Heilbronn , Neckar, Germany

A Global Phase III Study of Rilvegostomig or Pembrolizumab Monotherapy for First-Line Treatment of PD-L1-high Metastatic Non-small Cell Lung Cancer

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab as a 1L treatment for patients with mNSCLC whose tumors express PD-L1.

Revumenib in Combination With Azacitidine + Venetoclax in Patients NPM1-mutated or KMT2A-rearranged AML

Iberdomide Vs. Iberdomide Plus Isatuximab Maintenance Therapy Post ASCT in Newly Diagnosed Multiple Myeloma

Prospective, multicentre, randomised, parallel group, open, phase III clinical trial for a maintenance therapy, for patients who underwent an induction therapy and autologous stem cell transplantation in the GMMG-HD8/DSMM XIX trial. Investigational Medicinal Product: Iberdomid (oral), isatuximab (subcutaneous administration via a wearable injector system). Randomisation will be performed centrally by GMMG/DSMM offices after verification of the eligibility of the patient. At the time of study inclusion, randomization will be performed into arm A (iberdomide) or arm B (iberdomide + isatuximab). Randomization will be stratified by centrally assessed MRD negativity status (yes vs. no vs. unknown); assessed by NGF from BMA; sensitivity of 10^-5; independent of standard IMWG response) and number of HDM/ASCT (single vs. tandem). Patients randomized in arm A will receive 39 cycles of the drug iberdomide, a Cereblon E3 Ubiquitin Ligase Modulating Drug (CELMoD®) that shares structural similarities to the immunomodulatory compounds (IMiDs) such as thalidomide and lenalidomide. Each cycle will last for 29 days. Patients in arm B will receive the same the 39 cycles of iberdomide plus monoclonal anti-CD38 antibody isatuximab subcutaneously. In both arms, patients will receive 20 mg dexamethasone in cycle 1, on the same days as the isatuximab administration in Arm B. End of study will be after 36 months of the maintenance therapy. There is one primary objective: - Demonstration of superiority of iberdomide plus isatuximab compared to iberdomide with respect to bone marrow minimal residual disease (MRD) negativity rates (sensitivity 2x10^-6 via next-generation flow cytometry [NGF]) after two years of maintenance therapy. There is one key secondary objective: - PFS, defined as time from randomization to disease progression or death from any cause, whichever occurs first. Further secondary objectives are: - Rates of sustained MRD negativity (at sensitivity levels of 10-5 and 2x10^-6 via NGF from BMA) after 1, 2 and 3 years of maintenance therapy. - Conversion from MRD positive to negative (at sensitivity levels of 10^-5 and 2x10^-6 via NGF from BMA). - Rates of best overall response to treatment (BOR). - Rates of partial response (PR), very good partial response (VGPR), complete response (CR) and stringent complete response (sCR). - Time-to-next-treatment (TTNT). - PFS on subsequent line of therapy. - Overall survival (OS). - Improvement of IMWG response categories (PR, VGPR, CR, sCR). - Proportions of patients in both treatment arms maintaining BOR and CR from baseline. - Assessment of quality-of-life (QoL) via the EORTC-QLQC30, EORTC-QLQMY20, and EQ-5D-5L questionnaires.

A Phase III Study of Dato-DXd With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer

The primary objective of the study is to demonstrate superiority of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of PFS as assessed by BICR in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC. The study will be stratified based on geographic location (US/Canada/Europe vs. Dato-DXd monotherapy enrolling countries vs. rest of world), disease-free interval (DFI) history (de novo vs. prior DFI 6 to 12 months vs. prior DFI > 12 months), and prior PD-1/PD-L1 treatment for early stage TNBC (yes vs. no). This study aims to see if Dato-DXd with durvalumab allows patients to live longer without their breast cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy and pembrolizumab. This study is also looking to see how the treatment and the breast cancer affects patients' quality of life.

