Belleville

Researchers are conducting a multinational, multicenter observational study to understand the real-world use of garadacimab in patients with hereditary angioedema HAE. The study includes patients who are newly starting garadacimab treatment as part of their regular clinical care. The main goal is to evaluate the effectiveness of garadacimab by comparing the rate of HAE attacks before and after treatment over a 24-month period, along with assessing safety and quality of life. Participants will receive garadacimab as prescribed by their doctors in routine practice, without any additional interventions from the study. There is one study group consisting of patients treated with garadacimab. Data collection includes information from patient medical records, electronic diaries, and routine clinical visits. Retrospective and prospective data on HAE attacks, prior treatments, safety, and healthcare resource use will be gathered throughout the study. Each participant will be followed for 48 months from the first garadacimab dose. During this time, researchers will collect data through electronic diaries, medical record reviews, and scheduled clinical assessments. Outcome measures include attack rates, adverse event monitoring, angioedema control, and quality-of-life questionnaires. This long-term follow-up helps capture the real-world experience and safety of garadacimab in routine care.

Researchers are evaluating camizestrant against standard endocrine therapy for patients with ER-positive, HER2-negative early breast cancer who have an intermediate or high risk of disease recurrence. These patients must have completed locoregional therapy and at least 2 to 5 years of standard adjuvant endocrine therapy. The study is a Phase III open-label trial focused on improving outcomes for these patients over a long-term period. Participants are randomly assigned to receive either camizestrant orally or continue with the standard endocrine therapy chosen by their investigator, which may include aromatase inhibitors exemestane, letrozole, anastrozole or tamoxifen. Treatment in each group lasts for 60 months. The study allows prior use of CDK46 inhibitors and includes a follow-up period extending up to 10 years from the last patient randomization. During the study, participants will undergo regular assessments to monitor invasive breast cancer-free survival and other outcomes such as invasive disease-free survival, distant relapse-free survival, overall survival, and safety. Researchers will also evaluate symptoms like joint pain, hot flushes, and vaginal dryness using specific scales, along with quality of life measures and pharmacokinetics. Safety monitoring continues up to 28 days after the last dose, and participants remain under observation for up to 10 years total.

Researchers are evaluating the effectiveness of remibrutinib compared to dupilumab as add-on treatments for adults with moderate to severe chronic spontaneous urticaria CSU that is not well controlled by second generation H1-antihistamines sgH1-AH. This Phase 3b, multi-center, randomized, double-blind, double-dummy study focuses on early treatment effects within 4 weeks. The study addresses the need for better management of CSU symptoms such as hives and itch. Participants will be assigned to one of two treatment groups one group will receive remibrutinib tablets twice daily plus placebo injections, while the other group will receive dupilumab injections with matching placebo tablets. Both groups continue their stable background therapy of sgH1-AH daily. The study includes a screening period up to 4 weeks, a 12-week core double-blind treatment period, and an optional 12-week open-label extension where all participants may receive remibrutinib if it is not commercially available. After treatment, safety follow-up occurs for up to 12 weeks, with phone calls and possible site visits. Participants will be monitored through regular assessments including symptom severity scores, urticaria activity scores, and daily diaries. Safety follow-up includes phone calls and visits depending on treatment continuation. The main outcome is the change in weekly urticaria activity score at Week 4. Other measures include severity of hives and itch at Weeks 1 and 4. Total study participation may last up to 24 weeks, including optional extension and follow-up phases.

Researchers are evaluating the study medicine PF-08046054 compared to the standard treatment docetaxel in adults with non-small cell lung cancer NSCLC that has PD-L1 expression of 1% or higher. These participants have cancer that has spread or cannot be treated with surgery or definitive radiation and have shown disease progression during or after previous treatments including PD-L1 or PD-1 inhibitors, platinum-based chemotherapy, and targeted therapies for known genomic alterations. The study is a randomized phase 3 trial assessing treatment options for advanced NSCLC. Participants are randomly assigned to one of two groups one receives PF-08046054 as an intravenous IV infusion twice during each 21-day cycle, and the other receives docetaxel as an IV infusion once every 21 days. The study treatment may continue for up to 5 years if the participants cancer responds to therapy. Both treatments are given in cycles, and participants receive the medicine through infusions during clinic visits. During the study, participants will have regular clinic visits to monitor their health and how well the treatment is working. Assessments include measuring overall survival, progression-free survival, tumor response rates, and quality of life through questionnaires. Safety is monitored for adverse events up to 90 days after treatment ends. Blood samples are also taken to study the medicines levels and immune response. The total study duration can be up to 5 years depending on individual responses and outcomes.

Researchers are evaluating the combination of atebimetinib with a modified schedule of gemcitabine and nab-paclitaxel compared to the standard gemcitabine and nab-paclitaxel regimen in patients with metastatic pancreatic adenocarcinoma. This Phase 3, global, randomized, open-label study aims to determine if the new combination improves overall survival when used as a first-line treatment. The study focuses on patients who have not received prior systemic anti-cancer therapy and have measurable disease. Participants will be randomly assigned to one of two groups one group will receive atebimetinib daily by mouth along with biweekly intravenous infusions of gemcitabine and nab-paclitaxel modified dosing, while the other group will receive the standard regimen of weekly intravenous infusions of gemcitabine and nab-paclitaxel for three weeks followed by one week without treatment. Treatment continues as per the study protocol to compare these approaches. Throughout the study, participants will undergo assessments including measurements of overall survival, progression-free survival, response rates, disease control, adverse events, and quality of life using a standardized questionnaire. These evaluations will be conducted for up to approximately two years. Safety and treatment effects will be closely monitored during this time, with the entire study expected to complete by early 2029.

