Mirano

Researchers are studying women who carry mutations in the BRCA1 or BRCA2 genes, which increase the risk of developing breast and ovarian cancers. Despite many studies over the past two decades, the best ways to manage these mutation carriers are still not fully established. In Italy, about 140,000 to 150,000 individuals carry these mutations, and it is estimated that 87% of women with these mutations will develop a genetically linked tumor during their lifetime. Approximately 20% of ovarian cancer cases in Italy each year have a genetic origin and could benefit from preventive approaches. Currently, there is no national prospective data collection specifically for women with BRCA mutations in Italy.

Researchers are evaluating the safety and effectiveness of mirvetuximab soravtansine combined with bevacizumab as maintenance therapy in adult women with platinum-sensitive ovarian, primary peritoneal, or fallopian tube cancers that have high folate receptor-alpha (FRα) expression. This Phase 3, multicenter, open-label study focuses on patients who have not progressed after second-line platinum-based chemotherapy plus bevacizumab. Participants must have tumors confirmed as FRα-positive using the Ventana FOLR1 assay. Participants will be assigned to receive either mirvetuximab soravtansine at 6.0 mg/kg adjusted ideal body weight plus bevacizumab at 15 mg/kg every 3 weeks, or bevacizumab alone at 15 mg/kg every 3 weeks. Mirvetuximab soravtansine is an investigational antibody drug conjugate designed to selectively kill cancer cells expressing FRα. The treatment is given as maintenance therapy following prior platinum-based chemotherapy and bevacizumab. During the study, participants will undergo regular assessments to monitor progression-free survival for up to 4 years. Researchers will evaluate disease status and safety through clinical evaluations. Participants will also need to adhere to contraceptive requirements during treatment and for several months after. The study aims to understand how well the treatment combination controls cancer without progression and to assess its safety profile over time.

Researchers are evaluating advanced breast cancer patients with hormone receptor-positive, HER2-negative (HR+/HER2-) disease who are treated with first-line CDK4/6 inhibitors combined with endocrine therapy. The PALMARES-2 study is a multicenter, retrospective and prospective observational study aiming to gather real-world evidence on the outcomes of these treatments. The study collects diverse data types including clinical records, medical images, and biological samples to better understand patient responses and treatment effects. The study includes several sub-studies with different goals: one collects real-world clinical data to compare overall survival between three CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib); another assesses safety by collecting data on comorbidities, medications, and toxicities; additional sub-studies gather imaging and tumor samples to build predictive models using multi-omics analyses; and a final sub-study examines treatment lines after progression to support decision-making. All patients receive one of the three CDK4/6 inhibitors in combination with endocrine therapy as their first-line treatment. Participants contribute by providing clinical data, imaging scans like CT and PET, tumor samples, and biological data for analysis. Researchers monitor overall survival from the start of first-line treatment up to 120 months. Safety and toxicity are tracked, and predictive models are developed using collected data. The study design allows long-term follow-up to assess treatment outcomes, side effects, and response to subsequent therapies, providing comprehensive insights into managing advanced HR+/HER2- breast cancer.

Researchers are evaluating treatment options for patients with metastatic colorectal cancer (mCRC) who have a specific genetic profile: RAS/BRAF wild type in tumor tissue but RAS mutations detected in liquid biopsy. This phase III randomized study aims to determine whether first-line treatment with bevacizumab (an anti-VEGF antibody) plus chemotherapy (FOLFIRI) improves progression-free survival (PFS) compared to the standard treatment with cetuximab (an anti-EGFR antibody) plus FOLFIRI. The study also investigates if switching treatment to bevacizumab plus FOLFIRI upon detection of RAS mutations in liquid biopsy during cetuximab treatment, without clinical or radiological disease progression, affects PFS. Participants with RAS mutations detected at the first liquid biopsy are randomly assigned in a 1:1 ratio to receive either FOLFIRI plus cetuximab or FOLFIRI plus bevacizumab. Those with RAS wild type at first biopsy receive FOLFIRI plus cetuximab for up to 8 cycles outside the study protocol. After 4 months, a second liquid biopsy is performed, and if RAS mutations appear without disease progression, patients are again randomized to continue cetuximab or switch to bevacizumab. Treatment continues until disease progresses, unacceptable side effects occur, consent is withdrawn, or safety concerns arise. Throughout the study, plasma samples are analyzed for KRAS, NRAS, and BRAF V600 mutations using the Idylla system, and later by next generation sequencing to explore tumor heterogeneity and its relation to patient outcomes. Researchers will monitor progression-free survival for up to 36 months from randomization. This study seeks to identify the most effective monoclonal antibody therapy for this patient group and assess the clinical utility of liquid biopsy combined with tissue analysis for detecting mutations.

Researchers are evaluating the drug INCB123667 compared to chemotherapy chosen by investigators in women with platinum-resistant ovarian cancer that shows overexpression of cyclin E1. This Phase 3, open-label study focuses on participants with high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who have developed resistance to platinum-based treatments. The goal is to observe how these treatments affect progression-free survival and overall survival over a period of up to two years. Participants will receive either oral INCB123667 tablets or chemotherapy selected by their investigator based on protocol guidelines. The study includes women who have had between one and four prior lines of systemic therapy after initial diagnosis and have measurable disease according to RECIST criteria. Prior treatments should include bevacizumab and mirvetuximab soravtansine when appropriate. Archival tumor tissue or a fresh biopsy is required before treatment. During the study, participants will be closely monitored through various assessments to measure treatment outcomes and safety. Researchers will track progression-free survival and overall survival up to two years, evaluating the effectiveness of the treatments. The study excludes participants with certain cancer histologies, uncontrolled cardiac issues, active brain metastases, other progressing cancers, or significant gastrointestinal problems. The total duration includes treatment and follow-up evaluations as defined in the protocol.

Researchers are evaluating the long-term clinical and instrumental response to Cardiac Contractility Modulation (CCM) therapy in adults with symptomatic heart failure caused by systolic left ventricular dysfunction, despite receiving optimal medical treatment. This observational cohort study includes both retrospective and prospective aspects. It aims to determine the proportion of patients who experience improvement in their New York Heart Association (NYHA) class by at least one level after 12 months, reductions in hospitalizations and emergency visits, changes in quality of life using the Minnesota Living with Heart Failure Questionnaire, walking distance improvements, and differences in NT-proBNP levels. Participants either already have or will receive the CCM device called "OPTIMIZER Smart Mini," which is implanted with leads in the heart's right ventricle and optionally the right atrium. This programmable implantable pulse generator delivers electrical impulses to improve heart function. The device is intended for patients over 18 years with symptomatic heart failure and reduced left ventricular function who have not responded sufficiently to medical therapy. The study evaluates responses following implantation, guided by preimplantation low-dose Dobutamine stress echocardiography. During the study, participants' clinical status and heart function are monitored through echocardiographic tests, quality-of-life questionnaires, and walking tests over a 12-month follow-up. Researchers track hospitalizations, emergency visits, and biomarker levels as well. The primary outcome is the change in NYHA class from enrollment to study end. Safety and effectiveness data are collected as part of participants' routine medical care, with the goal of better understanding who benefits most from CCM therapy.