Lincoln

Researchers are evaluating the use of PET imaging with the radioligand 18FPI-2620 to detect tau protein deposits in people with Alzheimers disease and healthy controls. This open-label, multi-center, non-randomized Phase 3 study aims to compare PET imaging results during life with brain tissue analysis after death to better understand tau pathology in Alzheimers. The study is sponsored by Lantheus Biosciences Ltd. and focuses on diagnostic accuracy and safety of this imaging technique. Participants receive an intravenous injection of 18FPI-2620 at a dose of 185 MBq 20. The study involves a PET scan procedure that participants must tolerate, including lying still in the scanner. There are no randomized groups or placebo controls as this is an open-label study. The research compares the PET imaging findings with post-mortem brain autopsy results to evaluate the ability of this imaging to detect tau deposits accurately. During the study, participants undergo PET imaging and are monitored for their ability to tolerate the scan. Brain donation consent is required for post-mortem histopathological comparison. Researchers assess the diagnostic performance of the PET scan in correctly identifying tau-related pathology and Alzheimers disease changes. The primary outcome focuses on the accuracy of visual assessment of PET images compared to autopsy findings, with follow-up continuing until study completion and an average of one year after death.

Researchers are evaluating new treatment options for people with high-risk non-muscle invasive bladder cancer HR NMIBC, a type of bladder cancer that affects the inner lining of the bladder but has not spread to the muscle or beyond. This includes carcinoma in situ CIS, a flat form of bladder cancer limited to the bladders surface. The study aims to find out if adding intismeran autogene, an immune system-targeting treatment, to the standard Bacillus Calmette-Guerin BCG therapy can improve outcomes for people with HR NMIBC by helping the immune system attack the cancer more effectively. Participants are assigned to different groups. One group receives both intismeran autogene by intramuscular injection every three weeks for nine doses along with BCG treatment given once weekly for six weeks, followed by additional weekly doses at later weeks. Another group receives BCG alone on the same schedule, while a third group receives only intismeran autogene. The study compares these treatments to see if the combination improves survival without cancer growth, spread, or return. During the study, participants will be monitored for up to approximately five years to track event-free survival, recurrence-free survival, overall survival, and other outcomes. Researchers will also evaluate adverse events and treatment tolerability. Follow-up includes assessments at regular intervals to observe disease status and safety. The total participation time may last several years to gather long-term data on treatment effects.

Researchers are investigating new treatments for high-risk, early-stage breast cancers that are either triple-negative or hormone receptor-low positive and HER2-negative. These types of breast cancer have limited amounts of certain proteins that affect growth, making them challenging to treat. This Phase 3 trial aims to compare the effects of adding sacituzumab tirumotecan, a targeted therapy, to pembrolizumab and chemotherapy against pembrolizumab with chemotherapy alone in controlling cancer growth and spread. Participants are randomly assigned to one of two treatment groups. One group receives sacituzumab tirumotecan intravenously every two weeks along with pembrolizumab every three weeks for 12 weeks, followed by pembrolizumab combined with carboplatin and paclitaxel for another 12 weeks. After this, surgery and optional radiation therapy occur, followed by pembrolizumab infusions for up to about 28 weeks. Additional treatments such as olaparib, capecitabine, or doxorubicin with cyclophosphamide may be given if cancer remains. The other group receives chemotherapy drugs carboplatin, paclitaxel, cyclophosphamide, and doxorubicin or epirubicin alongside pembrolizumab during similar time frames, followed by surgery, radiation, and pembrolizumab maintenance with possible additional treatments. Throughout the study, participants undergo assessments including surgery to remove tumors, imaging, and laboratory tests. Researchers measure cancer cell presence after surgery and monitor how long participants live without cancer progression or recurrence, as well as overall survival. Quality of life and side effects are tracked using questionnaires over several years. Safety is monitored by recording adverse events and treatment discontinuations. The study may last up to around 115 months for long-term follow-up.

