study period.

Researchers are conducting a phase 3 open-label, randomized, controlled, multicenter study to compare petosemtamab with investigator's choice monotherapy in patients with head and neck squamous cell carcinoma (HNSCC) who have incurable metastatic or recurrent disease. This study focuses on patients with progressive disease after anti-PD-1 therapy and platinum-containing therapy and aims to evaluate the treatments as second- or third-line options. Participants will receive either petosemtamab or one of the investigator's choice monotherapies, including cetuximab, methotrexate, or docetaxel. The study involves treatment administration under controlled conditions with monitoring for efficacy and safety. The goal is to assess the treatments over time with a focus on response rates and overall survival. During the study, participants will undergo regular assessments including radiologic imaging to measure tumor response, and evaluations of overall survival up to approximately three years. The primary outcomes include objective response rate assessed by blinded independent central review and overall survival. Researchers will monitor patient health, side effects, and treatment effectiveness throughout the study duration.

Researchers are evaluating how CDR132L, a potential new medicine, affects the structure and function of the heart in people living with heart failure who have preserved ejection fraction and left ventricular hypertrophy. This phase 2 study compares different doses of CDR132L with a placebo, which is an inactive treatment. The study aims to understand the safety and effectiveness of CDR132L in reversing heart remodeling in this population. Participants will receive either CDR132L or placebo administered intravenously once every 4 weeks. The study treatment period lasts about 24 weeks, followed by additional assessments leading up to a total study duration of approximately 60 weeks. The study is randomized, double-blind, and placebo-controlled, meaning neither participants nor researchers know who receives the active treatment or placebo during the main phase. During the study, participants will undergo various evaluations including heart imaging via echocardiography to measure heart function and structure, laboratory tests including NT-proBNP levels, and monitoring of heart failure symptoms. The main outcome measured is the change in normalized microRNA-132-3p levels from baseline to week 24. Researchers will also monitor safety and treatment effects throughout the study, which includes regular visits and assessments over the full 60-week period.

Researchers are evaluating the safety of atezolizumab alone or combined with bevacizumab as first-line treatment in adults with unresectable, locally advanced, or metastatic hepatocellular carcinoma (HCC) who have Child-Pugh B7 or B8 liver cirrhosis. This Phase II, open-label study involves participants who have not received prior systemic therapy for their condition and aims to understand treatment safety in this specific population. Participants will be assigned to one of two groups: one receiving atezolizumab plus bevacizumab, and the other receiving atezolizumab alone. Atezolizumab is given as an intravenous infusion at a dose of 1200 mg on the first day of each 21-day cycle. Bevacizumab is administered by intravenous infusion at 15 mg/kg on the same schedule. The study is conducted across multiple centers and includes multiple cohorts to evaluate these treatments separately. During the study, researchers will monitor participants for adverse events from the start until up to approximately 36 months. Assessments include measuring disease status with imaging and clinical evaluations, checking blood tests for liver and kidney function, and monitoring overall health and safety. Participants will be followed closely throughout the treatment and observation periods to gather safety data and evaluate treatment tolerability.

Researchers are evaluating efruxifermin (EFX) in adults aged 18 to 80 who have compensated cirrhosis caused by nonalcoholic steatohepatitis (NASH) or metabolic dysfunction-associated steatohepatitis (MASH). This Phase 3, randomized, double-blind, placebo-controlled study aims to assess the safety and effectiveness of EFX in improving liver health and delaying disease progression in this population. The study focuses on subjects with advanced liver fibrosis (stage 4) but without liver decompensation. Participants are randomly assigned to receive either efruxifermin or a placebo, both administered by subcutaneous injection. The study includes two cohorts: Cohort 1 requires biopsy confirmation of liver fibrosis and specific metabolic features, while Cohort 2 allows biopsy or non-invasive diagnosis. Treatment and observation continue over an extended period to evaluate changes in liver fibrosis and clinical events. During the study, researchers will monitor the time until significant clinical events such as disease progression or liver decompensation occur, with a follow-up of up to five years. For Cohort 1, the proportion of participants showing improvement in fibrosis without worsening steatohepatitis will be assessed at 96 weeks. Participants will undergo regular evaluations including clinical assessments and laboratory tests to track liver function and safety throughout the study period.

