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
1449 - Prognostic factors associated with pathological complete response in early breast cancer patients undergoing neoadjuvant chemotherapy. The importance of Ki-67 and molecular subtype.
Presenter: Bernardo Rapoport
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
4023 - The accuracy of sentinel lymph node biopsy following neoadjuvant chemotherapy in clinically node positive breast cancer patients: A single institution experience
Presenter: Narges Sistany Allahabadi
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
4707 - Index BRCA1/2 testing under a multidisciplinary program
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
3393 - BRCA1/BRCA2 germline mutations and chemotherapy-related hematological toxicity in breast cancer patients
Presenter: Alex Friedlaender
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
3175 - PALB2 germ-line mutations in Russian breast cancer patients: identification of recurrent alleles and analysis of phenotypic characteristics of the tumors
Presenter: Evgeny Imyanitov
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
3027 - Landscape of germline mutations in hereditary breast and ovarian cancer (HBOC) patients in Russia revealed by target panel sequencing
Presenter: Elena Shagimardanova
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
4963 - Lynch syndrome-associated hereditary mutations cause breast and ovarian cancer: results from Russian Heredetary Oncogenomics project
Presenter: Marat Gordiev
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
2916 - Impact of deleterious germline BRCA mutations, addition of taxanes and use of adjuvant endocrine therapy (ET) on anti-müllerian hormone (AMH) levels in early breast cancer (EBC) patients treated by adjuvant chemotherapy (CT)
Presenter: Nathalie OLYMPIOS
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
2400 - Germline mutation status and therapy response in patients with triple-negative breast cancer (TNBC): Results of the GeparOcto study
Presenter: Esther Pohl
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
1345 - BRCA1/BRCA2 Predictive Genetic Testing in an Irish Population: A Missed Opportunity
Presenter: David O Reilly
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