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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.

Researchers are evaluating the long-term safety and effects of nerandomilast in people with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF) who have previously completed treatment with nerandomilast in earlier studies. The study aims to understand how well participants tolerate nerandomilast over time, and whether it helps improve lung function, delays symptom worsening, reduces hospital visits, or impacts survival. This is a Phase 3 open-label extension trial. Participants take nerandomilast tablets daily for up to 1 year and 10 months while continuing their usual pulmonary fibrosis treatments. The study follows an open-label design where all participants receive nerandomilast. There are no placebo or comparator groups in this extension phase. Throughout the study, participants regularly visit their doctors for health assessments and lung function tests. Doctors monitor any health problems or side effects experienced during treatment. The main outcome measured is whether participants experience any adverse events up to the final follow-up visit, which occurs at week 99. This close monitoring helps evaluate the long-term safety and potential benefits of nerandomilast in this patient group.

Researchers are evaluating the safety and effectiveness of combining durvalumab and domvanalimab compared to durvalumab plus placebo in adults with locally advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) whose disease has not worsened after definitive platinum-based concurrent chemoradiation therapy. This Phase III, randomized, double-blind, placebo-controlled, international study involves multiple centers. Participants receive intravenous infusions of durvalumab and domvanalimab or durvalumab and placebo. The treatments are given after patients have completed concurrent platinum-based chemotherapy and radiation therapy with a total radiation dose of approximately 60 Gy. The study monitors patients over time to assess treatment effects and safety. During the study, participants undergo evaluations including tumor tissue analysis for PD-L1 status, performance status assessments, and monitoring of organ and marrow function. The main outcome measured is progression-free survival up to 8 years after randomization. Researchers also monitor for any adverse effects and disease progression throughout the study period.

Researchers are evaluating the long-term safety and tolerability of dazodalibep in adults with Sjögren's Syndrome. This phase 3 open-label extension study focuses on participants who have previously received dazodalibep or placebo in earlier phase 3 trials and completed those studies through Week 48. Participants will receive dazodalibep intravenously during this long-term extension study. The first dose is administered around Week 48 (+28 days) following the prior phase 3 studies. The study monitors safety and tolerability over an extended period to assess treatment-emergent adverse events up to 152 weeks. During the study, participants will undergo regular evaluations to monitor their health and any side effects. Researchers will collect data on adverse events that emerge during treatment. The overall goal is to gather long-term safety information to better understand how participants tolerate dazodalibep when used over an extended time frame.

Researchers are investigating treatments for patients with hormone receptor-positive (HR-positive), HER2-negative early-stage breast cancer who are at higher risk of relapse after surgery within the last five years. This phase II, open-label study uses a biomarker-driven approach to monitor minimal residual disease (MRD) by analyzing circulating tumor DNA (ctDNA) in blood samples. The study includes a pre-screening phase, a molecular follow-up phase with ctDNA surveillance, and an interventional treatment phase, aiming to identify patients at molecular relapse and evaluate whether early treatment can improve outcomes. Participants first enter a ctDNA surveillance phase where tumor tissue and blood samples are collected to create individualized mutation panels. Blood is tested every three months during the first year and every six months thereafter. If ctDNA is detected, patients may enter one of four treatment arms: standard treatment followed by change, giredestrant alone, giredestrant combined with abemaciclib, or giredestrant combined with inavolisib. LHRH agonists are given as appropriate for men and premenopausal women. Treatment dosing and schedules are defined, including special dosing for certain kidney function levels. The study allows arm expansions based on ctDNA response criteria. Throughout the study, patients undergo regular ctDNA assessments to monitor treatment response. Safety and disease progression are tracked with scans and clinical evaluations. After treatment, a follow-up period collects survival and new therapy information every three months until study end. The primary outcome is measuring a decrease or clearance of baseline ctDNA three months after starting treatment. Total enrollment includes 976 patients for surveillance, with 40 allocated to treatment arms initially, and potential expansion based on results.

The target population for inclusion in this study is breast cancer patients recently diagnosed (from January 2016) with unresectable locally advanced or metastatic disease (either after a recurrence or as first diagnosis). No treatment regimen will be protocol specified. This is an observational study in which clinical decisions concerning the optimum management strategy for a particular patient are taken independently of and/or prior to, any decision by the physician to invite a patient to participate in the study. The treating physician will make all treatment decisions according to his/her regular clinical practice independent of this study. Patients enrolled on the study are free to withdraw their informed consent for the use and disclosure of health information at any time and when asked, patients are not obliged to provide a reason. Patients may request discontinuation from the study at any time. The date and the reason for withdrawal or discontinuation from the study must be recorded in the electronic case report form (eCRF). An attempt will be made to determine the date of discontinuation and final status (i. e. withdrawal of consent, loss to follow-up, death) of any patient who discontinues from the study. However, the treating clinician is encouraged to follow the patient as long as possible, until patient death or through study end. The Sponsor has the right to terminate the study at any time. The Sponsor will notify the investigator if the study is placed on hold or if the Sponsor decides to discontinue the study.

