We are international
Donate
TEXT SIZE   


ASCO 2014: Phase 1-2 open-label, multiple-dose, dose-escalation study to evaluate the safety and tolerability of intravenous infusion of SNS01-T, a first-in-class modulator of eukaryotic translation initiation factor 5A (eIF5A) in patients (pts) with relapsed or refractory B-cell malignancies

David Siegel, MD
John Theurer Cancer Center
Hackesack, New Jersey, USA

06.13.14

Abstract No: TPS8616

Background: eIF5A has been implicated in the regulation of cell proliferation, apoptosis, and inflammation. It is the only known protein to be modified by hypusination, and is highly conserved across species and is active in plants and animals. Hypusinated eIF5A, the predominant form in normal and cancer cells, is involved in cell survival and inflammatory pathway activation. siRNAs targeting eIF5A inhibit NF-kB activation and reduce pro-inflammatory cytokine production. Accumulation of the unhypusinated lysine form of eIF5A is associated with apoptosis. Mutants of eIF5A that cannot be hypusinated (e.g. eIF5AK50R) are pro-apoptotic in vitro and have anti-tumoral activity in vivo in multiple cancer types including melanoma and lung cancer. SNS01-T is a novel therapeutic with a dual mechanism of eIF5A modulation: inducing cell death via siRNA-mediated inhibition of hypusinated eIF5A while simultaneously causing over-expression of pro-apoptotic eIF5AK50R via a DNA plasmid with a B-cell promoter to induce tumor cell death. SNS01-T significantly inhibited tumor growth and increased survival in mouse models of myeloma (MM), mantle cell and diffuse large B-cell lymphoma.

Methods: This is an open label, phase 1-2 dose escalation study in pts with refractory B-cell cancers. The study has 4 dose cohorts: 0.0125, 0.05, 0.2 and 0.375 mg/kg twice weekly IV for 6 weeks. Main inclusion criteria are: MM per IMWG criteria or lymphomas or plasma cell leukemia with histologic confirmation; measurable disease; relapsed or refractory disease after ≥2 prior regimens; life expectancy ≥3 months; not eligible for any other standard therapy known to extend life expectancy. Primary endpoints are safety and tolerability of SNS01-T. Secondary endpoints include pharmacokinetics, tumor response (M protein, % plasma cells, radiologic response) and time to relapse or progression. To date, 15 patients have been included in the study. Enrolment (n=6) at the highest dose cohort has commenced (1 pt enrolled). Cohort 4 is expected to be completed in 1H2014

Clinical trial information: NCT01435720.  

Author(s): Michael Craig, William Bensinger, David Samuel DiCapua Siegel, Frits Van Rhee, Nicolas Novitzky, Andrew Mcdonald, Martin Gutierrez, Edward N. Libby, John Thompson, Alice Susannah Bexon, Charles Barranco, Catherine Taylor, Richard Dondero, Leslie J. Browne, Michael R. Kurman, John Anthony Lust; West Virginia University, Morgantown, WV; Fred Hutchinson Cancer Research Center, Seattle, WA; John Theurer Cancer Center, Hackensack, NJ; Myeloma Institute for Research and Therapy, Little Rock, AR; University of Cape Town - Medcl School, Cape Town, South Africa; Pretoria East Hospital, Pretoria, South Africa; University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Biology, University of Waterloo, Waterloo, ON, Canada; Senesco Technologies, Inc., Bridgewater, NJ; University of Waterloo, Waterloo, ON, Canada; Senesco Technologies, Inc., New Brunswick, NJ; Kyowa Hakko Kirin Pharma, Inc., Upper Saddle River, NJ; Mayo Clinic, Rochester, MN

 


