Background: Selinexor is a first-in-class SINE compound with single-agent activity in STS. We undertook this study to determine the safety, tolerability and efficacy of selinexor when combined with doxorubicin in pts with locally advanced or metastatic STS. Methods: This phase 1b study was conducted using a modified toxicity probability index (mTPI) design. Patients with locally advanced or metastatic STS received selinexor at two dose levels (60 or 80mg weekly PO) plus doxorubicin (75mg/m² IV q21 days, max 6 cycles). Pts with stable disease or better (per RECIST 1.1 criteria) after 6 cycles of combination treatment received selinexor monotherapy until disease progression or unacceptable toxicity. Disease assessments were made with standard imaging after every 2 cycles. Limited pharmacokinetic (PK) data was collected for the first 3 pts at each dose level. Results: 13 pts (11F/2M, ECOG 0/1: 5/8, median age 63 years [range 51-73]) were enrolled. Disease subtypes included leiomyosarcoma (n = 6), undifferentiated pleomorphic sarcoma (n = 2; UPS), liposarcoma (n = 2) and other sarcomas (n = 3). Three pts at 60mg selinexor and 10 pts at 80mg selinexor have been treated. The most common G3 drug related adverse events (AEs) were hematological, including neutropenia n = 6 (46%), anemia n = 3 (23%). There were two dose-limiting toxicities (febrile neutropenia and unresolved fatigue lasting more than 7 days), both at the 80mg dose level. Of the 13 evaluable pts (median follow-up of 15 weeks [range 5-31]), partial response was seen in 3 pts (23%, n = 1 for UPS, malignant peripheral nerve sheath tumor and myxofibrosarcoma) and stable disease was seen in 7 (54%). PK analysis of selinexor did not demonstrate changes compared to single agent profile. Conclusions: Our initial data demonstrate that the combination of selinexor and doxorubicin appears to be tolerable and safe. There was no exposure changes oberserved for selinexor in this combination regimen. Updated toxicity, safety and efficacy data will be presented at the meeting. Clinical trial information: NCT03042819