Background: Angiosarcoma (AS) is an aggressive soft tissue sarcoma (STS) of endothelial origin with reported median OS of 8-12 months. Pazopanib (P) is approved for treatment of advanced STS refractory to an anthracycline. In a retrospective study of 40 AS patients treated with single agent P, median PFS was 3.1 months and median OS 9.9 months with a low response rate and no complete responses. Endoglin is an essential angiogenic receptor expressed on AS that is upregulated following VEGF inhibition. TRC105, an endoglin antibody, combined with P achieved durable complete responses in two of 18 AS patients, with median PFS of 7.8 months in chemotherapy-refractory and P-naïve patients enrolled in a Phase 1/2 trial. The TAPPAS Phase 3 trial was initiated following protocol assistance from the EMA and Special Protocol Assessment from the FDA. Methods: TAPPAS (NCT02979899) is a randomized multicenter study of TRC105/P vs P alone actively enrolling cutaneous and non-cutaneous AS patients at > 25 sites in the United States and Europe, and incorporates an adaptive enrichment design. Key inclusion criteria: 0, 1 or 2 prior lines of therapy, ECOG ≤ 1. Primary endpoint is PFS. Secondary endpoints include ORR and OS. The initial sample size of 124 patients, followed until 95 PFS events, provides more than 80% power to detect a hazard ratio of 0.55. At the time of interim analysis, projected to occur upon the occurrence of 40 events in approximately 70 patients, the trial will be classified as belonging to either the favorable, promising, enrichment or unfavorable zones, based on conditional power. Sample size and PFS events will be unchanged in the favorable and unfavorable zones, and will be increased to a total of 200 patients followed for 170 events in the promising zone. The trial will enroll a total of 135 patients with cutaneous disease followed for 110 events in the enrichment zone. An independent Data Monitoring Committee will follow the trial for safety and futility and recommend sample size or population adaptation. The adaptive design permits enrollment of fewer and more responsive patients over a shorter time compared to a fixed sample size design, while preserving type-1 error. Clinical trial information: NCT02979899