This research aims to evaluate the safety and effectiveness of adjusting fluoropyrimidine FP chemotherapy doses based on genetic testing for DPYD variants in cancer patients. The study focuses on patients with cancers such as colorectal, breast, head and neck, and gastrointestinal neoplasms. It compares the occurrence of severe FP-related toxicities in patients with one DPYD gene variant receiving reduced doses against patients with normal DPYD genes receiving standard doses. This prospective treatment study seeks to validate DPYD-guided dosing strategies in a real-world clinical setting. Participants receive treatment in two groups the control arm receives 100% of standard FP doses according to the BEACON order plan, with dose reductions applied if severe toxicities occur. The experimental arm includes patients with one DPYD variant who start with 50% of the regular FP dose for the first two cycles, with possible dose escalation if tolerated. The chemotherapy drugs studied include Fluorouracil injection and Xeloda Capecitabine. Throughout the study, participants are monitored for severe fluoropyrimidine-related toxicities Grade 3 to 5 over a period of up to 24 months. Researchers will also track patterns of dose modifications, such as reductions or escalations. The study involves genetic testing before therapy, regular assessments of treatment response and safety, and follow-up to measure outcomes related to toxicity and treatment adjustments.

Researchers are evaluating the combination of lasofoxifene and abemaciclib compared to fulvestrant and abemaciclib for treating pre- and postmenopausal women and men with locally advanced or metastatic estrogen receptor positive ERhuman epidermal growth factor 2 negative HER2- breast cancer who have an ESR1 mutation and have previously been treated with ribociclib or palbociclib. The study aims to compare the effectiveness, safety, and tolerability of these two treatment combinations. Participants are randomly assigned to one of two groups one receives 5 mg daily oral lasofoxifene plus oral abemaciclib 150 mg twice a day the other receives fulvestrant 500 mg via intramuscular injections on Days 1, 15, and 29 and then monthly thereafter, combined with oral abemaciclib 150 mg twice a day. This open-label study assesses these treatments over approximately three years. During the trial, participants will be monitored through regular assessments including tumor measurements, survival tracking, quality of life questionnaires, and evaluation of adverse events. Researchers will measure progression-free survival as the primary outcome and also track response rates, overall survival, treatment duration, and time to chemotherapy. Brain metastases patients meeting specific criteria are allowed, and safety is closely observed throughout the study period which may last up to about three years.

Researchers are studying patients with non-small cell lung cancer NSCLC to better understand how the cancer changes on a molecular level during standard treatments. The study aims to track the diseases progress and explore how changes in circulating tumor DNA ctDNA might predict cancer recurrence and treatment outcomes. This observational study collects clinical and molecular health data over time from patients receiving usual care. The study involves two groups of patients. The first group includes patients with early-stage NSCLC Stages I to IIIB who are treated with surgery and possibly additional therapies before or after surgery. The second group includes patients with advanced stage IV NSCLC receiving first-line immunotherapy, either alone or combined with chemotherapy. Patients will provide blood samples regularly during their routine care to help researchers analyze ctDNA and its changes over time. Participants will be asked to provide tumor samples and give additional blood samples during standard surveillance visits. Researchers will monitor disease-free survival and overall survival over periods up to five years. They will also compare ctDNA testing results with traditional imaging methods used every six months to detect cancer recurrence. The study tracks various outcomes, including treatment patterns and progression-free survival, to gain a detailed understanding of how the disease evolves under standard care.

Researchers are evaluating the efficacy and safety of Adagrasib alone and in combination with pembrolizumab for patients with advanced or metastatic non-small cell lung cancer NSCLC that has a KRAS G12C mutation. The study includes a Phase 2 portion that assesses these treatments in patients with various PD-L1 tumor proportion scores TPS and a Phase 3 portion that compares Adagrasib plus pembrolizumab to pembrolizumab alone in patients with higher PD-L1 TPS 50%. The goal is to understand how these treatments work as first-line therapy in this patient population. Treatment involves Adagrasib administered orally twice daily BID either alone or combined with pembrolizumab, which is given intravenously at 200 mg every three weeks. Phase 2 includes three cohorts based on PD-L1 status and treatment type, while Phase 3 randomly assigns patients to receive either the combination or pembrolizumab alone. Patients with unresectable or metastatic squamous or nonsquamous NSCLC are included, with specific brain metastases criteria for Phase 3 participants. Participants will be monitored over periods of up to 22 months in Phase 2 and 36 months in Phase 3. Assessments include measuring treatment efficacy, safety, pharmacokinetics, quality of life, and tumor response using RECIST 1.1 criteria. Regular evaluations involve imaging, clinical exams, and patient-reported outcomes. The study aims to provide detailed information on treatment tolerability and effectiveness during and after therapy.

Researchers are investigating the safety and feasibility of combining pre-operative radiation therapy with Cyclin-Dependent Kinase 4 CDK46 inhibitors in women aged 60 and older diagnosed with hormone receptor positiveHER2 negative HRHER2- breast cancer. This phase 1b study focuses on understanding how well this combined treatment is tolerated and its potential benefits for this specific breast cancer subtype. Participants will receive abemaciclib at varying doses twice daily along with letrozole daily for three 28-day cycles before starting targeted radiation therapy. The study includes several parts initial combined drug treatment, followed by radiation therapy while continuing the drugs, additional cycles of the medications, and finally surgery. Biopsies and dose adjustments are part of the treatment plan to monitor safety and dosing. Throughout the study, participants will undergo detailed clinical assessments, imaging, laboratory tests, and biopsies to track treatment responses and possible side effects. Researchers will monitor safety by recording adverse events regularly over five years and evaluate outcomes such as residual cancer burden, post-operative complications, breast-conserving surgery rates, and disease-free survival. The total study participation includes long-term follow-up to assess both safety and treatment effects.