CAPTOR-BC: Comprehensive analysis of spatial, temporal and molecular biomarkers predicting response and resistance to first-line treatment with ribociclib + ET in HR+, HER2- advanced breast cancer.

person Peter A. Fasching Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany info_outline Peter A. Fasching, Sara Brucker, Hanna Huebner, Verena Thewes, Lea Louise Volmer, Andreas Daniel Hartkopf, Hans-Christian Kolberg, Benno Lex, Bahriye Aktas, Nina Ditsch, Lothar Haeberle, Katharina Seitz, Daniel Anetsberger, Naiba Nabieva, Christian Roos, Erik Belleville, Andreas Schneeweiss, Volkmar Mueller, Wolfgang Janni, Tanja N. Fehm

Authors person Peter A. Fasching Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany info_outline Peter A. Fasching, Sara Brucker, Hanna Huebner, Verena Thewes, Lea Louise Volmer, Andreas Daniel Hartkopf, Hans-Christian Kolberg, Benno Lex, Bahriye Aktas, Nina Ditsch, Lothar Haeberle, Katharina Seitz, Daniel Anetsberger, Naiba Nabieva, Christian Roos, Erik Belleville, Andreas Schneeweiss, Volkmar Mueller, Wolfgang Janni, Tanja N. Fehm Organizations Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany, Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany, National Center for Tumor Diseases (NCT), Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany, Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany, Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop, Germany, Department of Gynecology and Obstetrics, Kulmbach, Kulmbach, Germany, Department of Gynecology and Obstetrics, University Hospital Leipzig, Leipzig, Germany, Department of Gynecology and Obstetrics, University Hospital Augsburg, Augsburg, Germany, Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany, Novartis Pharma GmbH, Nuremberg, Germany, ClinSol GmbH & Co KG, Würzburg, Germany, Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany, Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany Abstract Disclosures Research Funding Other Institut fuer Frauengesundheit GmbH, Novartis Background: The combination of an oral CDK4/6 inhibitor with endocrine therapy (ET) has become the standard first-line therapy for women with advanced HR+ HER2- breast cancer. In this context, the broadest clinical trial data are available for ribociclib, a highly selective CDK4/6 inhibitor, with three phase III trials (MONALEESA-2, -3 and -7) consistently showing a significant overall survival benefit compared to ET monotherapy regardless of treatment line, menopausal status or combination partner. However, de novo or acquired resistance to CDK4/6 inhibitors does occur and biomarkers predicting treatment response or providing information on resistance mechanisms are only beginning to be understood. Comprehensive identification and validation of biomarkers before and during ribociclib therapy is needed to better understand mechanisms leading to disease progression, which will be the first step towards developing novel therapies and optimizing treatment sequences. Methods: CAPTOR-BC (NCT054552213) is a single-arm, open-label phase IV study evaluating the combination of ribociclib and ET according to SmPC in the first-line treatment of HR+ HER2- advanced breast cancer to identify and validate molecular and non-molecular biomarkers predictive of drug response and resistance. First patient first visit occurred in October 2022 and at least 1000 patients across more than 75 sites in Germany will be enrolled until October 2025. Progression-free survival (PFS) and overall survival (OS) at 12 months are the co-primary endpoints, quality of life (QoL) and toxicity are secondary endpoints. Exploratively, a comprehensive multi-omics biomarker discovery and validation program is integrated into the study: Besides tumor tissue, liquid biopsies profiling circulating tumor (ct)DNA, ctRNA, whole blood RNA, proteins from serum and plasma, and circulating immune cells will be evaluated before, during and after treatment or upon progression to determine correlations with PFS, OS, QoL and adverse events. Clinical trial information: NCT05452213.

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