Background: SGC of head and neck (SGCHN) are rare tumors including adenoid cystic carcinoma (ACC) and non-ACC, with no standard systemic treatment for R/M patients (pts). Pazopanib (Pb) is an oral small molecule inhibitor of VEGFR, PDGFR and KIT. We conducted a multicenter single arm phase II study to assess the antitumor activity of Pb in ACC and non-ACC SGCHN. Methods: Pts with confirmed progressive R/M SGCHN received Pb 800 mg daily until progression (PD). Response was assessed every 12 weeks (RECIST). Primary endpoint was the 6-mo PFS rate. Secondary endpoints included response rate (CR/PR), overall survival, toxicity. For ACC pts, the trial was designed with inacceptable and promising 6-mo PFS rates of 20% and 40%, requiring 43 evaluable pts (alpha error = 0.07, power = 0.93). For non-ACC pts, trial was exploratory on 20 pts. A study of tumor growth rates is ongoing. Results: From 2013 to 2015, 72 pts were enrolled: 49 ACC and 20 non-ACC (3 ineligible excluded) including 11 adenocarcinoma (ADK), M:F = 32:37, median age 59 yrs (range 27-84), PS 0-1 = 42:27, prior radiation: 64 (93%), prior systemic therapy: 40 (58%). The most frequent adverse events (AE) (% of pts) were fatigue (81%), nausea (59%), diarrhea (54%), high blood pressure (BP) (43%), and anorexia (33%). 31/69 pts experienced grade 3 AE, primarily fatigue and high BP. Two grade 4 AE (cerebrovascular stroke, hepatitis) and 1 death (infection) were possibly related to treatment. Median FU was 13 mo. Among 46 ACC pts evaluable for efficacy (3 non progressive excluded), best response was 1 (2%) PR, 35 (76%) SD, 10 (22%) PD. 4 pts withdrew, 7 discontinued therapy due to AE. 6-mo PFS rate was 43% (95%CI = 29;57) with 20 pts without PD at 6 mo, median PFS was 5.9 mo. Median OS was 16.6 mo with 1 year OS = 64.8%. For 18 non-ACC pts evaluable for efficacy (2 non progressive excluded), best response was 1 PR (6%), 13 SD (72%), 4 PD (22%). 4 pts discontinued therapy due to AE. 6-mo PFS rate was 50% (95%CI = 29;71), median PFS was 6.7 mo (8 mo for ADK), median OS was not reached with 1 year OS = 75%. Conclusions: There were no new safety signals, tolerance was as expected. PACSA is positive with a 6-mo PFS rate > 40% observed in ACC and non-ACC pts. Pb is promising and deserves further studies. Clinical trial information: NCT02393820