St. Louis

Researchers are evaluating (Z)-endoxifen as a potential treatment for premenopausal women with estrogen receptor-positive (ER+) and HER2-negative breast cancer. This phase 2 open-label study includes two parts: a pharmacokinetic (PK) phase to understand how the body processes the drug and a treatment phase to assess the drug's effects on tumor growth. The study aims to see if (Z)-endoxifen can slow or stop tumor growth by measuring changes in a biomarker called Ki-67. Participants are premenopausal women who meet specific cancer and health criteria. Participants in the PK part will take (Z)-endoxifen capsules daily at varying doses (20 mg, 40 mg, or 80 mg). Some will also receive a monthly injection of goserelin, a drug that temporarily stops estrogen production in the ovaries. The treatment cohort will receive both (Z)-endoxifen and goserelin. Tumor tissue samples will be collected by breast biopsy after about 4 weeks to assess the Ki-67 biomarker. Participants showing tumor response may continue treatment for up to 24 weeks or until they undergo surgery. Throughout the study, participants will have blood draws to measure drug levels and tumor markers, breast biopsies, imaging scans, and safety assessments. The main outcomes include measuring (Z)-endoxifen levels after 4 weeks, the rate of Ki-67 reduction, and tumor response after 24 weeks. Study participation lasts up to 6 months, including treatment, surgery, and a follow-up visit one month after surgery.

Researchers are evaluating two dosage schedules of the drug 5-Fluorouracil (5-FU) as second-line treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (RM-HNSCC) who have previously been treated with platinum-based chemotherapy and PD-1 inhibitors. This phase II randomized trial aims to assess the effectiveness, safety, and side effects of these two regimens. The study tests whether each 5-FU regimen achieves an overall response rate of at least 10%, while monitoring treatment-related adverse events and changes in dosage or treatment interruptions. Participants will be randomly assigned to one of two groups: Arm 1 will receive 5-FU for two days every two weeks (2D-Q2W), considered the experimental schedule, while Arm 2 will receive 5-FU for four days every three weeks (4D-Q3W), the standard schedule. Dose modifications will be made based on how well patients tolerate the drug. Treatment is expected to last up to four months. During the study, participants will be monitored for tumor response using RECIST v1.1 criteria and for side effects using CTCAE v5.0 standards. Researchers will track dose interruptions, discontinuations, and modifications. The main outcome measure is the overall response rate from the start to the end of treatment. The study includes evaluations of blood counts, organ function, and performance status to ensure participants meet safety requirements throughout the trial.

Researchers are investigating the effects of XYOSTED as a testosterone replacement therapy in adolescent males aged 12 to under 18 years who have primary or secondary hypogonadism. This Phase 3/4, open-label, multicenter study aims to evaluate how well XYOSTED supports puberty continuation or induction, as well as its dosage, safety, and testosterone level outcomes. Participants have a confirmed deficiency or absence of endogenous testosterone and will be assessed for pubertal development and hormone levels before starting treatment. Participants will receive XYOSTED injections with dosages tailored to their weight and targeted Tanner Stage of puberty. Dose adjustments will be made regularly based on serum total testosterone levels measured at specific intervals after dosing, with evaluations approximately every three months to reach desired testosterone levels. After completing the 52-week primary study, participants may join a 24-month long-term safety extension with clinic visits every six months for ongoing clinical, laboratory, and pharmacokinetic assessments. During the study, participants will undergo thorough clinical examinations including pubertal staging, multiple testosterone measurements, and monitoring for safety and pharmacokinetics throughout treatment and extension periods. Researchers will track changes in testosterone levels from enrollment through week 53 and monitor overall safety. The study includes detailed follow-up and dose management to support pubertal development and assess long-term effects of XYOSTED therapy in this population.

