Phase III randomized study of adjuvant treatment with the ANTI-PD-L1 antibody avelumab for high-risk triple negative breast cancer patients: The A-BRAVE trial.

TPS598 Background: Chemotherapy represents, today, the only treatment option for triple negative breast cancer (TNBC) and still a considerable proportion of pts with primary TNBC experience disease relapse. The risk is particularly high in the presence of poor prognostic features, such as more advanced stage and, for pts treated with neoadjuvant chemotherapy, failure to achieve a pCR. Recent evidence suggest that immunotherapy can play a major role in TNBC pts. Methods: The A-BRAVE trial is an investigator-driven trial sponsored by the University of Padova (Dept. of Surgery, Oncology and Gastroenterology). This is a phase III, multicentric, randomized adjuvant study that compares 1 year of treatment with the anti PD-L1 avelumab vs observation for pts who completed treatment with radical intent for primary TNBC including surgery and chemotherapy. The study enrolls pts in two strata: -Stratum A: primary TNBC pts who completed surgery followed by adjuvant, defined according to one of the following stage categories: if pN2, any pT; if pN1, pT > 2 cm; if pN0, pT > 5 cm. -Stratum B: primary TNBC pts who completed neoadjuvant chemotherapy followed by surgery who did not achieve pCR. Pts who also received additional adjuvant chemotherapy for no more than 6 months are eligible in Stratum B, after the completion of the adjuvant chemotherapy. Pts are randomized (1:1, balanced for strata A and B) to receive Avelumab 10 mg/kg I.V. q2w for 1 year or to observation. The first and second co-primary endpoints are disease-free survival (DFS) in all pts and DFS in Stratum B pts. With a planned sample size of n = 474 pts the trial has 90% power to detect a HR = 0.60 for the first co-primary endpoint (n = 172 events required). Taking into account that the percentage of patients enrolled in the stratum B could range from 70 to 80%, there will be 70-79% power to detect a HR = 0.60 at alpha allocated in this patient subgroup (second co-primary endpoint). Secondary objectives include: DFS in PD-L1 positive pts, overall survival, safety, biomarkers. Tumor tissue, plasma samples and fecal samples are collected for biomarker analysis. The study is currently recruiting across 73 sites in Italy and UK. As of February 2020, n = 349 pts have been enrolled. EUDRACT 2016‐000189‐45. The authors present the A-BRAVE trial in progress on behalf of Italian and UK investigators. Clinical trial information: NCT02926196 .