Preston

Researchers are evaluating the safety, tolerability, and therapeutic effects of a combination treatment using BNT113 and pembrolizumab compared to pembrolizumab alone for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that is positive for human papillomavirus 16 (HPV16+) and expresses the PD-L1 protein with a combined positive score of 1 or higher. This Phase II/III trial includes patients whose cancer cannot be treated with local therapies and who have not received prior systemic anticancer therapy for their current disease condition. The trial consists of two parts. Part A is a non-randomized Safety Run-In Phase to confirm the safety and tolerability of BNT113 combined with pembrolizumab at the selected dose. Part B is a randomized phase that compares BNT113 plus pembrolizumab against pembrolizumab alone as first-line treatment. Patients in Part A continue their treatment without randomization. Treatments are given by intravenous injection or infusion, and patients may receive either combination therapy or monotherapy for up to 24 months. There is also an optional pre-screening phase to test tumor samples for HPV16 DNA and PD-L1 expression before entering the main trial. Participants undergo regular assessments including tumor measurements based on RECIST 1.1 criteria confirmed by independent review. Researchers monitor treatment-emergent adverse events for up to 27 months in Part A and evaluate overall survival and progression-free survival for up to 48 months in Part B. Tumor tissue samples are collected before treatment to confirm eligibility. The study involves ongoing safety monitoring and efficacy evaluations throughout the treatment and follow-up periods.

Researchers are evaluating the safety and effectiveness of trontinemab in people aged 50 to 90 with early symptoms of Alzheimer's disease, ranging from mild cognitive impairment to mild dementia. This Phase III clinical trial focuses on those who show evidence of Alzheimer's pathology and have a recent history of cognitive decline. The study aims to measure changes in cognitive function over 72 weeks. Participants will be randomly assigned to receive either intravenous trontinemab or a placebo. The trial is designed as a double-blind, placebo-controlled study, meaning neither participants nor researchers know who receives the active drug or placebo. The treatment period lasts up to 72 weeks, during which participants will undergo various assessments to monitor their cognitive status and safety. During the study, participants will complete clinical tests including cognitive assessments and imaging such as MRI, PET scans, or cerebrospinal fluid analysis to confirm Alzheimer's pathology. A study partner will assist participants as needed. Researchers will track changes from the start of the study through week 72 using tools like the Clinical Dementia Rating. Safety monitoring and adherence to study procedures will also be closely observed throughout the trial.

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab, both in combination with platinum-based doublet chemotherapy, as a first-line (1L) treatment for patients with squamous metastatic non-small cell lung cancer (mNSCLC) whose tumors express PD-L1 (tumor cells (TC) ≥ 1%).

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 evaluating the safety and effectiveness of KarXT combined with KarX-EC in adults aged 55 to 90 who have agitation related to Alzheimer's Disease. This phase 3 study aims to better understand how these treatments impact agitation symptoms in this population by comparing them to a placebo group. Participants must have a confirmed Alzheimer's diagnosis and meet specific criteria for agitation severity to join the study. Participants will receive either the Xanomeline/Trospium Chloride Capsule, Xanomeline Enteric Capsule, or a placebo, each given at specified doses on designated days. The study is randomized, double-blind, and placebo-controlled to ensure reliable comparison of treatment effects. The treatment period lasts through Week 14, during which dosing schedules are closely followed. Throughout the study, participants will be regularly assessed using the Cohen-Mansfield Agitation Inventory-International Psychogeriatric Association (CMAI-IPA) to measure changes in agitation levels from baseline to Week 14. Caregivers will provide reports on participant status and help ensure medication compliance. Safety and symptom changes will be carefully monitored to evaluate the treatments' effects during this period.

Researchers are conducting a Phase I/II clinical trial to evaluate the safety, pharmacokinetics, and clinical activity of NUC-7738, a nucleotide analogue, in patients with advanced solid tumors and lymphoma. The study aims to determine the maximum tolerated dose (MTD) and dosing schedules of NUC-7738 alone and in combination with pembrolizumab. The trial includes patients with various cancers such as cutaneous melanoma and lymphoma, with particular focus on those who have progressed on prior therapies or have limited treatment options. In Phase I, NUC-7738 is administered intravenously as a monotherapy on either a weekly or fortnightly schedule in a dose-escalation design to assess safety and tolerability. Phase II involves dose-confirmation expansion cohorts where approximately 40 additional patients receive the selected dose and schedule of NUC-7738. Specific cohorts include patients with cutaneous melanoma receiving NUC-7738 alone or combined with pembrolizumab, and patients with lymphoma receiving NUC-7738 monotherapy. The combination cohort may expand based on efficacy signals. Participants undergo regular assessments including monitoring for dose-limiting toxicities, treatment-emergent adverse events, laboratory changes, physical exams, vital signs, and electrocardiograms from consent until 30 days after the last dose. Tumor response is evaluated every 8 weeks up to 22 months, measuring changes in tumor size, objective response rate, duration of response, disease control rate, duration of stable disease, and progression-free survival. The study may last up to approximately one year for Phase I and include long-term follow-up for tumor assessments in Phase II.