NeoAdj. Therapy Comparing Sacituzumab Govitecan (SG) vs. SG+Pembrolizumab in Low-risk, Triple-neg. EBC (ADAPT-TN-III)

About 15% of breast cancers lack both, expression of ER and PR receptors, and amplification/over-expression of HER2 receptors, and are thus described as triple negative breast cancer (TNBC). TNBC is known for poor prognosis, aggressive patterns of disease, and significant molecular heterogeneity. (Neo)adjuvant chemotherapy (NACT) is standard of care in all node-positive and in node-negative patients with a tumour size >5 mm according to current National Comprehensive Cancer Network (NCCN) guidelines. However, TNBC patients with lower stage disease do clearly have a better prognosis compared to more advanced stages. Patients with stage I-II node-negative disease have 3-5 year iDFS rates of 80-90% (with majority of relapses within the first three years) as shown in several trials. Our own results from the PlanB- and ADAPT-trials, and pooled analysis with SUCCESS C-trials show 3-year iDFS of 86-90% in node-negative TNBC with a tumour size < 3 cm. Although survival results appear much better in the lower vs. higher stages, there is a high clinical need in this most common group of TNBC patients in Western Europe and USA. In the neoadjuvant setting, it has been shown that the prognosis of patients with TNBC is strongly dependent on their response to NACT: Patients achieving pathological complete response (pCR), or a near pCR (an excellent response after NACT (residual cancer burden (RCB) score 0-1), in some studies do have an excellent prognosis that is not significantly different from that observed in other breast cancer subtypes. However, patients with a less responsive disease (i.e., with RCB Score 2-3) suffer from a significantly worse prognosis compared to non-TNBC. Chemotherapy in TNBC The optimal chemotherapy regimen for patients with TNBC remains to be identified. Standard anthracycline-taxane (A/T)-based NACT combinations render pCR rates between 25-50%. However, the survival impact of anthracyclines remains controversial due to conflicting results of different randomized trials. Adding carboplatin (carbo) to A/T-containing poly-NACT or use of dose-intensified poly-NACT significantly increases pCR-rates up to 49-60% in mostly stage II-III disease with conflicting survival results and higher toxicity. Hence, use of pragmatic taxane-carboplatin anthracycline-free combinations appears as an effective treatment option in TNBC instead of further treatment escalation. This probably is independent of the germline BRCA (gBRCA) status, due to its general chemo-predictive effect. Unfortunately, no prospective phase-III-data are available so far. However, indirect comparison between trials renders similar pCR rates in taxane-carboplatin based vs. A/T+/-carbo-based regimens in early TNBC. In the ADAPT-TN neoadjuvant trial, the taxane-carbo arm (12-week nab-paclitaxel (nab-pac)+carbo) was well tolerable (only 10% SAE-rate), highly effective (pCR, ypT0/is/ypN0, of 46%) and superior to the gemcitabine (gem)-arm (nab-pac+gem, pCR of 29%). In this study, omission of further chemotherapy was allowed in patients with pCR after 12 weeks of therapy and was not associated with decreased survival after 3 years [5] and longer follow up. Although a standard chemotherapy as well as optimal therapy duration are still to be defined, several studies are showing a comparable efficacy for longer vs. shorter adjuvant treatments in TNBC [3], as well as a similar efficacy regarding pCR in HR-negative (in contrast to HR-positive) early breast cancer (eBC) [26]. Moreover 6 vs. 4 cycles of the same chemotherapy (AC or pac weekly) yielded a similar survival outcome in eBC despite of HR-status. No such comparison regarding treatment duration is available for modern antibody-drug conjugates like sacituzumab govitecan (SG). Therefore, an examination of shorter (12 weeks vs. 18 weeks) regimen as neoadjuvant treatment appears to be a very promising strategy at least in patients with lower risk disease or in elderly patients, who do not qualify for polychemotherapy treatments. In the Keynote-522 trial combination of carboplatin/taxane-anthracycline NACT with the anti-PD1-antibody pembrolizumab (PEM) has been shown to be associated with a significantly higher pCR and clinically meaningful better EFS and a trend to better OS. Noteworthy only patients with more advanced stages IIa-III TNBC were included into the Keynote-522 trial. Although this effect was independent of clinically assessed nodal status, there is still some uncertainty on the optimal treatment in patients with clinical stage I. In the metastatic setting, SG as a Trop-2-antibody-drug-conjugate has been shown to be highly efficacious in severely pre-treated patients (all with A/T pre-treated tumours, most of them carboplatin and 1/3 also anti-PD1 pre-treated) compared to chemotherapy of investigator´s choice. Treatment with SG was associated with significant longer median PFS (5.5 vs. 1.7 months) and longer median OS (12.1 vs. 6.7 months). Objective response was dramatically higher in the SG group vs. treatment by physician´s choice group (34.9 vs. 4.7%), in particular in the 2nd-3rd-line therapy (40% vs. 4%). Moreover, Tropics-02 trial has shown higher efficacy of SG vs. chemotherapy of investigator´s choice in patients with HR-positive/HER2-negative metastatic breast cancer. In the neoadjuvant setting, recently presented results from the NeoSTAR trial show a promising pCR-rate of 30% and RCB 0-1-rate of 36% in TNBC patients with mostly stage II-III-disease (about 80%) after only 4 cycles of SG. The following clinical questions are of highest medical need 1. Can 12-18 weeks neoadjuvant treatment with SG alone or in combination with PEM be associated with comparable pCR-rates (but more favourable safety profile) as shown for polychemotherapy in TNBC patients at lower relapse risk in historical controls? 2. Can SG-based therapy, as the most promising agent in patients with chemo-resistant disease, be associated with a such better prognosis (measured by 3-year-iDFS) compared to historical controls, which would make a randomized phase III-trial obsolete?

