Mezitli

Researchers are assessing the effectiveness and safety of rilvegostomig combined with fluoropyrimidine and trastuzumab deruxtecan 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 CPS 1. The study also evaluates rilvegostomig combined with trastuzumab and chemotherapy to understand the contribution of each treatment component. This is a Phase 2, randomized, open-label, global, multicenter trial sponsored by AstraZeneca. Participants are divided into three groups Arm A receives T-DXd, rilvegostomig, and fluoropyrimidine capecitabine or 5-FU Arm B receives pembrolizumab, trastuzumab, and chemotherapy either 5-FU plus cisplatin or capecitabine plus oxaliplatin Arm C receives rilvegostomig, trastuzumab, and chemotherapy 5-FU plus cisplatin or capecitabine plus oxaliplatin. Treatments are given by intravenous infusion every three weeks or oral administration twice daily for capecitabine. This setup allows comparison of different combinations to evaluate each drugs role. During the study, participants will be monitored for progression-free survival and overall survival up to about six years. Researchers will also assess response rates, duration of response, adverse events, pharmacokinetics, immunogenicity, and quality-of-life factors like eating difficulties and side-effect burden. The study involves regular assessments including tumor measurements and laboratory tests. Participation may last several years, with safety and efficacy closely followed throughout this time.

Researchers are evaluating an experimental drug called odronextamab combined with chemotherapy in adults with Diffuse Large B-cell Lymphoma DLBCL, including those who have not been treated before as well as those with relapsed or refractory disease. The study aims to assess the safety, tolerability, and dosing schedule of odronextamab with chemotherapy, and to compare its effectiveness against the current standard treatment of rituximab combined with chemotherapy. Additional goals include understanding side effects, drug levels in the blood, immune responses to the drug, and impact on quality of life and daily activities. The study consists of three parts Part 1A involves dose escalation to find a safe dose, Part 1B explores two dosing regimens of odronextamab combined with chemotherapy, and Part 2 randomly assigns participants to receive either odronextamab plus chemotherapy Odro-CHOP or rituximab plus chemotherapy R-CHOP. Odronextamab and rituximab are given by intravenous infusion, with chemotherapy drugs including cyclophosphamide, doxorubicin, vincristine, and prednisone or prednisolone administered as part of the treatment regimen. Participants will be closely monitored throughout the study for side effects, disease progression, and response to treatment. Assessments include measuring dose limiting toxicities, treatment-emergent adverse events, progression free survival, quality of life questionnaires, and blood tests for drug levels and antibodies. The study follows participants for up to 5 years to track long-term outcomes and safety, with regular visits and evaluations scheduled during and after treatment.

Researchers are evaluating an experimental drug called odronextamab combined with lenalidomide in adults who have relapsed or refractory follicular lymphoma FL or marginal zone lymphoma MZL, which are subtypes of Non-Hodgkins lymphoma. The study aims to assess the safety, tolerability, and proper dosing of this new combination and compare its effectiveness to the current standard treatment of rituximab combined with lenalidomide. The research also explores side effects, drug levels in the blood, immune responses to the drug, and impacts on quality of life and daily functioning. The study has two parts Part 1 is a safety phase where all participants receive odronextamab plus lenalidomide to determine the appropriate dose. Part 2 is randomized and compares two groupsone receiving odronextamab with lenalidomide, and the other receiving rituximab with lenalidomide followed by lenalidomide alone. Participants receive these treatments according to the study protocol during these phases. Throughout the study, participants will undergo various assessments including safety monitoring for side effects, measurement of drug concentrations and immune responses, imaging scans to evaluate disease status, and quality-of-life questionnaires. The primary outcomes include tracking dose-limiting toxicities up to 35 days and treatment-emergent adverse events up to 2 years. Longer-term outcomes such as progression-free survival and overall survival will be followed for up to 5 years, with ongoing evaluations to understand the treatments impact over time.

Researchers are studying an experimental drug called odronextamab for adults with previously untreated follicular lymphoma, a type of non-Hodgkin lymphoma. The trial is a Phase 3, open-label, randomized study comparing odronextamab to rituximab combined with different chemotherapy regimens, which represent the current standard treatment. The study aims to evaluate the safety, tolerability, and how well odronextamab works compared to standard care, including side effects, drug levels in the blood, antibody development against the drug, and quality of life impacts. The study has two parts Part 1 is a non-randomized safety run-in where all participants receive odronextamab alone to assess safety and tolerability. In Part 2, participants are randomly assigned to one of two groups one receiving odronextamab followed by maintenance therapy with odronextamab, and the other receiving rituximab combined with chemotherapy followed by rituximab maintenance. Chemotherapy regimens include CHOP, CVP, or bendamustine, administered as per protocol. Participants will be monitored regularly for treatment side effects, drug concentrations, and immune responses for up to 5 years. Researchers will assess responses using imaging and other tests at multiple time points, including complete response at 30 months and progression-free survival up to 5 years. Quality of life and physical function will also be evaluated using standardized questionnaires. Safety and adverse events will be tracked for up to 2 years, ensuring comprehensive follow-up throughout the study duration.

