Manati

Researchers are evaluating the safety and tolerability of NKX019, an investigational allogeneic CD19-directed CAR natural killer (CAR NK) cell therapy, in adults with active lupus nephritis or primary membranous nephropathy. This Phase 1/2 open-label, multi-center, non-randomized study also explores preliminary efficacy, pharmacokinetics, and pharmacodynamics of NKX019 in people with these autoimmune diseases. Participants have conditions that have persisted despite standard treatments and meet specific disease activity and biopsy criteria. Participants undergo a dose escalation phase using a 3+3 design to identify recommended doses. Each treatment cycle includes lymphodepletion with fludarabine and cyclophosphamide (Flu/Cy), though some may receive cyclophosphamide alone if cytopenic, followed by three doses of NKX019. The study monitors safety during and after treatment, and additional participants may be enrolled across indications once doses are established. During the study, participants receive medical evaluations including safety assessments for treatment-emergent adverse events and dose-limiting toxicities. Researchers assess disease activity, laboratory markers, and immunologic responses. Monitoring continues from the first NKX019 dose until 30 days after the last treatment. The study spans adults aged 18 to 70 years with specific autoimmune kidney diseases meeting detailed inclusion and exclusion criteria to ensure safety and appropriate participation.

Researchers are evaluating the safety and tolerability of NKX019, an investigational allogeneic CD19-directed CAR natural killer (CAR NK) cell therapy, in participants with autoimmune diseases such as systemic sclerosis, idiopathic inflammatory myopathies, and antineutrophil cytoplasmic antibody-associated vasculitis. This Phase 1/2, open-label, multi-center, non-randomized study uses a dose escalation and dose expansion design to assess preliminary efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of NKX019 in these immune-mediated conditions. The study uses a "3+3" dose escalation design to determine recommended doses for further study. Participants receive a cycle that starts with lymphodepletion using fludarabine and cyclophosphamide (Flu/Cy), or cyclophosphamide alone if they are cytopenic, followed by three doses of NKX019. The trial includes multiple cohorts to enroll additional participants across different autoimmune disease indications and monitors treatment effects and safety throughout. Participants undergo screening and receive treatments under close observation. Researchers monitor safety outcomes including dose-limiting toxicities during the first 28 days after the initial NKX019 dose and treatment-emergent adverse events from the first dose until 30 days after the last treatment. The study collects data on clinical responses, laboratory tests, and immune effects throughout the treatment and follow-up periods, with participant involvement spanning screening, treatment, and safety monitoring phases.

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.

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 a new medicine called PF-08634404 combined with chemotherapy for people aged 18 and older who have locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma. The study includes participants who have not received prior treatment for advanced or metastatic disease and are in good health based on medical tests. This research is designed as a Phase 2/3 trial to learn about safety, response, and compare this new treatment to an approved therapy called nivolumab plus chemotherapy. The study has two parts: the first part assesses the safety and response to PF-08634404 with chemotherapy, and the second part compares this combination to nivolumab with chemotherapy. Treatments are given intravenously in repeated cycles. Participants receive either PF-08634404 plus chemotherapy or nivolumab plus chemotherapy based on the study phase and group assignment. During the study, participants undergo regular evaluations including medical tests to monitor organ function and safety. Researchers will measure treatment response using RECIST 1.1 criteria, track adverse events, and assess progression-free survival and overall survival over approximately four years. Follow-up continues through 90 days after the last treatment to monitor side effects and overall health.

Researchers are evaluating the effects of cannabis and cannabinoid use on cancer-related symptoms in adults newly diagnosed with breast, colorectal, melanoma, non-Hodgkin lymphoma, or non-small cell lung cancer. This study focuses on patients who are planning to receive or have recently started systemic cancer treatments such as chemotherapy and immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, or CTLA-4. The goal is to understand how cannabis use may be associated with symptom changes over time. Participants are enrolled in a non-interventional study where no experimental treatment is given. They complete surveys about their symptoms and cannabis use, and their medical records are reviewed regularly. The study tracks cancer-related symptoms monthly for up to 12 months after enrollment, allowing researchers to observe symptom patterns during ongoing cancer treatment. An optional substudy is available at select sites for patients with non-small cell lung cancer receiving paclitaxel and ICIs. During the study, participants complete online surveys in English or Spanish at their convenience, either at home or in clinic. Medical records are examined to gather information on treatments and health status. The main outcome measured is cancer-related symptoms, assessed monthly for one year. Safety monitoring includes ensuring participants have an expected life expectancy of at least six months and are not enrolled in hospice. The study aims to enroll 2000 patients across multiple sites in the United States.