Researchers are studying a new formulation of 64Cu-LLP2A to evaluate its use in imaging blood cancers such as multiple myeloma and various types of low-grade lymphoma. This phase of the trial includes healthy volunteers to confirm that the new formulation provides similar dosimetry as seen in earlier studies, as well as patients diagnosed with these hematologic malignancies, including those who have had bone marrow transplants and show negative imaging but possible recurrence. The study is an early Phase 1 trial aimed at assessing this imaging agent's safety and effectiveness in these populations. Participants will receive the investigational drug 64Cu-LLP2A, produced under strict manufacturing conditions, followed by PET/CT scans to monitor how the drug distributes in the body. The imaging results are generally not shared with patients or their doctors unless unexpected findings suggest further evaluation is needed. The study involves lying still during the PET/CT scanning sessions, which last up to 75 minutes. During the study, participants will undergo PET/CT scans lasting up to two days for organ dosimetry assessment. Researchers will monitor the safety and tolerability of the new formulation by tracking any adverse events from the start of drug administration through a follow-up period of up to seven days. Participants must be able to follow study procedures, remain still during imaging, and meet other health and safety criteria to ensure accurate and safe participation.

Researchers are studying the safety and effectiveness of 67Cu-SAR-bisPSMA in men with metastatic castrate resistant prostate cancer that expresses PSMA. This Phase I/IIa trial focuses on participants whose cancer has progressed despite androgen deprivation therapy and prior treatments with androgen receptor pathway inhibitors. The study aims to understand how the drug distributes in the body, determine safe dosing levels, and evaluate treatment responses over several years. Participants receive two drugs: 64Cu-SAR-bisPSMA for imaging and dosimetry, and 67Cu-SAR-bisPSMA for treatment. The study includes a dose escalation phase to find the maximum tolerated or feasible dose of a single 67Cu-SAR-bisPSMA dose over 8 weeks, followed by a recommended dosing phase with two doses over 14 weeks. Imaging with PET/CT scans using 64Cu-SAR-bisPSMA helps model dosimetry for the therapeutic 67Cu-SAR-bisPSMA. The treatment is given under close monitoring to assess safety and response. During the study, participants undergo PET/CT scans, blood tests, ECGs, and vital sign monitoring at various times up to 5 years to track drug distribution, treatment effects on prostate specific antigen levels, radiographic cancer response, and any side effects. Safety is closely followed through laboratory results and adverse event reporting. Participants are monitored for long-term tolerability and treatment outcomes, with study involvement lasting up to five years.

This research aims to evaluate the effects of litifilimab (BIIB059), a monoclonal antibody, in adults with active subacute or chronic cutaneous lupus erythematosus (CLE), with or without systemic lupus erythematosus (SLE). Participants have active skin symptoms of CLE that have not improved with antimalarial therapy or had difficulties continuing that treatment. The study focuses on reducing skin disease activity using several scores including CLA-IGA-R and CLASI, while also assessing safety, immune response, and quality of life. Participants will be randomly assigned to receive either litifilimab or a placebo injection under the skin every four weeks during a 24-week double-blind period where neither participants nor researchers know which treatment is given. After this, all participants will receive litifilimab injections every four weeks for an additional 28 weeks. Those who complete the treatment may join a long-term extension study or enter a follow-up safety period lasting up to 24 weeks. Total participation may last up to 80 weeks. Throughout the study, researchers will monitor skin disease activity using the CLA-IGA-R erythema score and the CLASI-A activity score to see how many participants improve. They will also assess safety, tolerability, immune system effects, and participants' quality of life using questionnaires. These evaluations occur regularly during both treatment periods and follow-up to understand the impact of litifilimab on CLE symptoms and overall health.

Researchers are evaluating the safety and effectiveness of tenapanor in adults with Chronic Idiopathic Constipation (CIC) in this 26-week phase 3 study. The study is randomized, double-blind, and placebo-controlled, involving multiple centers. It aims to compare three doses of tenapanor (5 mg, 25 mg, and 50 mg taken twice daily) against a placebo, with a focus on improving spontaneous bowel movements. Participants will first undergo a 2-week screening where their eligibility is assessed through medical history, physical exams, lab tests, ECG, and self-reported constipation symptoms using an electronic diary (eDiary). Eligible patients will then be randomly assigned to receive one of the three doses of tenapanor or placebo twice daily for 26 weeks. During this treatment period, patients will continue daily and weekly symptom reporting via the eDiary and attend regular safety visits at weeks 2, 4, 8, 12, 16, 20, and 26. After completing the 26-week treatment, patients enter a 4-week treatment-free safety follow-up period to monitor any adverse events. A final visit occurs at the end of this follow-up to assess safety. The main outcome measured is the durable complete spontaneous bowel movements response over 12 weeks. Overall, the study involves careful monitoring of symptoms, safety, and treatment effects over approximately 32 weeks.

