Background: T and A-DA showed antitumor activity in a PDX model of dedifferentiated-SFT (D-SFT) and a few cases of activity in advanced SFT pts have been reported. The efficacy of these agents in advanced typical- (T-)/ malignant- (M-)SFT is unclear. A phase 2 randomised (R) study was conducted within the Italian Sarcoma Group (ISG) to investigate the activity of T and A-DA in advanced T-, M- and D-SFT (Clin-Gov: NCT03023124). Methods: An Italian, multicentre, investigator-initiated prospective open-label, R, non-comparative, phase 2 trial was started in July 2017 involving 6 ISG sites, to evaluate the activity of front-line T (1,5-1,3 mg/sqm at investigator’s discretion, day 1 every 3 wks; arm A) vs A-DA (A 75 mg/sqm day 1 + DA 400 mg/sqm days 1,2 every 3 wks; arm B) in > 18 years-old pts with advanced SFT (T-SFT, M-SFT, D-SFT) until progression or limiting toxicity; in arm B, a maximum number of 6 cycles was foreseen, given the constrain of the maximum tolerated dose of A. Eligible pts had to show RECIST progression in the 6 mos prior to study entry. Centralized pathologic and radiologic review was performed. Pts were randomly assigned to Arm A or Arm B (1:1 ratio), with cross over in case of progression (PD) or unacceptable toxicity prior to the completion of the 6 cycles (arm B in case of randomization to arm A and vice versa). An interim analysis was pre-planned after reaching 10 evaluable pts in each arm, and at least 1 response in arm A was required to continue the study. Primary end-point was the overall response rate (ORR) by RECIST; secondary end-points ORR by Choi, progression-free survival (PFS), overall survival (OS). Results: Enrolment for the interim analysis was completed in September 2022. 30 pts were screened and 23 were enrolled (7 screening failure): T-SFT = 7, M-SFT = 14, D-SFT = 2. All pts were naïve; 3 pts are ongoing, 20 completed their treatment (12 = PD, 8 = other). All pts were evaluable for RECIST. No responses by RECIST were seen in each arm (ORR 0%), while stable disease (SD) and PD were 9 (45%) and 1 (5%) in arm A and 8 (40%) and 2 (10%) in arm B, respectively. At a 15.9-mo (I.Q. range 11.3-29.0) m-FU, m-PFS by RECIST was 9.2 (2.7-not assessable) mos in arm A and 8.0 (1.1-not assessable) mos in Arm B, with 29.6% progression-free pts at 1 year in arm A and 18.7% in arm B. Median OS was 34.3 (9.3-not assessable) mos in arm A, 31.5 (4.2-31.5) mos in arm B. Conclusions: No responses were seen neither to T nor to A-DA across all SFT subtypes; therefore, the study was closed to enrolment for T-SFT and M-SFT after the interim analysis. Noteworthy, both T and A-DA stabilised the disease in about 40% of previously progressive pts, and nearly 30% of pts treated with T were free from progression at 1 year. On the other hand, no conclusion can be drawn yet on the activity of T / A-DA in this SFT subtype, since D-SFT cases who entered the study were only 2 and the enrolment of D-SFT is still ongoing. Clinical trial information: NCT03023124.