Background: SL-801 is a novel, oral, small molecule reversible inhibitor of Exportin-1 (XPO-1), a critical nuclear export protein overexpressed in many cancers. SL-801 has demonstrated potent in vitro and in vivo anti-tumor activity against a broad range of hematologic and solid cancers. SL-801’s reversible inhibition of XPO-1 may translate to selective activity and potential safety benefits. Interim results from the dose-escalation study are reported. Methods: STML-801-0115 is a first-in-human, multicenter Phase 1 3x3 dose escalation study in patients with localized unresectable, or metastatic solid tumors resistant to or relapsed following standard therapy. Objectives are to evaluate safety and tolerability, identify maximum tolerated dose (MTD) or optimal dose/regimen for further evaluation, and assess pharmacokinetics and preliminary anti-tumor activity. SL-801 is orally administered on days 1-4 and 8-11 of a 21-day cycle. Starting dose was 5 mg and is currently 55 mg (escalation ongoing). Results: As of 1/6/18, 31 pretreated patients (range: 1-11 prior therapies; 71% ≥3rd line) received SL-801 (16 females, median age 63 years [range: 39-76]). No dose limiting toxicity (DLT) has been identified, and a MTD has not been reached. Median follow-up is 1.4 months (range: 0.2-8.5). Dose-dependent increases in C_max and AUC have been observed. The most frequent treatment-related grade 1-2 adverse events (TRAEs) were nausea (45%), vomiting (32%), diarrhea (19%), fatigue (26%) and decreased appetite (19%). Grade 3 TRAEs included nausea (n = 3; 40, 45, 50 mg), vomiting (n = 1; 45 mg), diarrhea (n = 2; 10, 50 mg), acute renal injury (n = 1; 30 mg), and neutropenia (n = 1; 10 mg). There were no grade 4 or 5 TRAEs. Nine patients had stable disease (SD) for 3-12+ cycles. Five patients, with GE junction, colon, neuroendocrine, basal cell, and breast cancer, had SD ≥4 months. Radiographic tumor shrinkage > 10% was noted in 3 patients. Conclusions: SL-801 appears to be well tolerated in advanced solid tumor patients, and 29% of patients achieved SD as best reponse. Enrollment and dose escalation continue in an effort to identify an optimal dose and regimen. Clinical trial information: NCT02667873