Researchers are studying the real-world effectiveness of pegcetacoplan in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). This long-term, multicenter observational study aims to fill knowledge gaps about how pegcetacoplan works in routine medical practice. It also seeks to provide important information on red blood cell transfusions and healthcare resource use before and after starting pegcetacoplan treatment. Patients who have started pegcetacoplan treatment within the last 12 months or are prescribed it at enrollment will be followed for approximately 36 months. The study will collect both retrospective data from up to 12 months before treatment start and prospective data during treatment, with a total data collection period of up to about 48 months. After stopping pegcetacoplan, patients will remain in the study for 8 weeks to monitor for any adverse events. Participants will attend their usual medical visits, and data from these visits will be collected, including effectiveness measures, safety reports, patient- and clinician-reported outcomes, and healthcare use. The primary outcome includes changes in hemoglobin levels over 6 months from the start of pegcetacoplan treatment. The study plans to enroll about 200 patients across multiple countries, and data collection includes both retrospective and prospective periods, capturing comprehensive information on pegcetacoplan use in real-world settings.

Researchers are evaluating the effectiveness and safety of combining inavolisib with a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) and letrozole compared to placebo plus CDK4/6i and letrozole. This study focuses on participants with endocrine-sensitive PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. It aims to assess treatment outcomes in the first-line setting for this specific breast cancer type. Participants will be assigned to receive either oral inavolisib once daily or a matching oral placebo once daily. All participants will also receive a CDK4/6 inhibitor on either Days 1-21 or Days 1-28 of each 28-day cycle, along with daily oral letrozole. This randomized, double-blind study will compare these two treatment combinations to monitor differences in disease progression and safety. Throughout the study, researchers will evaluate progression-free survival from the time of randomization until disease progression or death, up to 7 years. Participants will undergo assessments including tumor measurements by RECIST criteria, performance status evaluations, and monitoring of blood and organ function before treatment begins. Safety and efficacy will be closely observed during treatment, aiming to provide detailed long-term data on the study therapies.

Researchers are studying an experimental combination of two drugs called pozelimab and cemdisiran for adults with paroxysmal nocturnal hemoglobinuria (PNH), a rare blood disorder. The study aims to evaluate the long-term safety and effectiveness of this drug combination. It also investigates how the drugs behave in the body, possible side effects, and whether the body might develop antibodies against them that could affect treatment. Participants in this Phase 3 open-label extension study receive pozelimab and cemdisiran according to the study protocol. The study includes people who completed a parent study or those with a specific genetic variation (C5 polymorphism) making them resistant to certain other treatments. Treatments are administered as directed, and meningococcal vaccinations are required as part of the protocol. During the study, participants will attend clinic visits for various assessments, including safety monitoring for serious and special side effects up to week 108, and blood tests to measure changes in lactate dehydrogenase (LDH) levels up to week 36. Researchers will track adverse events, treatment tolerance, and collect data on drug levels and antibody formation. The total study duration covers long-term follow-up to better understand the treatment's effects and safety.

Researchers are evaluating a Phase 2 study called PUMA-ALI-1201 to find the optimal dose of alisertib combined with endocrine therapy for adults with hormone receptor-positive, HER2-negative metastatic or recurrent breast cancer. Participants have experienced disease progression after at least two prior endocrine therapy treatments. The study also aims to assess the safety, effectiveness, pharmacokinetics of alisertib combined with endocrine therapy, and to identify biomarker-defined subgroups that may benefit most from this combination treatment. Participants will receive alisertib tablets orally twice daily on days 1-3, 8-10, and 15-17 of each 28-day cycle. They will also receive investigator-selected endocrine therapy according to approved dosing schedules, which may include daily oral tablets of anastrozole, letrozole, exemestane, tamoxifen, or intramuscular injections of fulvestrant on specified days. The combination treatment will be administered in repeated 28-day cycles. Throughout the study, researchers will monitor responses to treatment by measuring outcomes such as objective response rate, duration of response, disease control rate, progression-free survival, and overall survival for up to 48 months. Safety will be tracked by recording treatment-emergent adverse events from first dose through 28 days after the last dose. The study includes regular assessments to evaluate treatment effects, side effects, and participant well-being over the course of the trial.