Mezitli

This trial investigates the safety and effectiveness of rilvegostomig combined with fluoropyrimidine and trastuzumab deruxtecan (T-DXd) compared to trastuzumab, chemotherapy, and pembrolizumab in adults with HER2-positive locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 with a combined positive score of 1 or higher. Additionally, rilvegostomig combined with trastuzumab and chemotherapy is studied separately to understand each component's contribution. This Phase 2, randomized, open-label, global study is conducted at 200-250 sites in about 25 countries. Participants are randomly assigned to one of three arms: Arm A receives rilvegostomig, fluoropyrimidine, and T-DXd; Arm B receives trastuzumab, chemotherapy, and pembrolizumab; Arm C receives rilvegostomig, trastuzumab, and chemotherapy. Treatments are administered mostly by intravenous infusion every three weeks, with capecitabine given orally twice daily. The study compares these treatment regimens to evaluate their effects on the cancer. Throughout the study, participants undergo assessments including tumor measurements, organ function tests, and heart function evaluation to ensure safety and monitor disease progression. The main outcomes measured are progression-free survival and overall survival for up to approximately six years. Researchers will also monitor adverse events and overall health status during and after treatment.

Researchers are studying an experimental drug called odronextamab in combination with lenalidomide for adults with relapsed or refractory follicular lymphoma (FL) or marginal zone lymphoma (MZL), which are subtypes of Non-Hodgkin's lymphoma. This Phase 3 study has two parts: Part 1 focuses on the safety and tolerability of this drug combination and determining the appropriate odronextamab dose, while Part 2 compares the effectiveness of this combination to the current standard treatment of rituximab plus lenalidomide. The study also explores side effects, drug levels in the blood, antibody development against the study drug, and impacts on quality of life and daily activities. Participants receive either odronextamab plus lenalidomide or rituximab plus lenalidomide according to the study protocol. Part 1 is not randomized, focusing on safety and dose finding, while Part 2 is randomized and controlled to assess efficacy and safety. Treatments are administered per protocol guidelines during these study phases. During the study, participants undergo regular evaluations including imaging scans to measure disease, blood tests, and monitoring for side effects up to two years. The main outcomes measured include dose-limiting toxicities within 35 days, treatment-emergent adverse events over two years, and progression-free survival over five years. Participants are also monitored for quality of life and ability to perform daily activities throughout the trial duration.

Researchers are evaluating an experimental drug called odronextamab for adults with previously untreated follicular lymphoma, a type of non-Hodgkin lymphoma. This Phase 3 study aims to assess the safety, tolerability, and effectiveness of odronextamab alone and compared to the current standard treatments, including rituximab combined with different types of chemotherapy. The study also examines side effects, drug levels in the blood, antibody responses against odronextamab, and the impact on quality of life and daily activities. The study consists of two parts: Part 1 is non-randomized and focuses on the safety and tolerability of odronextamab given alone. Part 2 is randomized and controlled, comparing odronextamab to rituximab combined with chemotherapy regimens such as CHOP, CVP, or Bendamustine-containing therapies. All treatments are administered according to the study protocol. Participants receive these treatments to evaluate how well odronextamab works versus standard care. Participants will undergo various assessments including imaging scans like CT or MRI to measure disease, blood tests to monitor bone marrow and liver function, and evaluations of side effects up to two years. Researchers will track dose-limiting toxicities within 35 days and assess complete response rates over 30 months. Safety and side effects will be monitored continuously, and quality of life will also be evaluated. The total length of participation depends on treatment and follow-up schedules defined in the protocol.

Researchers are evaluating the efficacy and safety of combining gedatolisib with fulvestrant and CDK4/6 inhibitors for treating patients with locally advanced or metastatic hormone receptor positive, HER2-negative (HR+/HER2-) advanced breast cancer. This Phase 3, open-label, randomized trial focuses on patients whose cancer progressed during or within 12 months of adjuvant endocrine therapy and who have not received prior systemic therapy for advanced breast cancer. The trial separates participants into groups based on PIK3CA mutation status and compares the investigational treatment to standard care. Participants receive either the investigational treatment of intravenous gedatolisib once weekly for three weeks followed by a week off, combined with oral palbociclib or ribociclib taken on days 1-21 of each 28-day cycle plus intramuscular fulvestrant every 2 weeks during the first cycle and then every 4 weeks, or the standard-of-care treatment of oral palbociclib or ribociclib with intramuscular fulvestrant on the same schedules without gedatolisib. The study includes a safety run-in phase to determine dosing of gedatolisib with ribociclib before randomization. Throughout the study, participants will undergo assessments to monitor progression-free survival, which is measured from randomization until death from any cause for up to approximately 48 months. Evaluations include tumor tissue or liquid biopsies for PIK3CA status, imaging to assess measurable disease, and monitoring of bone marrow, liver, kidney, and coagulation functions. Safety and efficacy are closely followed with ongoing clinical evaluations, and participants must have an expected life expectancy greater than six months for enrollment.

Researchers are evaluating the safety and effectiveness of combining trastuzumab deruxtecan (T-DXd) with rilvegostomig compared to standard treatments in patients with advanced HER2-expressing biliary tract cancer who have not received prior therapy. This phase 3 study focuses on patients with locally advanced or metastatic disease and aims to measure overall survival and safety outcomes. Participants will receive one of the following treatments: the experimental combination of T-DXd and rilvegostomig by intravenous infusion, T-DXd alone, or a standard care regimen consisting of gemcitabine, cisplatin, and durvalumab given intravenously. The study includes a safety run-in period to assess tolerability of the combination, followed by a randomized phase where patients receive assigned treatments. Each treatment cycle lasts 21 days. During the study, participants will be closely monitored through clinical assessments, laboratory tests, and imaging to evaluate tumor response and safety. Researchers will track overall survival from the time of treatment initiation until death from any cause, with follow-up estimated up to 50 months. Additional assessments include performance status, organ function, and tumor tissue analysis to confirm HER2 expression and other markers. Safety and side effects will be continuously evaluated throughout the study.

Researchers are evaluating the effectiveness and safety of givinostat compared to hydroxyurea in patients with high-risk polycythemia vera (PV) who have the JAK2V617F mutation. PV is a chronic condition that increases the risk of blood clots and can progress to more severe diseases like myelofibrosis or leukemia. High-risk patients are those aged 60 or older or those with a history of blood clots. Current treatments often do not fully control symptoms or long-term risks in these patients. The study involves two treatment groups receiving oral medications: givinostat or hydroxyurea. Dosages of both drugs are adjusted based on side effects or how well the treatment is working, aiming for an optimal dose. The core treatment phase is a pivotal phase 3 trial designed to show whether givinostat is more effective than hydroxyurea. Patients who finish this phase may continue receiving givinostat in an extended treatment phase to collect additional long-term safety and efficacy data. Participants will be assessed regularly, including monitoring blood counts and clinical response up to week 48. The main outcome measured is the proportion of patients who achieve a response by week 48, evaluated between weeks 25 and 48. Safety monitoring includes heart rhythm checks and other clinical evaluations. Eligible patients must meet specific criteria related to diagnosis, risk factors, and treatment needs, and those who complete the core phase successfully may enter the extended phase for further observation.