Stockton

The study will assess the efficacy and safety of 2 dose regimens of pegozafermin compared to placebo for the treatment of liver fibrosis stage F2 or F3 in adult participants with MASH.

Randomised controlled study: Treatment phase: Patients will receive treatment with either acalabrutinib 100 mg po tablets bd (until unacceptable toxicity or progression) or investigator's choice of treatment (chlorambucil, venetoclax, ibrutinib, zanabrutinib, rituximab or Obinutuzumab etc). For the control arm the treatment type and duration will be defined by the PI prior to randomisation. Each treatment cycle is 28 days/4 weeks. Haematology visits (labs, physical exam), will be performed at the first day of each cycle for the first 8 cycles and every 4 cycles there after. Response assessment will be performed by the PI in accordance with modified iwCLL 2018 criteria every 4 cycles (16 weeks). Imaging and BM testing only as deemed appropriate by PI. Safety assessments will be performed at every visit. Cardiology assessments will be performed at the end of cycle 1 (C2D1) and 3 (C4D1) and thereafter every 4 cycles (16 weeks). These assessments will include: * A cardiology consult. * ECHO, 12-lead ECG and 24-hour Holter. * Cardiac biomarkers. * Any additional testing will be performed as clinically indicated. Cardiac MRI post-screening will be performed every year. Decisions for permanent withdrawal or modifications to treatment due to cardiac AEs will be made by PI after close consultation with the cardiologist. Post-Treatment Phase: Safety assessments Once treatment is discontinued due to any of the reasons mentioned above, a safety follow-up (SFU) will occur within 45 days of the last dose of treatment. This will occur regardless of the patient developing progressive disease or initiation a new anti-CLL therapy during that timespan. The evaluation will include: * Cardiology consult * Cardiac biomarkers * 12-lead ECG, ECHO and 24 hour Holter * Cardiac MRI (if not performed in the last 6 months). The subsequent safety assessments will continue until disease progression, WoC, death or termination of study whichever occurs first. These will mirror the in-treatment schedule, with cardiology consults including ECHO, ECG, cardiac biomarkers and 24 hour Holter performed every 16 weeks and yearly cardiac MRI. Once patient has progressive disease they will be contacted to assess survival status every 16 weeks. Response assessments Patients that discontinue treatment prior to progression will continue to be evaluated for disease progression every 16 weeks. The response assessment will be per iwCLL 2018 guidelines and will be performed by the PI. Bone marrow testing and imaging will continue to remain optional and per PI discretion. Once patient has progressive disease they will be contacted every 16 weeks for survival status and information on any new anti-cancer therapy until WoC, death, termination of study by Sponsor whichever occurs first.

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with intermediate-high or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy). The planned duration of treatment in either arm of the study is 7 years. Eligible patients must have intermediate-high or high risk of recurrence as defined by specified clinical and biologic criteria. Concurrent use of abemaciclib is permitted in both arms. The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), Distant relapse-free survival (DRFS), Overall survival (OS), Safety and Clinical Outcome Assessments (COAs). Patients will be followed for 10 years from randomization of the last patient.