Background: Pazopanib, a multitarget TKI, has been approved as second or later line treatment for advanced non-adipocytic soft-tissue sarcoma. This open-label, phase II clinical trial was designed to assess the activity of pazopanib in patients with advanced LPS in two independent cohorts: well-differentiated/ dedifferentiated (WD/DD cohort A) and myxoid/round-cell (M/RC cohort B) LPS. Methods: Pts ≥ 18 years old, ECOG 0-1, with high- or intermediate-grade LPS (excluding pleomorphic) with locally advanced or metastatic measurable disease (per RECIST 1.1) were eligible. Pts had to be unsuitable or had failed at least one line of systemic therapy but no more than 3 lines. Central pathologic review was performed before study entry to confirm diagnosis and assign the patient into one of the two cohorts. All patients received pazopanib 800 mg once daily until tumor progression, unacceptable toxicity, death, or pt’s withdrawal. The primary study endpoint was Progression-free survival (PFS) rate assessed 12 weeks (w) after start of treatment. A Simon two-stage design was applied (P1 = 40%; P0 = 20%; alpha = .1) for each cohort. Patients had CT scan assessments at baseline, w6, w12 and every 8w thereafter. Local and central radiological review was performed. Results: 52 pts were enrolled at 12 centers in Spain and Germany between January 2013 and July 2015. 28 pts (53.8%) were male and median age was 58.3 years. Cohort B was closed after 15 pts because of lack of activity, while cohort A was completed up to 37 pts. According to local assessment PFS at 12w was 43.2% for cohort A and 13.3% for cohort B. Median PFS and overall survival was 3.5 months (m) and 16.4 m for cohort A and 1.99 m and 22.33 m for cohort B, respectively. No objective response was observed. Adverse events for pazopanib were as expected. Data on central radiologic review and growth modulation index will be presented. Conclusions: This study corroborates that pazopanib is well tolerated and is potentially active in the treatment of WD/DD LPS as it is in other sarcoma subtypes, but not in M/RC LPS. Clinical trial information: NCT01692496