Abstract PS5-07-16: Cappa, a phase 2 study to evaluate capecitabine plus pembrolizumab as post-operative adjuvant therapy for triple-negative breast cancer with residual disease after neoadjuvant chemo-immunotherapy

Abstract The KEYNOTE-522 trial demonstrated the benefit of adding pembrolizumab to neoadjuvant chemotherapy in patients with stage II-III triple-negative breast cancer (TNBC), showing improvements in both pathological complete response (pCR) rates and overall survival. However, a key limitation of the KEYNOTE-522 trial is that it did not incorporate the use of post-neoadjuvant capecitabine for patients who did not achieve a pCR, despite evidence that capecitabine improves survival in this population. Although post-neoadjuvant capecitabine combined with pembrolizumab is commonly discussed, there is no prospective data confirming its efficacy and tolerance in clinical practice. CAPPA (NCT0597386) is a phase II, open-label, multicenter trial evaluating the addition of capecitabine to pembrolizumab as adjuvant therapy in patients with stage II-IIIb TNBC and residual disease after neoadjuvant chemo-immunotherapy. Main inclusion criteria are: (i) Histologically confirmed TNBC, defined as HER2-negative (according to ASCO/CAP criteria) and <10% of cells staining positive for ER and PR by IHC; (ii) Patients who received standard neoadjuvant chemo-immunotherapy (minimum of 6 cycles); (iii) Absence of pCR, defined as RCB class I-III. This trial includes two distinct cohorts: (i) A prospective experimental cohort (N=220), patients will receive capecitabine (1000 mg/m2 BID, 14 days on and 7 days off) combined with pembrolizumab (200 mg every 3 weeks) for 6 months. Capecitabine is reduced at a dose of 825 mg/m2 BID during radiotherapy, performed as per standard practice, if indicated. (ii) An external cohort (N = 220), reflecting the treatment received in the KN-522 trial, will be enrolled in an ambispective manner and will include patients treated with pembrolizumab as part of standard adjuvant treatment, with similar eligibility criteria. The primary endpoint is the 2-year invasive disease-free survival (iDFS) rate. Secondary endpoints include distant disease-free survival (DDFS), overall survival (OS), and safety. Ancillary studies will be conducted on tumor biopsies, surgical specimens, and blood samples. The first patient was enrolled in March 2025. As of July 9, N=14 and 17 pts have been included in the experimental and external cohort, respectively. The inclusion period is expected to last 18 months. PHRC-K (grant PHRC-K22-084); Women’s Cancer Institute of Institut Curie (grant ANR-23-IAHU-0006). Citation Format: D. Loirat, F. C. Bidard, J. Grenier, T. L’Haridon, A. Kieffer, F. Dalenc, C. Goislard De Monsabert, F. Ricci, M. By, D. Bello Roufai, Y. Kirova, T. Roque, A. Savignoni, J. Y. Pierga. Cappa, a phase 2 study to evaluate capecitabine plus pembrolizumab as post-operative adjuvant therapy for triple-negative breast cancer with residual disease after neoadjuvant chemo-immunotherapy [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 PS5-07-16.