11512 Background: Locally advanced DDLS is incurable with an overall survival of 11 – 20 mo with palliative therapies. Ideal imaging criteria for efficacy is currently undefined. Selinexor (S) is an oral, selective inhibitor of nuclear export that specifically blocks exportin 1, leading to the nuclear accumulation and reactivation of tumor suppressor proteins. S demonstrated anti-tumor activity against DDLS in preclinical studies and a Ph 1b study in patients (pts) with soft tissue sarcomas. Methods: Eligible pts had DDLS and progressive disease (PD) with ≥ 1 prior systemic therapy. Pts were randomized 1:1 to receive blinded S (60 mg) or placebo (P) twice weekly; 42 day cycle until PD or intolerability. Pts with PD on P may cross over to S. The primary endpoint was progression-free survival (PFS) by WHO criteria. Pre-specified analyses using RECIST v1.1 (R v1.1) was included. Results: Ph 2 enrollment is complete. 56 evaluable pts (33 M, 23 F) were randomized to S or P. Median age: 61 yrs and median prior treatments: 2 (1-9). Treatments for 51 pts were unblinded (24 S, 27 P). The main reason for ending blinded treatment was PD confirmed by Independent Central Radiological Review by WHO Criteria. Common AEs Grade 1/2 (S:P) were: nausea (85% : 31%), anorexia (62% : 14%), and fatigue (58% : 45%). Grade 3/4 AEs were: hyponatremia (15% : 0%), anemia (15% : 7%), and thrombocytopenia (12% : 0%). 12 pts on S had dose reductions due to AEs. There was no difference in median PFS by WHO. By R v1.1, median PFS on S: 5.6 mo; P: 1.8 mo, hazard ratio of 0.64 (p 0.21, not powered in Ph 2). (Table 1). Some pts ended treatment early with small changes in tumor burden due to PD by WHO criteria. Conclusions: R v1.1 may be better criteria than WHO to evaluate drug efficacy in DDLS. Improvement of PFS (R v1.1) is promising and supports continuation of the Ph 3 portion of S in DDLS. Clinical trial information: NCT02606461.Median PFS by R v1.1 and WHO criteria. Treatment Arm R v1.1 - PFS (mo) Hazard Ratio (95% CI) WHO - PFS (mo) Hazard Ratio (95% CI) Selinexor (N = 24) 5.6 0.64 (0.31, 1.32) p = 0.21 1.4 0.92 (0.52, 1.63) Placebo (N = 27) 1.8 1.4