Researchers are investigating the safety and effectiveness of efruxifermin in people with non-cirrhotic nonalcoholic steatohepatitis (NASH) or metabolic dysfunction-associated steatohepatitis (MASH) who have moderate to advanced liver fibrosis (stage 2 or 3). This Phase 3 study is randomized, double-blind, and placebo-controlled, enrolling a total of 1650 participants in two groups to evaluate treatment outcomes. Participants will receive either efruxifermin or a placebo by subcutaneous injection. The study involves two cohorts, with Cohort 1 including patients who have biopsy-confirmed NASH or MASH and specific liver fibrosis and activity scores. The treatment period and detailed dosing schedules are not provided but the study compares the effects of the active drug against placebo. During the study, participants will be monitored for improvement in liver disease status, including resolution of NASH/MASH and at least a one-stage improvement in liver fibrosis after 52 weeks for Cohort 1. Long-term outcomes such as event-free survival will be observed over 240 weeks. Safety and efficacy assessments will be conducted throughout the study period, including evaluations of liver histology and metabolic health.

Researchers are evaluating the safety and effects of a medicine called disitamab vedotin for adults with advanced breast cancer that is hard to treat and has spread in the body. This study focuses on participants whose tumors express HER2 and who have received previous treatments for their advanced breast cancer. The goal is to understand how well this medicine works and its safety in these patients through a Phase 1b/2 open-label study. All participants will receive disitamab vedotin intravenously (IV) once every two weeks at the study clinic. They will continue the treatment until they or their doctor decide to stop, which could be due to cancer progression, side effects, or personal choice. During treatment, study visits occur every two weeks. After stopping treatment, participants will have follow-up visits about every six weeks, and later follow-up phone calls approximately every twelve weeks. Participants will undergo evaluations including assessments of their cancer response by the study doctors, following recognized criteria. The study team will monitor the participants for up to about two years or until their disease progresses or they pass away. This includes safety monitoring and collecting information about the medicine’s effects to determine its safety and effectiveness.

Researchers are evaluating how well elritercept (TAK-226, KER-050) works in reducing the need for red blood cell (RBC) transfusions in adults with very low, low, or intermediate risk myelodysplastic syndromes (MDS) who require regular blood transfusions. The study is a Phase 3, double-blind, randomized, placebo-controlled trial that also aims to assess the safety and tolerability of elritercept over both short and longer periods, including in adults with high transfusion needs. Participants will be randomly assigned in a 2:1 ratio to receive either elritercept or a matching placebo by subcutaneous injection every 4 weeks. The study includes a Primary Phase lasting 24 weeks and a Secondary Phase lasting an additional 24 weeks, during which participants continue the same treatment. Following these phases, an Extension Phase allows eligible participants to continue treatment until discontinuation or study unblinding. Study visits occur every 2 weeks during the first 6 cycles and every 4 weeks thereafter. Treatment continuation depends on meeting disease assessment criteria every 24 weeks. Participants will undergo various assessments including bone marrow aspirates, transfusion evaluations, and disease status checks throughout the study. Safety follow-up lasts for 8 weeks after the last dose, with visits every 4 weeks during this time. Afterward, long-term follow-up occurs quarterly for up to 5 years or until withdrawal, death, loss to follow-up, or study closure. The main outcome measured is the percentage of participants achieving transfusion independence for at least 8 weeks during the first 24 weeks of treatment.

Researchers are evaluating the efficacy and safety of belimumab compared to a placebo, alongside standard therapy, for adults with systemic sclerosis associated interstitial lung disease (SSc-ILD). This Phase 2/3 randomized, double-blind study aims to assess how belimumab affects lung function and other disease symptoms such as skin thickening and fatigue, which impact quality of life. Participants will receive either belimumab or placebo administered subcutaneously. The study focuses on those diagnosed with diffuse cutaneous systemic sclerosis and active or progressive disease. Treatment is given under blinded conditions, and participants must be capable of self-administering the medication or have a caregiver to assist. During the study, lung function will be monitored by measuring changes in forced vital capacity (FVC) from baseline to Week 52. Researchers will also assess skin involvement and general symptoms. Safety and tolerability will be closely followed throughout the trial, which includes screening and regular assessments to evaluate treatment effects and participant well-being.