This research aims to evaluate the effectiveness and safety of two different dose schedules of pegozafermin compared to a placebo in adults with metabolic dysfunction-associated steatohepatitis (MASH) who have liver fibrosis at stage F2 or F3. This phase 3 study focuses on improving liver fibrosis and steatohepatitis in this patient group, which involves chronic liver disease associated with metabolic dysfunction. Participants will receive either pegozafermin or a placebo through subcutaneous injections. The study compares two doses of pegozafermin to assess their impact on liver fibrosis and steatohepatitis. The treatment period lasts up to 52 weeks, with outcomes measured at this time point. During the study, participants will be monitored for improvements in liver fibrosis and resolution of steatohepatitis without worsening fibrosis by week 52. Researchers will also track the time until any disease progression occurs, up to 5 years. Throughout the trial, safety and efficacy will be carefully assessed through clinical evaluations and laboratory tests to ensure participant well-being.

Researchers are evaluating the effectiveness and safety of brenipatide compared to a placebo in adults with Alcohol Use Disorder (AUD) and hazardous alcohol use. This Phase 3, multicenter, randomized, double-blind study aims to understand if brenipatide can help participants reduce or stop drinking. The study lasts approximately 56 weeks and focuses on changes in drinking patterns using the Timeline Followback Method (TLFB). Participants will receive either brenipatide (LY3537031) or a placebo, both administered by subcutaneous injection. Participants who cannot self-inject will have assistance from a trained support person. They are expected to store and use the blinded study drug as directed, maintain electronic and paper diaries, and complete questionnaires throughout the study. During the study, participants will have scheduled visits to monitor their progress, including assessments of drinking behavior and safety evaluations. Researchers will measure changes in alcohol use patterns up to 56 weeks. Participants must be motivated to reduce or stop drinking and be available for all study visits and procedures. Safety and adherence will be closely monitored throughout the trial.

Researchers are evaluating how well elacestrant works compared to standard endocrine therapy in adults with node-positive, Estrogen Receptor-positive (ER+), Human Epidermal Growth Factor-2 negative (HER2-) early breast cancer who are at high risk of the cancer returning. This is a Phase 3 global, multicenter, randomized, open-label study focusing on participants who have had early invasive breast cancer removed and meet specific receptor and risk criteria. The study aims to understand which treatment better prevents invasive breast cancer over up to five years. Participants will receive either elacestrant or one of several standard endocrine therapies, including anastrozole, letrozole, exemestane, or tamoxifen, all given as oral tablets. Treatments will be administered according to the study plan, with careful monitoring throughout the trial. The study includes adults who have already received between 24 and 60 months of prior endocrine therapy, with or without certain inhibitors, and who have completed or stopped these treatments as required. During the study, participants will be monitored for invasive breast cancer-free survival for up to five years. Researchers will perform regular assessments to track treatment effects, side effects, and cancer recurrence. The study also includes safety monitoring and may involve additional tests or evaluations as needed to ensure participant well-being throughout the trial.

Researchers are evaluating the effectiveness of Saruparib (AZD5305) compared to placebo when added to a standard radiation therapy (RT) and androgen deprivation therapy (ADT) regimen in men with high-risk and very high-risk localized or locally advanced prostate cancer who have a BRCA gene mutation. This phase III study aims to assess whether Saruparib can improve metastasis-free survival in this population. About 700 adult male participants will be randomly assigned to receive either Saruparib or placebo along with ADT. There are two groups: Cohort A includes 400 participants with newly diagnosed high-risk or very high-risk prostate cancer treated with primary RT or with high-risk biochemical recurrence after radical prostatectomy receiving salvage RT. Cohort B includes 300 participants with very high-risk locally advanced prostate cancer receiving primary RT combined with ADT and abiraterone. Saruparib and placebo will be given orally, and standard ADT and abiraterone with prednisone/prednisolone will be administered as per the regimen. Participants will be followed for up to about 93 months to monitor metastasis-free survival and overall safety. Assessments include imaging scans like CT, MRI, bone scans, and PSMA-PET to confirm disease status. The study also monitors organ function, performance status, and treatment adherence. An independent committee will review safety and efficacy data throughout the trial to ensure participant well-being and study integrity.