The goal of this trial is to determine the efficacy of advanced cognitive training for cancer survivors suffering from cancer- and cancer-treatment-related cognitive dysfunction. For millions of cancer survivors, cognitive dysfunction is a prevalent, severe, and persistent problem that has long been associated with poor work-related and health-related outcomes. Evidence suggests that a significant subset of breast cancer survivors (BCS) incur cognitive changes that may persist for years after treatment. Unfortunately, the scientific basis for managing these cognitive changes is extremely limited. Available evidence from pilot studies, including our work, suggests that advanced cognitive training, which is based on the principles of neuroplasticity (ability of brain neurons to re-organize and form new neural networks), may be a viable treatment option. However, previous trials to date have been limited by lack of attention-controlled designs, small samples of BCS, or limited outcome measures. Therefore, to overcome limitations of past studies and build on our pilot results, the purpose of this 2-group, double-blind, randomized controlled trial is to conduct a full-scale efficacy trial to compare advanced cognitive training to attention control in BCS.

Researchers are evaluating how to best recommend chemotherapy for patients with colon cancer after surgery by using the presence or absence of circulating tumor DNA (ctDNA) in the blood. This approach aims to identify microscopic residual tumor cells and may provide better risk prediction for cancer recurrence compared to traditional methods. The trial focuses on patients with Stage IIB, IIC, or III colon cancer who have undergone complete tumor removal. Participants will have their tumor tissue and blood tested centrally using the Signatera assay to determine ctDNA status. Patients without detectable ctDNA may avoid chemotherapy, while those with detectable ctDNA are considered at higher risk and will be randomly assigned to receive different chemotherapy regimens, including mFOLFOX6, CAPOX, or mFOLFIRINOX, given intravenously or orally over periods ranging from 3 to 6 months. The study includes initial screening, treatment, and possible second randomization for patients whose ctDNA status changes during monitoring. During the study, participants will undergo various assessments including blood tests, imaging scans, and performance evaluations to monitor their health and response to therapy. Researchers will track the time to ctDNA positivity and disease-free survival for up to 3 and 5 years, respectively. Safety and treatment effects will be closely observed throughout the study duration, ensuring thorough follow-up and monitoring for all participants.

Researchers are evaluating different telephone-based symptom monitoring approaches to reduce symptom burden and psychological distress, including depression and anxiety, in people undergoing oral anti-cancer treatment. The study compares interactive voice response (IVR) symptom monitoring alone to automated telephone symptom management (ATSM) combined with telephone interpersonal counseling (TIPC). Symptoms often cause treatment interruptions and unplanned healthcare use, and managing these symptoms is especially challenging in community oncology settings. The study aims to learn which methods best help patients manage symptoms and improve outcomes during cancer treatment. Participants are assigned to one of two groups. In the first group, patients receive weekly IVR symptom monitoring calls for 12 weeks, with their symptom reports sent to their healthcare providers. In the second group, patients receive a Symptom Management and Survivorship handbook along with the IVR calls. Those reporting anxiety, discouragement, or sadness for two consecutive weeks early in the study also receive up to 8 weeks of telephone counseling (TIPC) focused on psychological distress and social support. After the 12-week intervention, patients are followed up for an additional 5 weeks, while healthcare practice personnel are assessed at study start and at 12 and 25 months. During the study, patients complete weekly symptom assessments via phone calls lasting 15 to 30 minutes depending on their group. Researchers collect data on symptom severity using a toxicity index, healthcare use, and psychological symptoms over the first 12 weeks and during follow-up. The study also evaluates how feasible and acceptable the interventions are within community oncology practices and estimates the costs and potential savings related to symptom management. Patient-reported financial burden and the impact of concurrent cancer treatments are also explored.