Background: Preclinical studies have shown that cell lines and murine models of TNBC phenotype are more sensitive to PARP1 inhibitors. This evidence provides strong rationale for developing a new therapeutic approach to TNBC based on targeting the DNA-repair defects via PARP inhibition. Methods: The purpose of this study was to report the Maximal Tolerated Dose (MTD) of Olaparib (O) administered concurrently with locoregional RT and evaluate the Dose-Limiting Toxicity (DLT). Results: Twenty-four pts with performance status 0-1 were enrolled between 09/2017 and 11/2019. Of them, 21 underwent adjuvant RT-O because poor response to NAC, and 3 received preoperative RT+O because of progression after NAC. The patients’ profile is given in table. All patients received full course RT-O, as following: 4 pts at dose 50mg bid; 8 at 100x2; 7 at 150x2, and 5 at 200x2. No DLT was observed. Two pts (8.7%) experienced acute grade 3 dermatitis no grade 4 toxicities related to the RT were observed. The O-related toxicity was acceptable with mostly grade 1-2 symptoms. The only grade 3-4 hematological toxicity was lymphopenia in 11 cases. Conclusions: Dose of O was escalated to the target dose of 200 mgx2, without DLT. Further follow up is needed to evaluate the late toxicities. Clinical trial information: NCT03109080.