 related articles
ASCO 2014: Overview ...
ASCO 2014: Remission...
ASCO 2014: Continuou...
ASCO 2014: DETERMINA...
ASCO 2014: Continuou...
ASCO 2014: MM-005: P...
ASCO 2014: A phase I...
ASCO 2014: E1A06: A ...
ASCO 2014: Optimizin...
ASCO 2014: Pomalidom...
ASCO 2014: MM-014: A...
ASCO 2014: A phase I...
ASCO 2014: A phase 1...
ASCO 2014: Safety an...
ASCO 2014: Continuou...
ASCO 2014: MM-005: P...
ASCO 2014: DETERMINA...
ASCO 2014: Treatment...
ASCO 2014: A phase I...
ASCO 2014: SWOG 1211...
ASCO 2014: Results o...
ASCO 2014: Optimizin...
ASCO 2014: Survival ...
ASCO 2014: Prevalenc...
ASCO 2014: Safety an...
ASCO 2014: Dose-depe...
ASCO 2014: A phase I...
ASCO 2014: A phase I...
ASCO 2014: Panorama ...
ASCO 2014: Prelimina...
ASCO 2014: ECOG mult...
ASCO 2014: Free ligh...
ASCO 2014: Phase 1-2...
ASCO 2014: Prevalenc...
ASCO 2014: SWOG 1211...
ASCO 2014: The Impac...
ASCO 2014: A phase I...
Myeloma Minute
...


ASCO 2014: Overview of the ASCO 2014 Annual Meeting
ASCO 2014: Remission of Disseminated Cancer After Systemic Oncolytic Virotherapy (n.b., using modified measles vaccine)
ASCO 2014: Continuous treatment (CT) versus fixed duration of therapy (FDT) in newly diagnosed myeloma patients: PFS1, PFS2, OS endpoints.
ASCO 2014: DETERMINATION trial: A phase III multi-center study examining the timing of stem cell transplant for multiple myeloma
ASCO 2014: Continuous lenalidomide (LEN) therapy versus observation following nonimmunomodulatory compound-based induction therapy in newly diagnosed multiple myeloma (NDMM): MM-027 trial
ASCO 2014: MM-005: Phase 1 trial of pomalidomide (POM), bortezomib (BORT), and low-dose dexamethasone (LoDEX [PVD]) in lenalidomide (LEN)-refractory and proteasome inhibitor (PI)-exposed myeloma
ASCO 2014: A phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone (QUAD) in relapsed and/or refractory multiple myeloma (MM)
ASCO 2014: E1A06: A phase III trial comparing melphalan, prednisone, and thalidomide (MPT) versus melphalan, prednisone, and lenalidomide (MPR) in newly diagnosed multiple myeloma (MM)
ASCO 2014: Optimizing induction and pretransplant consolidation for myeloma: Results of Myeloma XI, a phase III trial comparing different IMiDs
ASCO 2014: Pomalidomide plus low-dose dexamethasone (POM plus LoDEX) versus high-dose dexamethasone (HiDEX) for relapsed or refractory multiple myeloma (RRMM): Overall survival (OS) results of MM-003 after adjustment for crossover
ASCO 2014: MM-014: A phase 2 trial evaluating efficacy, safety, and biomarkers of pomalidomide plus low-dose dexamethasone (POM + LoDEX) in relapsed/refractory multiple myeloma (RRMM) following second-line lenalidomide plus dexamethasone (LEN + DEX)
ASCO 2014: A phase Ib dose escalation trial of SAR650984 (Anti-CD-38 mAb) in combination with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma
ASCO 2014: A phase 1 (Ph1) trial of MK-3475 combined with lenalidomide (Len) and low-dose dexamethasone (Dex) in patients (pts) with relapsed/refractory multiple myeloma (RRMM)
ASCO 2014: Safety and efficacy of daratumumab with lenalidomide and dexamethasone in relapsed or relapsed, refractory multiple myeloma
ASCO 2014: Continuous treatment (CT) versus fixed duration of therapy (FDT) in newly diagnosed myeloma patients: PFS1, PFS2, OS endpoints.
ASCO 2014: MM-005: Phase 1 trial of pomalidomide (POM), bortezomib (BORT), and low-dose dexamethasone (LoDEX [PVD]) in lenalidomide (LEN)-refractory and proteasome inhibitor (PI)-exposed myeloma
ASCO 2014: DETERMINATION trial: A phase III multi-center study examining the timing of stem cell transplant for multiple myeloma
ASCO 2014: Treatment of relapsed/refractory multiple myeloma with weekly cyclophosphamide plus bortezomib plus prednisone or dexamethasone (CyBor-P/D): Updated experience at Princess Margaret Cancer Centre (PMCC)
ASCO 2014: A phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone (QUAD) in relapsed and/or refractory multiple myeloma (MM)
ASCO 2014: SWOG 1211: A randomized phase I/II study of optimal induction therapy for newly diagnosed high-risk multiple myeloma (HRMM)
ASCO 2014: Results of the dose-escalation portion of a phase 1/2 study (CHAMPION-1) investigating weekly carfilzomib in combination with dexamethasone for patients with relapsed or refractory multiple myeloma
ASCO 2014: Optimizing induction and pretransplant consolidation for myeloma: Results of Myeloma XI, a phase III trial comparing different IMiDs
ASCO 2014: Survival benefit and cost of autologous hematopoietic stem cell transplantation (Auto HSCT) in elderly patients with multiple myeloma (MM) using the SEER-Medicare database
ASCO 2014: Prevalence of high symptom burden and its impact on functioning and quality of life in patients with multiple myeloma 3-9 months following autologous transplant
ASCO 2014: Safety and efficacy of daratumumab with lenalidomide and dexamethasone in relapsed or relapsed, refractory multiple myeloma
ASCO 2014: Dose-dependent efficacy of daratumumab (DARA) as monotherapy in patients with relapsed or refractory multiple myeloma (RR MM)
ASCO 2014: A phase I trial of SAR650984, a CD38 monoclonal antibody, in relapsed or refractory multiple myeloma
ASCO 2014: A phase Ib dose escalation trial of SAR650984 (Anti-CD-38 mAb) in combination with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma
ASCO 2014: Panorama 1: A randomized, double-blind, phase 3 study of panobinostat or placebo plus bortezomib and dexamethasone in relapsed or relapsed and refractory multiple myeloma
ASCO 2014: Preliminary safety and efficacy of TH-302, an investigational hypoxia-targeted drug, and dexamethasone (dex) in patients (pts) with relapsed/refractory multiple myeloma (RR MM)
ASCO 2014: ECOG multiple myeloma (MM) clinical trial (CT) accrual performance evaluation utilizing the NCI–Trial Complexity and Elements Scoring (NCI-TCES) and the NCI Myeloma Steering Committee Accrual Working Group (NCI MYSC AWG) scoring models
ASCO 2014: Free light chain assay and cytogenetic abnormalities for identification of high-risk smoldering myeloma
ASCO 2014: Phase 1-2 open-label, multiple-dose, dose-escalation study to evaluate the safety and tolerability of intravenous infusion of SNS01-T, a first-in-class modulator of eukaryotic translation initiation factor 5A (eIF5A) in patients (pts) with relapsed or refractory B-cell malignancies
ASCO 2014: Prevalence of high symptom burden and its impact on functioning and quality of life in patients with multiple myeloma 3-9 months following autologous transplant
ASCO 2014: SWOG 1211: A randomized phase I/II study of optimal induction therapy for newly diagnosed high-risk multiple myeloma (HRMM)
ASCO 2014: The Impact of Race and Socio-Economic Status on Survival in Multiple Myeloma
ASCO 2014: A phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone (QUAD) in relapsed and/or refractory multiple myeloma (MM)
Myeloma Minute
March 5, 2015


