Background: SXR is an orally administered potent XPO1 inhibitor that forces nuclear retention and activation of multiple tumor suppressor proteins resulting in tumor cell death. SXR was evaluated in Asian pts with advanced cancer to assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDn) and efficacy. Methods: SXR dose escalation was initiated in a 3+3 design on a twice weekly continuous 28 day cycle, schedule 1 (S1), but stopped due to persistent drug-related adverse events (AEs). Two further schedules were explored: S2, once weekly continuously every 28 days, and S3, twice weekly for 2 weeks of a 21 day cycle. Serial tumor biopsies were performed pre- and 6-8 weeks post SXR. RECIST/ Cheson lymphoma criteria for response was evaluated every 2 cycles. Results: 18 pts (median age 61 yrs; ECOG 0-1) received escalating doses of SXR across 3 schedules. In S1 no dose-limiting toxicity (DLT) occurred at expanded dose-level (DL) 1 (40mg/m², 6pts), but was stopped due to persistent ≥ G2 AEs (fatigue [50%], hyponatremia [50%], anorexia [17%]) post cycle 1. In S2, at DL1 (50mg/m², 3pts) and DL2 (60mg/m², 3pts), G1/2 AEs were hyponatremia (67%), nausea (33%), fatigue (50%) and anorexia (50%) with no ≥ G3 AEs. In S3, at DL1 (40mg/m², 3 pts) and DL2 (50mg/m², 3 pts); AEs were hyponatremia G1/2 (50%) and ≥ G3 (50%), nausea G1/2 (33%) and ≥ G3 (17%), fatigue G1/2 (67%) and ≥ G3 (33%), anorexia G1/2 (67%). No DLTs occurred in S2/S3. PK analysis demonstrated SXR exposure with no accumulation and comparable half-life and clearance when compared with non-Asian pts. At 40mg/m², AUC_0-inf (5,222 ng*h/mL) was comparable to the anti-tumor exposure observed in mice and dogs. Mean T_max = 2hrs and T_1/2 = 5.7 hrs. Reduced cellularity and proliferation with increased fibrosis and apoptosis was seen in tumors post-SXR administration. Of 13 evaluable pts, best responses were PR in 2pts with refractory diffuse-large B-cell lymphoma, SD in 8 pts (colorectal [n = 2], pancreas, squamous cell tongue, non-small cell lung, ovarian and hepatocellular carcinoma [n = 2]), and PD in 3pts. Conclusions: Dose-escalation of SXR is ongoing on S2 and S3 with more G3 AEs seen in S3. Promising antitumor activity was observed. Clinical trial information: NCT02078349