A PHASE 1B STUDY USING THE COMBINATION OF SELINEXOR, DARATUMUMAB, AND DEXAMETHASOME IN MULTIPLE MYELOMA PATIENTS PREVIOUSLY EXPOSED TO PROTEASOME INHIBITORS AND IMMUNOMODULATORY DRUGS
Author(s): ,
Cristina Gasparetto
Affiliations:
Duke University Cancer Center,Durham,United States
,
Suzanne Lentzsch
Affiliations:
Columbia University,New York,United States
,
Gary Schiller
Affiliations:
UCLA Ronald Reagan Medical Center,Los Angeles,United States
,
William Bensinger
Affiliations:
Swedish Cancer Center,Seattle,United States
,
Nizar Bahlis
Affiliations:
Southern Alberta Cancer Research Institute,Calgary,Canada
,
Heather Sutherland
Affiliations:
Vancouver General Hospital,Vancouver,Canada
,
Darrell White
Affiliations:
Dalhousie University and QEII Health Sciences Center,Halifax,Canada
,
Michael Sebag
Affiliations:
Royal Victoria Hospital,Montreal,Canada
,
Rami Kotb
Affiliations:
Cancer Care Manitoba,Manitoba,Canada
,
Chris Venner
Affiliations:
Cross Cancer Institute,Edmonton,Canada
,
Richard LeBlanc
Affiliations:
Hôpital Maisonneuve-Rosemont,Montreal,Canada
,
Christine Chen
Affiliations:
Princess Margaret Cancer Center,Toronto,Canada
,
Aldo Del Col
Affiliations:
Myeloma Canada,Laval,Canada
,
Michael Kauffman
Affiliations:
Karyopharm Therapeutics,Newton,United States
,
Sharon Shacham
Affiliations:
Karyopharm Therapeutics,Newton,United States
,
Jacqueline Jeha
Affiliations:
Karyopharm Therapeutics,Newton,United States
,
Jean-Richard Saint-Martin
Affiliations:
Karyopharm Therapeutics,Newton,United States
,
Jatin Shah
Affiliations:
Karyopharm Therapeutics,Newton,United States
,
Joel Turner
Affiliations:
Moffitt Cancer Center,Tampa,United States
,
Dan Sullivan
Affiliations:
Moffitt Cancer Center,Tampa,United States
Brea Lipe
Affiliations:
University of Rochester Medical College,New York,United States
EHA Library. Gasparetto C. 06/16/18; 215629; PS1329
Cristina Gasparetto
Cristina Gasparetto
Contributions
Abstract

Abstract: PS1329

Type: Poster Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 17:30 - 19:00

Location: Poster area

Background
Selinexor is a first-in-class Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates Exportin 1 (XPO1). Selinexor, as a single agent, or in combination with PIs or IMiDs, has shown anti-MM activity in patients (pts) with relapsed or refractory multiple myeloma (RRMM). Daratumumab, an anti-CD38 monoclonal antibody, is approved for the treatment of RRMM. In CD138(+) myeloma cells, from newly diagnosed MM patients, were sensitized to the combination of selinexor and daratumumab as compared to single agent selinexor (p=0.005) or Dara (p=0.004).

Aims
This Ph 1b (NCT02343042), dose escalation study was designed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the safety, tolerability and efficacy of the combination of selinexor, daratumumab, and low dose dex (SDd) in pts with RRMM.

Methods
Pts were eligible if they had RRMM and had received ≥ 3 prior therapies, including a PI and IMiD. Selinexor was independently dosed escalated in 2 concurrent cohorts: once-weekly (QW, at 100 mg) or twice-weekly (BIW, at 60 mg) regimens. Daratumumab (16 mg/kg IV) was administered QW and dexamethasone (dex) was given orally 40 mg QW or 20 mg BIW.

