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.
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, tolerability, identify maximum tolerated dose (MTD) or optimal dose/regimen, and assess pharmacokinetics, pharmacodynamics, 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; Currently enrolling 60 mg (escalation ongoing).
As of 4/27/18, 35 patients received SL-801 (median age 64 years [range: 39-76, 18 females, range: 1-11 prior therapies; 69% ≥3rd line). No dose limiting toxicity (DLT) has been identified, and a MTD has not been reached. Median follow-up was 1.4 months (range: 0.2-10.8). Dose-dependent increases in Cmax and AUC have been observed. The most frequent treatment-related grade 1-2 adverse events (TRAEs) were nausea (46%), vomiting (34%), fatigue (29%), decreased appetite (20%), and diarrhea (17%). 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). No grade 4 or 5 TRAEs reported. Eight patients (23%) had stable disease (SD) and remained on study for 3-15+ cycles. Six patients, with mucinous adenocarcinoma, GE junction, colon, neuroendocrine, basal cell, and breast cancer, had SD for ≥2.5 months; notably, the basal cell carcinoma patient had a SD response >9 months. Radiographic tumor shrinkage >10% noted in 3 patients.
SL-801 appears to be well tolerated in advanced solid tumor patients, and to date 23% of heavily pre-treated patients have achieved SD as best response. Enrollment and dose escalation continue.
Clinical trial identification
Legal entity responsible for the study
D. Qi: Consultant: Stemline Therapeutics. A. Olguin, J. Bullington, M. Sardone, V. Dunn, S. Shemesh, J. Chen, C. Brooks: Employment and stock ownership: Stemline Therapeutics. All other authors have declared no conflicts of interest.