Abstract PS5-07-03: Capitrue, capicorn, and capitana: three phase iiib studies to evaluate the use of capivasertib in combination with fulvestrant in patients with advanced breast cancer who have relapsed/progressed on endocrine therapy and cdk4/6 in

Abstract HR+/HER2− advanced breast cancer (ABC) remains a therapeutic challenge due to resistance to endocrine therapy (ET) and CDK4/6 inhibitors. Alterations in the PI3K/AKT pathway, including PIK3CA, AKT1, and PTEN alterations, are associated with poor prognosis and with the activation of PI3K-AKT signaling. Capivasertib, a selective AKT inhibitor, improved progression free survival (PFS) statistically significant and clinically meaningful in the CAPItello291 trial (NCT04305496), when combined with fulvestrant, both in the overall population (PFS in Capivasertib+fulvestrant group 7.2 vs 3.6 in placebo+fulvestrant group, HR=0.60) and in patients with PIK3CA/AKT1/PTEN altered tumors (PFS in Capivasertib+fulvestrant group 7.3 vs 3.1 in placebo+fulvestrant group, HR=0.50). Building on these findings, the CAPItrue (China-NCT06635447), CAPIcorn (Germany, Belgium, and Portugal), and CAPItana (Spain-NCT06764186) trials aim to evaluate the real-world (RW) effectiveness and safety in five countries, addressing the need for region specific data to inform clinical practice and treatment strategies in diverse healthcare settings. Based on CAPItello291 trial protocol, the CAPItrue (China), CAPIcorn (Germany, Belgium, and Portugal), and CAPItana (Spain) studies are Phase IIIb, single arm, multicenter trials designed to evaluate in a RW setting the effectiveness and safety of the combination. All studies administer capivasertib 400 mg BID (4 days on, 3 days off) together with fulvestrant (FUL) 500 mg IM every 28 days, with a loading dose given on Day 15 of Cycle 1, in patients with HR+/HER2- advanced breast cancer and alterations in PIK3CA/AKT1/PTEN who have progressed on ET in combination with CDK4/6 inhibitors. CAPItrue uniquely allows inclusion of patients without PI3K/AKT pathway alterations. Inclusion criteria allow for up to two previous lines of ET (and one line of chemotherapy for advanced disease), include diabetic or prediabetic patients (HbA1c <8%). Eligibility criteria have been expanded to include with prior SERDs treatment in the three studies, and specifically for CAPItana up to 20% of patients with an ECOG PS2. In the three studies, the primary endpoint is time to next/first subsequent treatment (TTNT/TFST) as the main measure of effectiveness. CAPItrue includes two cohorts: patients without prior FUL (cohort 1) and with 1L FUL (cohort2, not included in CAPItello-291). Regarding health-related quality of life, different questionnaires are employed according to the region: the EORTC QLQ BR42 in Spain, FACT G in Germany, and an adaptation of the EORTC QLQ BR23 and EORTC QLQ-C30 in China, reflecting local practices. To date, in the CAPItrue study, 81 sites have been activated, and 203 out of 560 patients have been enrolled (First Subject In (FSI): 26 Sep 2024 Huizhou Central People's Hospital). In Spain, 17 sites are active with 53 out of 100 patients enrolled ((FSI: 7Jan2025 in Hospital Universitario Miguel Servet). Meanwhile, CAPIcorn plans to open 23 sites (15 in Germany, 5 in Belgium, and 3 in Portugal) with an expected recruitment of 250 patients. The parallel execution of these studies across five countries (China, Germany, Belgium, Portugal, and Spain) will provide robust, region-specific RW data from approximately 910 patients. This will enable the adaptation of CAPItello-291 findings to diverse clinical practices and contribute to the development of globally and locally relevant oncology strategies. A joint analysis of the data gathered from the three studies is planned. Citation Format: R. Sánchez Bayona, S. Kuemmel, Z. Jiang, M. Oliveira, O. Gluz, S. Zhang, T. Pascual, R. Wuerstlein, P. Yuan, M. Vidal Losada, M. Graeser, B. Zhao, F. Henao Carrasco, R. Kates, F. Ju, G. Viñas, C. zu Eulenburg, Z. Chen, A. Perelló Martorell, E. de Azambuja, F. Fu, A. Antón, H. Gouveia, C. Hao, C. San Millán Martín, T. Schinkoethe, Y. He, Z. Jian, C. Saura, N. Harbeck. Capitrue, capicorn, and capitana: three phase iiib studies to evaluate the use of capivasertib in combination with fulvestrant in patients with advanced breast cancer who have relapsed/progressed on endocrine therapy and cdk4/6 inhibitors reflecting real-world clinical practice in china, germany, belgium, portugal and spain. [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-07-03.