Results
As of Feb 27th 2018, 13 pts (7 males / 6 females) have been enrolled. Three pts have been enrolled into the 60 mg BIW and 10 pts in the 100 mg QW cohorts. Pts have a median age of 67 years and a median of 4 (range, 2 – 10) prior treatment regimens. Adverse events include: fatigue (9 pts), thrombocytopenia (8 pts), neutropenia (7 pts), and nausea (5 pts). Two DLT’s were reported in the 60 mg BIW cohort: G3 thrombocytopenia and G2 fatigue requiring dose reduction in selinexor to 100 mg QW. In the 100 mg QW cohort, 6 pts enrolled, 5 evaluable, with no DLTs; enrollment in this cohort is ongoing. A total of 10 pts were evaluable for response. In 8 dara-naïve pts, the ORR was 88% (4 VGPR, 3 PR, 1 PD), two PRs unconfirmed, and responses usually occurred within 1 cycle of treament. In the 2 pts with daratumumab refractory MM, there was one PD and one SD. Based on tolerability and efficacy, the RP2D of SDd is selinexor 100 mg, daratumumab 16 mg/kg and dex 40 mg, administered QW.

Conclusion
Selinexor 100 mg QW, can be combined safely with standard dose/schedule daratumumab and dex.  The preliminary activiy with an ORR of 88% in RRMM patients who are dara naïve is promising. Enrollment is ongoing and updated data from the full phase 1 will be presented. 

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Dexamethasone, Multiple Myeloma

Abstract: PS1329

Type: Poster Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 17:30 - 19:00

Location: Poster area

Background
Selinexor is a first-in-class Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates Exportin 1 (XPO1). Selinexor, as a single agent, or in combination with PIs or IMiDs, has shown anti-MM activity in patients (pts) with relapsed or refractory multiple myeloma (RRMM). Daratumumab, an anti-CD38 monoclonal antibody, is approved for the treatment of RRMM. In CD138(+) myeloma cells, from newly diagnosed MM patients, were sensitized to the combination of selinexor and daratumumab as compared to single agent selinexor (p=0.005) or Dara (p=0.004).

Aims
This Ph 1b (NCT02343042), dose escalation study was designed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the safety, tolerability and efficacy of the combination of selinexor, daratumumab, and low dose dex (SDd) in pts with RRMM.

Methods
Pts were eligible if they had RRMM and had received ≥ 3 prior therapies, including a PI and IMiD. Selinexor was independently dosed escalated in 2 concurrent cohorts: once-weekly (QW, at 100 mg) or twice-weekly (BIW, at 60 mg) regimens. Daratumumab (16 mg/kg IV) was administered QW and dexamethasone (dex) was given orally 40 mg QW or 20 mg BIW.

Results
As of Feb 27th 2018, 13 pts (7 males / 6 females) have been enrolled. Three pts have been enrolled into the 60 mg BIW and 10 pts in the 100 mg QW cohorts. Pts have a median age of 67 years and a median of 4 (range, 2 – 10) prior treatment regimens. Adverse events include: fatigue (9 pts), thrombocytopenia (8 pts), neutropenia (7 pts), and nausea (5 pts). Two DLT’s were reported in the 60 mg BIW cohort: G3 thrombocytopenia and G2 fatigue requiring dose reduction in selinexor to 100 mg QW. In the 100 mg QW cohort, 6 pts enrolled, 5 evaluable, with no DLTs; enrollment in this cohort is ongoing. A total of 10 pts were evaluable for response. In 8 dara-naïve pts, the ORR was 88% (4 VGPR, 3 PR, 1 PD), two PRs unconfirmed, and responses usually occurred within 1 cycle of treament. In the 2 pts with daratumumab refractory MM, there was one PD and one SD. Based on tolerability and efficacy, the RP2D of SDd is selinexor 100 mg, daratumumab 16 mg/kg and dex 40 mg, administered QW.

Conclusion
Selinexor 100 mg QW, can be combined safely with standard dose/schedule daratumumab and dex.  The preliminary activiy with an ORR of 88% in RRMM patients who are dara naïve is promising. Enrollment is ongoing and updated data from the full phase 1 will be presented. 

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Dexamethasone, Multiple Myeloma

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