Researchers are investigating new treatments for extensive-stage small cell lung cancer (ES-SCLC), a type of lung cancer that has spread within or beyond the lungs. This trial evaluates the safety and effectiveness of combining two study medicines, gocatamig and ifinatamab deruxtecan (I-DXd), with or without standard chemotherapy and immunotherapy. Gocatamig is a T-cell engager therapy that helps the immune system target cancer cells, while I-DXd is an antibody drug conjugate designed to deliver cancer-killing agents directly to tumor cells. Participants will receive different treatment combinations based on the study part and arm to which they are assigned. Treatments include intravenous administration of gocatamig, I-DXd, atezolizumab, carboplatin, and etoposide. Rescue medications may be given as needed to manage side effects such as cytokine release syndrome or infusion reactions. Participants may be assigned to various treatment groups either per investigator choice or randomized, with some receiving maintenance treatments after initial induction therapy. Throughout the study, participants will be monitored for safety, including the occurrence of adverse events and dose-limiting toxicities, for up to about 58 months. Researchers will also assess tumor response by measuring cancer size changes. Other evaluations include biopsies, imaging scans, and clinical assessments to determine how well participants tolerate the treatments and how their cancer responds. The total duration of participation and follow-up will vary depending on the study phase and treatment arm.

Researchers are evaluating a new vaccine called V118C designed to prevent pneumococcal disease, which includes infections caused by the Streptococcus pneumoniae bacteria. This study focuses on toddlers and infants to understand the safety and tolerance of V118C. It is a Phase 1 trial that compares V118C to an existing pneumococcal vaccine called PCV20 in children. The study has two parts: Stage 1 involves toddlers aged 12 to 15 months who have already received three doses of PCV20 during infancy. Stage 2 involves infants around 2 months old who will receive four doses of V118C using a 3+1 schedule (three infant doses plus one toddler dose). Both vaccines are given by intramuscular injection. The study compares safety and immune response between V118C and PCV20. Participants will be monitored for immediate reactions within 30 minutes after vaccination and for local and systemic side effects up to 7 days post-vaccination. Unsolicited adverse events will be tracked up to 28 days, and serious or medically attended events will be assessed for up to 12 months after vaccination. The study aims to collect detailed safety and tolerability information over this period.

Researchers are investigating new treatments for people with high-risk, early-stage breast cancer, specifically targeting triple-negative breast cancer (TNBC) and hormone receptor (HR)-low positive/HER2-negative breast cancer. These types have little or no HER2 protein and involve hormones like estrogen or progesterone. The study aims to evaluate if the addition of sacituzumab tirumotecan (sac-TMT), a targeted therapy, combined with pembrolizumab and chemotherapy can improve outcomes compared to pembrolizumab with chemotherapy alone. Participants receive treatments including sacituzumab tirumotecan, pembrolizumab, and chemotherapy drugs such as carboplatin and paclitaxel, all given by intravenous infusion. Rescue medications like antihistamines, acetaminophen, dexamethasone, or steroid mouthwash may be used as needed. The study is randomized and open-label, comparing sac-TMT followed by chemotherapy plus pembrolizumab to chemotherapy and pembrolizumab without sac-TMT. During the study, researchers will monitor participants up to about 30 weeks to assess the percentage of people with no remaining cancer cells at surgery. They will also follow participants for up to approximately 92 months to track event-free survival, meaning time without cancer growth, spread, or return. Participants will undergo imaging, clinical assessments, and laboratory tests to evaluate treatment effects and safety throughout the study.