Wasserburg Am Inn

CLL is the most frequent leukemia in industrialized countries. International guidelines agree on diagnosis and management of this disease. The clinical course of CLL is highly variable and can be predicted by clinical staging (according to Rai and Binet) as well as genetic, serum markers and risk models. This study is designed for a randomized comparison of two different, non-chemotherapeutic and fixed-duration modalities for patients with high risk chronic lymphocytic leukemia (CLL) and addresses a high medical need, since high risk-CLL represents a so far incurable, aggressive cancer. The high risk-group of CLL patients can be identified by molecular characteristics, allowing the inclusion of a clearly described group of patients: 17p-deletion, TP53-mutation and/or complex karyotype.TP53 defects are the strongest prognostic factors for non-response to chemotherapy. Patients harboring TP53 defects should be treated with chemotherapy-free regimens. Complex karyotype (CKT), defined as the presence of three or more chromosomal aberrations in two or more metaphases is associated with a poorer outcome in various hematologic malignancies, including chronic lymphocytic leukemia (CLL). In CLL, CKT is one of several well established adverse prognostic factors, comparable to 17p-deletion, TP53-mutation or unmutated IGHV status. Depending on age and prior exposure to chemotherapy, 10-30% of patients with CLL exhibit CKT. A broad body of evidence has suggested a predictive prognostic value of CKT. Despite considerable advances with chemoimmunotherapy in the treatment of frontline as well as relapsed/refractory (r/r) CLL, outcome of patients with CKT remains poor. To date, a randomized comparison to optimize the treatment of patients with high risk disease defined as either the presence of TP53 aberrations or CKT, by novel agents has not been performed. Patients with high risk CLL (TP53-defects and/or CKT) have a poor outcome with chemoimmunotherapy and do not benefit to the same extent from approved regimen such as continuous treatment of ibrutinib or 12 months treatment with obinutuzumab plus venetoclax. Monotherapy with BTK-inhibitor is less effective in those patients as compared with patients without high risk disease. Venetoclax combined with the anti-CD20 monoclonal antibody obinutuzumab offers a highly effective fixed-duration treatment option with a manageable toxicity profile. The recent results of the CLL14 study define a new standard of a fixed 12-months treatment with obinutuzumab and venetoclax in previously untreated patients yielding a major benefit also for patients with high risk disease as compared to chemoimmunotherapy. However, high risk patients appear to progress earlier than low risk patients and the therapy is not clearly curative so far. Acalabrutinib is a second generation, selective BTK inhibitor which has shown promising overall response rates in patients with relapsed CLL or patients intolerant to ibrutinib. The development of acalabrutinib focussed on minimization of off-target activity. Results of a three-arm study investigating the combination of acalabrutinib plus obinutuzumab versus acalabrutinib alone versus chlorambucil plus obinutuzumab (NCT02475681) showed a substantial improvement of PFS for the combination arm and the monotherapy versus the standard chemoimmunotherapy regimen. The addition of a BTK-inhibitor, such as acalabrutinib to obinutuzumab and venetoclax has the potential to result in a better outcome, because synergistic effects have been reported between BTK inhibitors and B-cell lymphoma 2 (BCL-2) inhibitors or for BCL-2 inhibitors and monoclonal antibodies. Synergistic effects, which are expected to reduce early progressions or insufficient responses, are in particular important for this high risk population. The triple combination of acalabrutinib, obinutuzumab (or rituximab) and venetoclax has been investigated in a phase 1 b- study and had a tolerable safety profile with minimal to no drug-drug interactions, results of a phase 2 trial studying the same combination showed that the triple combination was highly active with 78% undetectable MRD levels in the bone marrow . Currently, the GCLLSG conducts phase 2 studies, investigating a triple combination consisting of BTK- and Bcl2-inhibitors and monoclonal antibodies (CLL2GIVe: NCT02758665; CLL2BAAG: NCT03787264) and a large phase 3 trial with one experimental arm with a triple combination (CLL13, NCT02950051) but results are not yet published. Acalabrutinib, venetoclax and obinutuzumab is now being studied in a registrational phase 3 trial CL-311 (NCT03836261) against the current standard of chemoimmunotherapy (fludarabine/cyclophosphamide/rituximab (FCR), bendamustine/rituximab (BR) in patients without 17p-deletion or TP53-mutation. Acalabrutinib is indicated in Germany as monotherapy or in combination with obinutuzumab for the treatment of adult patients with treatment-naive chronic lymphocytic leukemia (CLL) and as monotherapy for the treatment of adult patients with relapsed chronic lymphocytic leukemia (CLL).

