Trial for Treatment of High Risk BC With Two Sequences of Neoadjuvant Chemotherapy With Pembrolizumab

This is a randomized, open-label, pilot study to evaluate the existence of a differential tumor immunomodulatory profile of neoadjuvant pembrolizumab in combination with paclitaxel and carboplatin vs pembrolizumab in combination with EC/AC in patients with triple negative, tumor infiltrating lymphocytes (TILs) enriched, early breast cancer to allow the optimization of future de-escalation strategies. There will be crossover between treatment arms when moving from the neoadjuvant to adjuvant treatment period for completion of standard chemotherapy plus pembrolizumab. The chemotherapy regimen included in this study is built upon previous studies of pembrolizumab plus chemotherapy. The synergistic effect of different chemotherapy backbone and pembrolizumab will be studied as part of a 2-arm study: Arm 1: (KXCb - PA\[E\]C): Pembrolizumab (K) every 3 weeks (Q3W) + paclitaxel (X) + carboplatin (Cb) once weekly (QW) for 4 cycles in the neoadjuvant setting followed by pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles followed by pembrolizumab every 6 weeks for 5 cycles (total of 1 year of pembrolizumab) in the adjuvant setting. Arm 2: (KPA\[E\]C - KXCb): Pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles in the neoadjuvant setting followed by pembrolizumab (K) every 3 weeks (Q3W) + paclitaxel (X) + carboplatin (Cb) once weekly (QW) for 4 cycles followed by pembrolizumab every 6 weeks for 5 cycles (total of 1 year of pembrolizumab) in the adjuvant setting. In case of clinical evidence of non-pCR, i.e., biopsy proven residual disease after the neoadjuvant phase, patients can proceed to the crossover part of the adjuvant phase before surgery (i.e., 4 cycles of chemotherapy plus pembrolizumab) receiving the remaining administrations of pembrolizumab after surgery.