You might also be interested in:

Commentaries
ASCO 2014: Overview of the ASCO 2014 Annual Meeting

Dr. Paul Richardson
Dana-Farber Cancer Institute
Boston, Massachusetts, USA


ASCO 2014: Remission of Disseminated Cancer After Systemic Oncolytic Virotherapy (n.b., using modified measles vaccine)

Angela Dispenzieri, MD
Mayo Clinic
Rochester, Minnesota, USA


Immunomulatory Agents
ASCO 2014: Continuous treatment (CT) versus fixed duration of therapy (FDT) in newly diagnosed myeloma patients: PFS1, PFS2, OS endpoints.

Antonio Palumbo, MD
University of Torino
Torino Italy


ASCO 2014: DETERMINATION trial: A phase III multi-center study examining the timing of stem cell transplant for multiple myeloma

Paul Richardson, MD
Dana-Farber Cancer Institute
Boston, Massachusetts, USA


ASCO 2014: Continuous lenalidomide (LEN) therapy versus observation following nonimmunomodulatory compound-based induction therapy in newly diagnosed multiple myeloma (NDMM): MM-027 trial

Saad Z. Usmani, MD
Levine Cancer Institute - Morehead
Charlotte, North Carolina, USA


ASCO 2014: MM-005: Phase 1 trial of pomalidomide (POM), bortezomib (BORT), and low-dose dexamethasone (LoDEX [PVD]) in lenalidomide (LEN)-refractory and proteasome inhibitor (PI)-exposed myeloma

