Background: We reported on a phase I trial showing 54% confirmed partial response (PR) with carb + vel. Here we describe single agent vel activity and, upon progression, the feasibility and efficacy of continuing administration of vel + carb. Methods: Pts with MBC with BRCA1 or 2 mutations, an ECOG performance status of ≤ 2, and measurable disease were eligible. Prior PARP-inhibitor therapy (Rx) , platinum Rx for MBC, or central nervous system metastasis requiring Rx were exclusions. Vel was administered orally at 400 mg twice daily (BID). Cohorts (BRCA1 and BRCA2) were studied independently: 2 or more PRs to vel out of 10 pts were required to proceed to accrual of 22 pts per cohort. Upon progression, carb (AUC of 5) iv every 21 days, and vel 150 mg orally BID were prescribed. Results: Between 10/2012 and 1/2014, 44 pts enrolled (41 treated) carrying BRCA1 (N=21) or BRCA2 (N=20) mutations. The median age was 43-years (range; 28-68); 50% of pts had hormone receptor + BC. Pts received 3 prior chemo-regimens (0-7). The current PR rate in pts with at least 4 cycles of follow-up is 2/12 (17%) for BRCA1 and 3/13 (23%) for BRCA2. Three pts withdrew from treatment during the first cycle of vel due to grade 2 seizure (1), grade 3 thrombocytopenia (PLT [1]), grade 2 PLT and neutropenia (1). Time to failure (TTF) on vel is 2.0 months (0-10.5+), and 5.1 months (0.9-10.3+) for the two cohorts (BRCA1, BRCA2, respectively). Twenty pts are still on vel (8 BRCA1, 12 BRCA2). Of the 10 pts to proceed to vel + carb so far, 1 PR in a BRCA1 pt was observed. Conclusions: Vel is active when given at 400 mg BID daily. Further trials are indicated to assess its benefit whether in combination or as a single agent in both BRCA1 and BRCA2-associated BC. Clinical trial information: NCT01149083.