Abstract 5422
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, 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).
Results
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.
Conclusions
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
NCT02667873.
Legal entity responsible for the study
Stemline Therapeutics.
Funding
Stemline Therapeutics.
Editorial Acknowledgement
Disclosure
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.
Resources from the same session
4596 - Neoadjuvant Trial of nab-paclitaxel and Atezolizumab (Atezo), a PD-L1 inhibitor, in patients (pts) with chemo-insensitive Triple Negative Breast Cancer (TNBC)
Presenter: Jennifer Litton
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
5349 - Prognostic implications of circulating tumor cells (CTCs) after neoadjuvant chemotherapy for triple negative breast cancer (TNBC)
Presenter: Carolyn Hall
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
2568 - A prediction model for pathological complete response after neoadjuvant chemotherapy of HER2-negative breast cancer patients
Presenter: Lothar Häberle
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
5413 - Evaluation of the MammaTyper® as a molecular predictor for pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) and outcome in patients with different breast cancer (BC) subtypes
Presenter: Peter A. Fasching
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
2260 - Impact of clinical, morphologic and molecular characteristics on response to neoadjuvant systemic therapy (NAST) in metaplastic breast cancer (MpBC)
Presenter: Clinton Yam
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
4722 - Evaluation of Human epidermal growth factor receptor 2 overexpression (HER2+) after administration of neoadjuvant treatment (NAT) and prognostic impact in breast cancer (BC)
Presenter: Duarte Machado
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
4307 - Complete response (CR) to anthracycline-based chemotherapy using magnetic resonance imaging (MRI) predicts high rates of pathologic complete response (pCR) for triple negative breast cancer (TNBC) patients treated preoperatively with anthracycline and taxane-based regimens
Presenter: Maria Marin Alcala
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
5018 - Immunomonitoring of triple negative breast cancer patients undergoing neoadjuvant therapy (GBG89, Geparnuevo trial)
Presenter: Barbara Seliger
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3203 - Impact of breast cancer subtype on survival after lumpectomy versus mastectomy for early stage invasive breast cancer
Presenter: YU-CHEN Tsai
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
4887 - Survival Outcomes of Dose Dense Neoadjuvant and Adjuvant Chemotherapy in Triple-Negative Breast Cancer Patients – Indian Scenario
Presenter: TANVI Sood
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract