Niefern-oeschelbronn, Germany

A Study to Compare the Efficacy, Safety, Pharmacokinetics, and Immunogenicity Between SB27 and Keytruda in Subjects With Metastatic Non-squamous Non-small Cell Lung Cancer

An Open-label Study to Assess Safety and Efficacy of SZC in Paediatric Patients With Hyperkalaemia

Protocol title: An open-label study to assess safety and efficacy of SZC in paediatric patients with hyperkalaemia Rationale: Sodium zirconium cyclosilicate has been shown to be effective and safe in adults for the treatment of hyperkalaemia, and therefore it is expected to be beneficial in children. This study will evaluate the efficacy, safety and tolerability of sodium zirconium cyclosilicate for the treatment of hyperkalaemia in children <18 years of age Primary Objective: Correction phase (CP) primary objective: 1. To evaluate the ability to achieve normokalaemia during the CP when initiating treatment with SZC of different dose levels (DLs) in children with hyperkalaemia 28-day Maintenance Phase (MP) primary objective: 2. To evaluate the ability to maintain normokalaemia during the MP when continuing SZC treatment in children achieving normokalaemia Secondary Objectives: All phases secondary objective: 3. To evaluate the change in S-K+ in children treated with SZC MP secondary objectives: 4. To evaluate change in serum aldosterone levels in children treated with SZC during the MP 5. To evaluate change in serum electrolytes (including bicarbonate), spot urinary pH and urinary electrolytes levels in children treated with SZC during the MP Long-term MP (LTMP) secondary objectives: 6. To evaluate the ability of maintaining normokalaemia in children treated with SZC during the LTMP Safety Objective: 7. To evaluate the safety and tolerability of SZC in the 3 phases (CP, MP, and LTMP) Tertiary/Exploratory: 8. To evaluate the acceptability and palatability of SZC through the study Overall design: This is a Phase 3, international, multi-centre, open-label study assessing different doses of SZC. The population to be studied is hyperkalaemic children < 18 years. Dosing will mirror the regimen approved for adults using body weight equivalent doses. Enrolment will start in 2 cohorts, ages 6 to < 12 years and 12 to < 18 years. After review of accumulated data, the independent Data Monitoring Committee (iDMC) will recommend whether to open enrolment in the ages 2 to < 6 years cohort and later in the ages 0 to < 2 years cohort. The study will be conducted in approximately 11 countries and 46 sites. All eligible participants with hyperkalaemia will enter an open-label Correction Phase (CP) receiving a fixed dose of SZC three times daily (TID) for up to 3 days until normokalaemia is achieved. Within each age cohorts 2 to < 18 years, initial participants will be allocated to the dose level (DL) based on body weight equivalent to an adult 5 g TID. After recommendation of higher DLs by the iDMC, subsequent participants may be allocated in the CP to on body weight equivalent to an adult 10 g TID and then potentially on body weight equivalent to an adult 15 g TID. All participants in the ages 0 to < 2 years cohort will be assigned to the same DL which will be decided based on data from older age cohorts. Participants who successfully achieve normokalaemia in the CP will enter a 28-day open-label Maintenance Phase (MP), which will be initiated with once daily administration of the dose received TID in the CP. During MP, the Investigator is able to titrate the dose up or down in the range 2.5 g to 15 g body weight equivalent to maintain normokalaemia. The MP is followed by the option for participants to continue the study in a long-term maintenance phase (LTMP) where the same titration regimen is used as in MP, but with monthly visits. Study period: Estimated date of first participant enter the CP Q4 2018. Estimated date of last participant completed 27 December 2024. Number of participants: This study aims to enter into CP a total of approximately 140 participants with hyperkalaemia. Of these, approximately 85 participants are expected to have moderate to severe hyperkalaemia. Enrolment will continue until at least 54 participants with moderate to severe hyperkalaemia have entered the MP and 45 participants with moderate to severe hyperkalaemia have completed the MP. A maximum of 55 participants with mild hyperkalaemia will enter the CP. In addition, there are minimum requirements for participants in each age cohort Duration: Study duration is approximately 28 weeks including up to 3 days of correction treatment, followed by maintenance treatment for 28 days, a LTMP for up to 22 weeks, and a safety follow-up visit 1 week after the last dose. Treatments and treatment duration: Treatment will include 3 phases: the CP, MP, and LTMP. All age cohorts are eligible to participate in all phases of the study. The 3 treatment phases are specified below: Correction phase (CP): All eligible participants with hyperkalaemia will enter an open-label Correction Phase (CP) receiving a fixed dose of SZC three times daily (TID) for up to 3 days until normokalaemia is achieved. Within each age cohorts 2 to < 18 years, initial participants will be allocated to the dose level (DL) 5 g TID. After recommendation of higher DLs by the iDMC, subsequent participants may be allocated in the CP to 10 g TID and then potentially 15 g TID. All participants in the ages 0 to < 2 years cohort will be assigned to the same DL which will be decided based on data from older age cohorts. Maintenance phase (MP): Participants who successfully achieve normokalaemia in the CP will enter a 28-day open-label Maintenance Phase (MP), which will be initiated with once daily administration of the dose received TID in the CP. During MP, the Investigator is able to titrate the dose up or down in the range 2.5 g to 15 g body weight equivalent to maintain normokalaemia. Long term Maintenance Phase (LTMP): For participants who, at the end of MP, are normokalaemic or hyperkalaemic without being on maximum dose, the MP is followed by the option to continue the study in a long term maintenance phase (LTMP) where the same titration regimen is used as in MP. Data Monitoring Committee: The iDMC will recommend on the opening of dose levels during the CP after reviewing all available data. Additionally, iDMC will recommend whether and when enrolment in the ages 0 to < 6 years cohorts will begin, and will also evaluate emerging safety data during all phases of the study. Statistical methods: Objectives will be evaluated based on analysis populations corresponding to each study phase. Analysis sets are defined for each phase as the set of all participants who transitioned from previous phase and who received at least one dose of SZC during the phase. Primary assessments of the primary objectives, the probability to achieve and maintain normokalaemia when treated with SZC, will be based on point estimates together with 95% confidence intervals (CIs) from generalised linear models (repeated measures model for the MP). The secondary objective of change in S-K+ over time will be evaluated using a repeated measures linear model. Additional analyses, including analyses for other secondary objectives, will be done descriptively. In general, data will be analysed in the total analysis population, within each age cohort and, for the CP, within adult body weight equivalent dose-level, as appropriate. An interim read-out may be conducted.