Register Schweres Asthma - German Asthma Net e.V.

Sociodemographic parameters (e.g., gender, date of birth) and medical parameters (diagnosis, therapy) are entered in the register. In addition, data on lung function, laboratory values (IgE and eosinophil granulocytes), asthma control (symptoms, nocturnal awakenings, on-demand medication, exacerbations), smoking status, and concomitant therapy (inhalable corticosteroids, bronchodilators, and systemic steroids) are collected. This information will be collected at the baseline visit, and then once a year at a follow up visit, for fifteen years. Participants will be assigned a unique study ID to protect the confidentiality of their personal health care information. Personal data and register data are on separate servers and thus meet the requirements of data protection. The primary purpose is to establish a clinical registry for patients with severe asthma. The number of patients with severe asthma at a single center or practice is usually small, so several centers (clinics and practices) in Germany have joined together to form the German Asthma Net e.V. to optimize the diagnostic evaluation and treatment of patients with severe asthma.

BioPearl™ Microspheres Loaded With Doxorubicin for the Treatment of Unresectable Hepatocellular Carcinoma (HCC)

This is a prospective, single arm, multi-centre, post-market clinical follow-up study to further assess safety and efficacy in 50 subjects with unresectable HCC treated with BioPearl™ microspheres loaded with Doxorubicin. All subjects will undergo clinical follow-up until disease progression and/or next treatment option, after which subjects will be followed for survival. Subjects will be followed up to a maximum of 18 months. An intermediate analysis will take place during enrollment period on safety and technical success to support regulatory requirements.

Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients

This is a prospective, multicenter, phase IV, one-arm, open-label clinical trial investigating patients treated with ribociclib and standard of care endocrine therapy for hormone receptor positive (HR+) / human epidermal growth factor receptor negative (HER2-) advanced breast cancer in the first therapy line. Patients eligible for this trial will receive on-label ribociclib according to Summary of Product Characteristics (SmPC) and as well as the specified inclusion/exclusion criteria. The survival rates for progression-free survival (PFS) and overall survival (OS) at month 12 are the co-primary objectives. Quality of life and toxicity are secondary objectives. Additionally, there is a comprehensive biomarker discovery and validation program included into the study. A total of 1000 patients are planned to be enrolled into this trial in 75 trial sites in Germany. Biomarkers will be evaluated before, during and after treatment or at progression. A comprehensive biospecimens sampling will be done to enable translational research projects and evaluation of potential biomarkers within circulation tumor desoxyribonucleic acid (ctDNA), circulating tumor ribonucleic acid (ctRNA), formaldehyde-fixed paraffin-embedded tissue (FFPE) tissue, Serum, Plasma and circulating immune cells

ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation

A Study to Assess Disease Activity in Adolescent and Adult Participants With Atopic Dermatitis Who Receive Oral Upadacitinib Tablets in a Real-World Setting