Paul Richardson, MD
Dana-Farber Cancer Institute
Boston, Massachusetts, USA


ASCO 2014: A phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone (QUAD) in relapsed and/or refractory multiple myeloma (MM)

David Siegel, MD
John Theurer Cancer Center
Hackensack, New Jersey, USA


ASCO 2014: E1A06: A phase III trial comparing melphalan, prednisone, and thalidomide (MPT) versus melphalan, prednisone, and lenalidomide (MPR) in newly diagnosed multiple myeloma (MM)

Keith K. Stewart, MB ChB
Mayo Clinic
Scottsdale, Arizona, USA


ASCO 2014: Optimizing induction and pretransplant consolidation for myeloma: Results of Myeloma XI, a phase III trial comparing different IMiDs

Charlotte Pawlyn, MD
Institute of Cancer Research
Sutton, United Kingdom


ASCO 2014: Pomalidomide plus low-dose dexamethasone (POM plus LoDEX) versus high-dose dexamethasone (HiDEX) for relapsed or refractory multiple myeloma (RRMM): Overall survival (OS) results of MM-003 after adjustment for crossover

Charlotte Pawlyn, MD
Institute of Cancer Research
Sutton, United Kingdom


ASCO 2014: MM-014: A phase 2 trial evaluating efficacy, safety, and biomarkers of pomalidomide plus low-dose dexamethasone (POM + LoDEX) in relapsed/refractory multiple myeloma (RRMM) following second-line lenalidomide plus dexamethasone (LEN + DEX)

David Siegel, MD
John Theurer Cancer Center
Hackensack, New Jersey, USA


ASCO 2014: A phase Ib dose escalation trial of SAR650984 (Anti-CD-38 mAb) in combination with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma

Thomas G. Martin, MD
University of California SF
San Francisco, California, USA


ASCO 2014: A phase 1 (Ph1) trial of MK-3475 combined with lenalidomide (Len) and low-dose dexamethasone (Dex) in patients (pts) with relapsed/refractory multiple myeloma (RRMM)

David Siegel, MD
John Theurer Cancer Center
Hackensack, New Jersey, USA


ASCO 2014: Safety and efficacy of daratumumab with lenalidomide and dexamethasone in relapsed or relapsed, refractory multiple myeloma

Torben Plesner, MD
Department of Hematology, Vejle Hospital
Vejle, Denmark


Proteosome Inhibitors
ASCO 2014: Continuous treatment (CT) versus fixed duration of therapy (FDT) in newly diagnosed myeloma patients: PFS1, PFS2, OS endpoints.

Antonio Palumbo, MD
University of Torino
Torino Italy


ASCO 2014: MM-005: Phase 1 trial of pomalidomide (POM), bortezomib (BORT), and low-dose dexamethasone (LoDEX [PVD]) in lenalidomide (LEN)-refractory and proteasome inhibitor (PI)-exposed myeloma

Paul Richardson, MD
Dana-Farber Cancer Institute
Boston, Massachusetts, USA


ASCO 2014: DETERMINATION trial: A phase III multi-center study examining the timing of stem cell transplant for multiple myeloma

Paul Richardson, MD
Dana-Farber Cancer Institute
Boston, Massachusetts, USA


ASCO 2014: Treatment of relapsed/refractory multiple myeloma with weekly cyclophosphamide plus bortezomib plus prednisone or dexamethasone (CyBor-P/D): Updated experience at Princess Margaret Cancer Centre (PMCC)

Donna Reece, MD
Princess Margaret Cancer Centre
Toronto, Ontario, Canada


ASCO 2014: A phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone (QUAD) in relapsed and/or refractory multiple myeloma (MM)

David Siegel, MD
John Theurer Cancer Center
Hackensack, New Jersey, USA


ASCO 2014: SWOG 1211: A randomized phase I/II study of optimal induction therapy for newly diagnosed high-risk multiple myeloma (HRMM)

Saad Z. Usmani, MD
Levine Cancer Institute - Morehead
Charlotte, North Carolina, USA


ASCO 2014: Results of the dose-escalation portion of a phase 1/2 study (CHAMPION-1) investigating weekly carfilzomib in combination with dexamethasone for patients with relapsed or refractory multiple myeloma

James R. Berenson, MD
Institute for Myeloma & Bone Cancer Research
West Hollywood, California, USA