A Study of Milvexian in Participants After an Acute Ischemic Stroke or High-Risk Transient Ischemic Attack- LIBREXIA-STROKE

NIS Study Determining Prevalence of HER2-low in Metastatic Breast Cancer Patients

Multicenter, noninterventional, retrospective study, aimed to determine the prevalence of HER2-low and HER2>0<1+ by rescoring of archived IHC-stained FFPE slides for HER2 in patients previously identified as having HER2-negative locally-advanced or mBC who progressed on any systemic anticancer therapy.The study will also describe the baseline sociodemographic and clinicopathological characteristics, treatment patterns, clinical outcomes and concordance between historical IHC status and rescored IHC status of archived IHC-stained FFPE slides. The study will not have any study-specific patient visits, procedures, or a longitudinal follow-up. All available data will be extracted from patients' medical records. The study will consist of 2 components: rescoring of archived IHC-stained FFPE slides and secondary data collection from patients' medical records. Human epidermal growth factor receptor 2 IHC historical scores, HER2 rescoring results of archived IHC-stained FFPE slides by qualified laboratory (local and/or independent central laboratory), other biomarker testing results based on historical testing and/or testing of archived tissue samples when available. The data on different types of treatment received by the patients and sociodemographics and clinicopathological characteristics will be extracted from patients' medical records from the date of diagnosis of HER2-negative BC up to the date of data extraction. The patients identified for the current study will be a convenience sample of all patients in the relevant electronic health record/electronic medical record databases and biobanks who meet the inclusion and exclusion criteria; no a priori power analysis will be conducted. The study aims to capture approximately minimal 150 to 200 HER2-negative mBC patients per participating country/cluster, in order to generate data on 2100 to 2700 patients overall, with the aim to identify approximately 1050 HER2-low patients (at least 600 patients in Asia cohort and 450 patients in Latin America [LATAM] cohort) for analysis, subject to revision based on preliminary data analysis. Clinical outcomes will be assessed as per the HER2 subsets identified after rescoring (HER2 low-IHC1+ or IHC2+/ISH-, HER2 IHC>0<1+, HER2 null, and HER2 zero-HER2 IHC>0<1+ and HER2 null). The study will be conducted in 8 Asian countries including Hong Kong, India, Indonesia, Malaysia, Philippines, Thailand, Singapore, and Vietnam and 6 Latin American (LATAM) countries including Argentina, Brazil, Chile, Dominican Republic, Mexico, and Panamá. Regions and countries may be added based on feasibility assessment as per AstraZeneca's standard operating procedures. A total of approximately 2100 to 2700 patients with a confirmed diagnosis of HER2-negative, locally-advanced or mBC regardless of HR status between 01 January 2019 and 31 December 2022 with the availability of medical records of at least 12 months of follow-up data (from the index date), and deemed eligible as per the study eligibility criteria will be enrolled in the study at approximately 28-58 study sites. The study protocol and informed consent form (ICF) will be approved by local Institutional Review Boards (IRBs)/(Institutional) Ethics Committees (IECs) before the commencement of recruitment.

A Study of Belrestotug Plus Dostarlimab Compared With Placebo Plus Pembrolizumab in Previously Untreated Participants With Programmed Death Ligand 1 (PD-L1) High Non-small-cell Lung Cancer (NSCLC)