Researchers are evaluating the efficacy and safety of combining gedatolisib and palbociclib with endocrine therapy compared to endocrine therapy and ribociclib in adults with hormone receptor-positive, HER2-negative advanced breast cancer. This Phase 3, open-label, randomized clinical trial involves patients with locally advanced or metastatic breast cancer who have either endocrine-resistant or endocrine-sensitive disease. The study aims to explore treatment options for this specific breast cancer subtype to improve outcomes for patients. Participants are assigned to one of two studies based on their endocrine sensitivity status. Study 1 includes patients with endocrine-resistant cancer who will receive either intravenous gedatolisib combined with oral palbociclib and intramuscular fulvestrant or oral ribociclib with fulvestrant. Study 2 includes endocrine-sensitive patients who will receive intravenous gedatolisib with oral palbociclib and letrozole or oral ribociclib with letrozole. Treatments are administered in cycles with specific dosing schedules, including weekly intravenous infusions and oral medications over 28-day cycles. During the trial, participants will undergo screening to confirm eligibility before randomization. Researchers will monitor progression-free survival for up to 48 months as the primary outcome, along with secondary outcomes such as overall survival, response rates, duration and time to response, clinical benefit, quality of life, and adverse events. Safety follow-up will occur 30 days after treatment, and ongoing assessments will include imaging, tumor biopsies, laboratory tests, and quality of life questionnaires. The study is expected to last several years with continuous monitoring of patient health and treatment effects.

This research is investigating the safety and effectiveness of combining Trastuzumab deruxtecan T-DXd with rilvegostomig, compared to T-DXd alone or the standard chemotherapy regimen of gemcitabine plus cisplatin with durvalumab in patients who have advanced HER2-expressing biliary tract cancer and have not received prior treatment. The study focuses on patients with unresectable, locally advanced, or metastatic biliary tract adenocarcinoma that expresses HER2 protein. Participants are randomly assigned to one of three groups one receiving T-DXd combined with rilvegostomig, another receiving T-DXd alone, and a third group receiving standard chemotherapy with gemcitabine and cisplatin plus durvalumab. All therapies are given by intravenous infusion. The study includes an initial safety run-in phase where participants complete at least one 21-day treatment cycle, followed by a randomized portion that will assess overall survival and other efficacy measures over an estimated period of up to 50 months. During the study, participants will undergo assessments including tumor tissue testing to confirm HER2 expression, evaluations of tumor lesions using RECIST criteria, and monitoring of physical function and adverse effects. Blood samples will be collected to analyze drug levels and immune responses. Researchers will track overall survival, progression-free survival, response rates, and patient-reported tolerability throughout the treatment and up to the studys end. The study duration extends until the final data collection, which may be up to several years after enrollment.

Researchers are evaluating the efficacy and safety of givinostat compared to hydroxyurea in patients with high-risk polycythemia vera PV who have the JAK2V617F mutation. PV is a chronic blood disorder that increases the risk of blood clots, progression to myelofibrosis, and transformation into acute leukemia. Patients aged 60 or older or those with a prior thrombotic event are considered high risk. Current treatments with hydroxyurea often do not fully control symptoms or long-term risks. Participants will be randomly assigned to receive either oral givinostat at 50 mg twice daily or hydroxyurea at 500 mg twice daily for 48 weeks. Dosages may be adjusted based on side effects or lack of effectiveness. After this core treatment phase, eligible patients can enter an extended treatment phase to receive long-term givinostat, allowing collection of additional safety and efficacy data. Throughout the study, participants will have regular visits to monitor blood counts, spleen size, and treatment responses. Researchers will assess the proportion of patients achieving a response at week 48, including complete hematological response and spleen size normalization. Safety and tolerability will be evaluated up to week 48. The study aims to collect comprehensive data on treatment effects and patient outcomes over time.

Researchers are evaluating the safety and therapeutic benefit of subcutaneous Surovatamig as a consolidation therapy for patients with Chronic Lymphocytic Leukemia CLL or Small Lymphocytic Lymphoma SLL who have an unmutated Immunoglobulin Heavy Chain Variable IGHV gene. This Phase III, randomized, open-label study aims to compare Surovatamig treatment versus observation after initial standard therapy in these patients. The study includes a dose optimization and safety run-in phase followed by the main Phase III treatment and observation phase. The study begins with a dose optimization and safety run-in part where two different doses of Surovatamig are tested subcutaneously to determine the recommended dose for Phase III. In Phase III, participants are randomly assigned to one of two groups one receiving the recommended dose of Surovatamig as consolidation therapy for six 28-day cycles, and the other undergoing observation for 24 weeks without additional treatment. The drug is delivered by subcutaneous injections. Participants will be closely monitored throughout the study for adverse events, disease progression, and response to treatment. Assessments include safety evaluations, measuring progression-free survival, overall survival, and various pharmacokinetic and immunogenicity parameters over up to five years. The study involves regular visits for treatment administration or observation and long-term follow-up to evaluate outcomes and safety.