The MINERVA Trial aims to evaluate safety, efficacy and quality of life (QoL) for the combination of Abemaciclib with an Aromatase Inhibitor or Fulvestrant in pre- and postmenopausal patients with metastatic hormone receptor positive HER2 negative breast cancer in the first line setting. Side effect monitoring and patient reported outcomes will be captured using the web- and app-based CANKADO digital health application. Via this user-friendly tool the patients can document their therapy side effects (e.g. diarrhea) and outcomes on a day-to-day basis. The capturing of side effects using the digital health application will be done additionally to the regular AE documentation. Furthermore, translational research objectives of this trial include the investigation of biomarkers (ct-DNA, germline DNA) to evaluate whether they can give insights into the reasons for response, intrinsic or acquired resistance to the combined endocrine

Eligible patients will be those patients with newly diagnosed, histologically confirmed, advanced (FIGO stage III/IV, except FIGO stage IIIA2 without nodal involvement) invasive high grade non-mucinous, non-clear cell epithelial ovarian cancer, peritoneal cancer, or fallopian tube cancer, who have either undergone upfront primary surgery or plan to undergo chemotherapy with interval debulking surgery (IDS). In addition, patients should not have any medical contraindications that would exclude treatment with bevacizumab and/or niraparib. All eligible patients will receive the first cycle of chemotherapy (carboplatin area under curve \[AUC\] 5 and paclitaxel 175 mg/m²) as part of Study Run-In-Period (cycle 1). In parallel, central laboratory will determine the breast cancer (BRCA) status in tumor tissue (tBRCA). All patients with a valid central tBRCA test result will be randomized within 3 days prior to day 1 of cycle 2 in a 1:1 ratio in the following treatment arms: Arm 1: Patients will receive further 5 cycles of carboplatin and paclitaxel q21d followed by niraparib once daily for up to a total of 3 years Arm 2: Patients will receive further 5 cycles of carboplatin and paclitaxel plus bevacizumab q21d followed by bevacizumab q21d (for up to 1 year) and niraparib once daily for up to a total of 3 years. The study aims to investigate, if the treatment strategy of carboplatin / paclitaxel / bevacizumab / niraparib is superior to the treatment of carboplatin / paclitaxel / niraparib-Inhibitor in an all-comer population.

This is a multi-center, prospective, non-interventional study (NIS) to collect real-world clinical and PRO data in patients with primary advanced (FIGO stage III or IV) or recurrent EC receiving 1L CPD followed by maintenance therapy with durvalumab (DNA mismatch repair deficient; dMMR cohort) or durvalumab and olaparib (DNA mismatch repair proficient, pMMR cohort) in accordance with the applicable SmPC within routine clinical practice. Following surgery and/or radiation (if applicable) the decision to initiate 1L CPD followed by durvalumab or durvalumab and olaparib is made in a shared decision between the patient and the treating physician as part of routine care outside of and independent of this study. The aim of the NIS is to describe the outcomes including effectiveness, safety and PRO of patients with primary advanced and recurrent EC treated with the two approved 1L regimens of CPD followed by durvalumab maintenance and CPD followed by durvalumab and olaparib maintenance in Germany. The study also aims to better understand characteristics of patients with primary advanced or recurrent EC that benefit from maintenance therapy with durvalumab or durvalumab and olaparib.

This prospective non-interventional study is intended to generate new data and insights into first-line (1L) treatment of newly diagnosed advanced high-grade epithelial Ovarian cancer (OC) in Germany relevant for patients, physicians and payers. It will capture the influence of 1L Poly ADP ribose polymerase inhibitor (PARPi) maintenance treatment (MTX) on medical routine in Germany, especially on: * outcome of the 3-steps 1L treatment phase (including surgery, Chemotherapy (CTX) and MTX) including the potential of patients with primary advanced OC to be cured, * patient's follow-up (FU) during and after MTX therapy, * patient-reported outcomes (PROs), experiences and needs, * physician's experience, * BRCA/HRD and genomic scar testing behavior at diagnosis/during 1L therapy, * patient selection for different 1L systemic treatment approaches, * use and safety of drugs, * treatment sequence in case of recurrence