Stem Cell Transplant
ASCO 2014: Optimizing induction and pretransplant consolidation for myeloma: Results of Myeloma XI, a phase III trial comparing different IMiDs

Charlotte Pawlyn, MD
Institute of Cancer Research
Sutton, United Kingdom


ASCO 2014: Survival benefit and cost of autologous hematopoietic stem cell transplantation (Auto HSCT) in elderly patients with multiple myeloma (MM) using the SEER-Medicare database

Gunjan L. Shah, MD
Tufts Medical Center Oncology
Boston Massachusetts, USA


ASCO 2014: Prevalence of high symptom burden and its impact on functioning and quality of life in patients with multiple myeloma 3-9 months following autologous transplant

Xin Shelley Wang, MD
MD Anderson Cancer Center
Houston, Texas, USA


Anti-CD38 Monoclonal Antibodies
ASCO 2014: Safety and efficacy of daratumumab with lenalidomide and dexamethasone in relapsed or relapsed, refractory multiple myeloma

Torben Plesner, MD
Department of Hematology, Vejle Hospital
Vejle, Denmark


ASCO 2014: Dose-dependent efficacy of daratumumab (DARA) as monotherapy in patients with relapsed or refractory multiple myeloma (RR MM)

Henk Lokhorst, MD
University Medical Center Utrecht
Utrecht, the Netherlands


ASCO 2014: A phase I trial of SAR650984, a CD38 monoclonal antibody, in relapsed or refractory multiple myeloma

Thomas G. Martin, MD
University of California SF
San Francisco, California, USA


ASCO 2014: A phase Ib dose escalation trial of SAR650984 (Anti-CD-38 mAb) in combination with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma

Thomas G. Martin, MD
University of California SF
San Francisco, California, USA


Other New Agents And Studies
ASCO 2014: Panorama 1: A randomized, double-blind, phase 3 study of panobinostat or placebo plus bortezomib and dexamethasone in relapsed or relapsed and refractory multiple myeloma

Paul Richardson, MD
Dana-Farber Cancer Institute
Boston, Massachusetts, USA


ASCO 2014: Preliminary safety and efficacy of TH-302, an investigational hypoxia-targeted drug, and dexamethasone (dex) in patients (pts) with relapsed/refractory multiple myeloma (RR MM)

Paul Richardson, MD
Dana-Farber Cancer Institute
Boston, Massachusetts, USA


ASCO 2014: ECOG multiple myeloma (MM) clinical trial (CT) accrual performance evaluation utilizing the NCI–Trial Complexity and Elements Scoring (NCI-TCES) and the NCI Myeloma Steering Committee Accrual Working Group (NCI MYSC AWG) scoring models

Matthias Weiss, MD
Marshfield Clinic
Marshfield, Wisconsin, USA


ASCO 2014: Free light chain assay and cytogenetic abnormalities for identification of high-risk smoldering myeloma

Jeremy Larsen, MD
Mayo Clinic
Rochester, Minnesota, USA


ASCO 2014: Phase 1-2 open-label, multiple-dose, dose-escalation study to evaluate the safety and tolerability of intravenous infusion of SNS01-T, a first-in-class modulator of eukaryotic translation initiation factor 5A (eIF5A) in patients (pts) with relapsed or refractory B-cell malignancies

David Siegel, MD
John Theurer Cancer Center
Hackesack, New Jersey, USA


ASCO 2014: Prevalence of high symptom burden and its impact on functioning and quality of life in patients with multiple myeloma 3-9 months following autologous transplant

Xin Shelley Wang, MD
MD Anderson Cancer Center
Houston, Texas, USA


ASCO 2014: SWOG 1211: A randomized phase I/II study of optimal induction therapy for newly diagnosed high-risk multiple myeloma (HRMM)

Saad Z. Usmani, MD
Levine Cancer Institute - Morehead
Charlotte, North Carolina, USA


ASCO 2014: The Impact of Race and Socio-Economic Status on Survival in Multiple Myeloma

Mark A. Fiala, BS, CCRN
Washington University School of Medicine
Division of Oncology, Department of Medicine
Saint Louis, MO, USA

 


ASCO 2014: A phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone (QUAD) in relapsed and/or refractory multiple myeloma (MM)

David Siegel, MD
John Theurer Cancer Center
Hackensack, New Jersey, USA


Myeloma Minute
March 5, 2015