Researchers are exploring new treatments for radiographic axial spondyloarthritis r-axSpA, a type of arthritis causing pain, stiffness, and swelling in the spine and pelvic joints. This study aims to find out if different doses of tulisokibart, a study medicine, can improve symptoms of r-axSpA better than a placebo. A placebo looks like the medicine but contains no active drug, helping researchers understand tulisokibarts effects. Participants will be randomly assigned to receive either a high, medium, or low dose of tulisokibart, or a placebo, all given by subcutaneous injection. The study includes a 16-week placebo-controlled period followed by a 124-week long-term extension, which has a 40-week main extension and an 84-week optional extension. Participants on low dose or placebo will be rerandomized at week 16 to medium or high doses of tulisokibart. During the study, participants will undergo regular assessments including symptom evaluations, physical function tests, and MRI scans at the start and week 16. Researchers will track response rates, changes in disease activity, pain levels, and quality of life measures. Safety will be monitored throughout, and the study lasts up to about 140 weeks. The main outcome is the percentage of participants achieving a significant improvement in symptoms at week 16.

Researchers are investigating new ways to treat rheumatoid arthritis RA, especially for people whose symptoms do not respond well to standard treatments like methotrexate MTX. This study aims to evaluate a medicine called tulisokibart to see if it can reduce active RA symptoms better than a placebo. The study focuses on different doses of tulisokibart to determine which dose might be most effective while participants continue their MTX treatment. Participants will be randomly assigned to receive one of several treatments MTX plus a high, medium, or low dose of tulisokibart, or MTX plus a placebo that looks like tulisokibart but contains no active medicine. Those on the low dose or placebo will be re-randomized at week 12 to either a medium or high dose of tulisokibart. The study includes a 12-week placebo-controlled period followed by a long-term extension lasting 116 weeks, split into a 44-week main extension and a 72-week optional extension. During the study, participants will have their RA symptoms and response to treatment assessed using criteria such as the American College of Rheumatology 20 response at week 12. Researchers will also monitor safety by recording adverse events and treatment discontinuations up to about week 142. The study involves regular evaluations, including questionnaires and clinical assessments, to track disease activity, physical function, and overall health over the entire study period.

Researchers are evaluating treatments for germinal center B-cell-like diffuse large B-cell lymphoma GCB DLBCL, a fast-growing blood cancer affecting immature B-cells. This phase 2 study compares the effects of zilovertamab vedotin combined with R-CHP chemotherapy versus polatuzumab vedotin combined with R-CHP in people newly diagnosed with this type of lymphoma. The goal is to see if the cancer responds better to one treatment over the other. Participants will be randomly assigned to receive either zilovertamab vedotin or polatuzumab vedotin, both given by intravenous infusion on the first day of each 3-week cycle for up to six cycles about 4 months. Alongside these drugs, participants will receive cyclophosphamide, doxorubicin, and rituximab or a rituximab biosimilar by IV infusion, plus prednisone or prednisolone orally for five days each cycle. Those with high-risk DLBCL may receive two additional cycles of rituximab or its biosimilar. During the study, participants will have scans and tests to measure cancer response using established criteria over up to 31 months. Researchers will also monitor survival rates, quality of life, and side effects for up to several years. Safety assessments and treatment adherence will be tracked throughout the study and follow-up periods, ensuring thorough evaluation of each treatments impact.

Researchers are investigating new treatments for people with high-risk, localized non-small cell lung cancer NSCLC that has been completely removed by surgery. This study aims to learn if one or two investigational treatments can help prevent the cancer from returning. The main goal is to see if adjuvant intismeran autogene V940, given alone or combined with subcutaneous pembrolizumab and berahyaluronidase alfa, improves disease-free survival compared to placebo in patients with completely resected high-risk Stage I NSCLC. Participants will be randomly assigned to one of three groups one group receives intismeran via intramuscular injection plus pembrolizumab coformulated with berahyaluronidase alfa via subcutaneous injection another group receives only intismeran via intramuscular injection and the third group receives a placebo injection matching the intismeran dose. The study treatments are given to evaluate their effects on preventing cancer recurrence after surgery. During the study, participants will be monitored for disease-free survival through blinded independent central review for up to approximately 98 months. Additional measures include distant metastasis-free survival, overall survival, and quality of life assessments. Researchers will also track adverse events and study treatment discontinuations for up to about 144 months. Participants will provide tissue and blood samples and undergo regular assessments to evaluate safety and treatment effects throughout the study period.

