Abstract PO1-19-05: COGNITION/-GUIDE – Implementation of Precision Oncology in Early High-Risk Breast Cancer

Abstract Background: The concept of precision oncology is nowadays increasingly implemented into clinical practice but is predominantly restricted to the metastatic setting limiting the benefits to prolongation of progression-free-survival (PFS). Implementation of precision oncology at an earlier disease stage with less tumor burden, heterogeneity and a higher capacity of tumor lesions to inform on the molecular tumor landscape holds the promise to impact cure rates. Methods: The prospective COGNITION/-GUIDE precision oncology platform encompasses the COGNITION diagnostic multi-omics biomarker screening platform (NCT05906407) linked to the multi-arm phase II COGNITION-GUIDE umbrella trial (NCT05332561). Based on a two-step consenting procedure, patients with early breast cancer (eBC) and poor response towards standard-of-care (SOC) neoadjuvant chemotherapy (NACT) are first enrolled into the COGNITION diagnostic platform. Residual bulk tumors are subjected to whole-genome- (WGS)/whole exome- (WES) and RNA-sequencing to enable streamlined detection of a rigorous biomarker-framework for subsequent genomics-guided arm allocation. Pilot analyses revealed that 78% (81/104) of high-risk tumors (TNBC or HER2+ BC with non-pCR or HR+/HER2- BC with non-pCR and CPS-EG score ≥ 3, or ypN+ and CPS-EG score ≥ 2) can be successfully sequenced and discussed within an interdisciplinary molecular tumor board. In 67% (70/104) eligible biomarker-profiles could be identified for potential biomarker-guided therapeutic intervention. In a second step, having completed all standard-of-care neoadjuvant and post-neoadjuvant treatments (except endocrine therapy, which can be administered simultaneously to the experimental therapy), patients can be enrolled into one of 6 biomarker-based arms in the COGNITION-GUIDE phase II trial (atezolizumab, inavolisib, ipatasertib, olaparib, sacituzumab govitecan or trastuzumab/pertuzumab). Primary end point is invasive disease-free survival (IDFS) at 4 years after surgery in the whole study population. Secondary endpoints are overall survival (OS), IDFS in each treatment arm, distant disease-free survival (DDFS) and patient-reported outcomes (PROs). Enrollment in COGNITION-GUIDE started in Q2/2023 and 240 patients will be enrolled in 5 German sites until Q2/2027. A comprehensive biomarker discovery program is integrated on longitudinal tumor tissue and liquid biopsies for exploratory analyses. Further clinical work and accrual will be reported at the meeting. Conclusion: The theranostic COGNITION/-GUIDE platform moves the concept of precision oncology to a potentially curative but still high-risk stage of eBC following SOC NACT. Hence, this novel application in the field of precision oncology harbours the prospect to increase cure rates. Citation Format: Verena Thewes, Luise Strassl, Marc Zapatka, Mario Hlevnjak, Constantin Pixberg, Christian Maurer, Katharina Smetanay, Carlo Fremd, Laura Michel, Sabine Heublein, Celina V. Wagner, Jan-Philip Suppelna, Lars Buschhorn, Albrecht Stenzinger, Renate Haidinger, Eva Schumacher-Wulf, Sibylle Loibl, Pauline Wimberger, Jens-Uwe Blohmer, Peter A. Fasching, Wolfgang Janni, Richard F. Schlenk, Peter Lichter, Andreas Schneeweiss. COGNITION/-GUIDE – Implementation of Precision Oncology in Early High-Risk Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-19-05.