Researchers are investigating new treatment options for people with locally advanced non-small cell lung cancer NSCLC that cannot be surgically removed and has a specific gene mutation called KRAS G12C. The study aims to find out if combining the drug calderasib MK-1084 with durvalumab, an immunotherapy, can help patients live longer without their cancer growing or spreading after they have completed chemotherapy and radiation therapy. This is a Phase 3 randomized clinical trial sponsored by Merck Sharp Dohme LLC. Participants in this study will be randomly assigned to receive either calderasib plus durvalumab or a placebo plus durvalumab. Calderasib is given as a tablet taken by mouth, while durvalumab is administered through an intravenous IV infusion. The study uses a double-blind design, meaning neither participants nor researchers know who receives the active drug or placebo. Patients must have completed prior platinum-based chemoradiotherapy without disease progression to join. During the trial, participants will be closely monitored for how long they live without cancer progression, known as progression-free survival, for up to about six years. Additional outcomes include overall survival, response rates, adverse events, quality of life, and other health measures tracked for up to nine years. Researchers will collect tumor tissue samples and assess biomarkers such as PD-L1 status. Safety and treatment effects will be evaluated throughout the study, which will last several years.

Researchers are evaluating rilvegostomig compared with pembrolizumab monotherapy as a first-line treatment for people with metastatic non-small cell lung cancer mNSCLC whose tumors have high PD-L1 expression. This Phase III, global, randomized, and double-blind study aims to assess the efficacy and safety of these treatments in this patient population. The trial is sponsored by AstraZeneca and focuses on patients with specific tumor characteristics and no certain genetic mutations. Participants will receive either rilvegostomig or pembrolizumab intravenously on Day 1 of each 21-day cycle. The study has two treatment arms one for the investigational drug rilvegostomig and one for the active comparator pembrolizumab. Both treatments are given as monotherapy to understand their effects as initial therapy in this cancer setting. During the study, participants will be monitored for overall survival and progression-free survival for up to approximately 5 years. Additional assessments include tumor response, duration of response, time to second progression or death, drug pharmacokinetics, immunogenicity, and patient-reported outcomes related to physical function, quality of life, and lung cancer symptoms. The study involves regular evaluations to track treatment effects and safety over an extended period.

Researchers are evaluating the effectiveness and safety of two treatments, rilvegostomig and pembrolizumab, each combined with platinum-based doublet chemotherapy, as first-line therapy for patients with metastatic non-squamous non-small cell lung cancer mNSCLC whose tumors express PD-L1. The study is a Phase III, randomized, double-blind trial conducted globally at multiple centers. It focuses on patients with tumors expressing PD-L1 at 1 or higher and aims to compare these treatment combinations in this specific lung cancer population. Participants will be randomly assigned to one of two groups. One group receives rilvegostomig intravenously on Day 1 of each 21-day cycle, combined with platinum-based chemotherapy carboplatin or cisplatin and pemetrexed, followed by maintenance rilvegostomig plus pemetrexed monotherapy. The other group receives pembrolizumab intravenously on the same schedule with the same chemotherapy drugs, followed by pembrolizumab plus pemetrexed maintenance. Chemotherapy is given for up to four cycles. During the study, participants will be monitored for overall survival and progression-free survival for up to approximately five years. Researchers will also assess response rates, duration of response, pharmacokinetics, immunogenicity, and patient-reported physical function and quality of life. Safety will be carefully tracked throughout the study. The trial began in late 2024 and is expected to conclude around March 2030.