NCT02336815: STORM

Selinexor Treatment of Refractory Myeloma

Completed Phase 2 Results posted Last updated 26 January 2023

What this trial tests

Phase 2 trial testing Selinexor in Multiple Myeloma in 202 participants. Completed in 26 July 2019.

Timeline

26 May 2015

Primary endpoint
26 July 2019

26 July 2019

Quick facts

Lead sponsor	Karyopharm Therapeutics Inc
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	202
Start date	26 May 2015
Primary completion	26 July 2019
Estimated completion	26 July 2019
Sites	61 locations across France, Greece, Belgium, Austria, Germany, United States

Drugs / interventions tested

• Selinexor — full drug profile →
• Dexamethasone (dexamethasone) — full drug profile →

Conditions studied

• Multiple Myeloma — all drugs for Multiple Myeloma →

Sponsor

Karyopharm Therapeutics Inc — full company profile →

Who can join

18 and older, any sex, with Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Part 2: Percentage of Participants With Overall Response Rate (ORR) Per International MyelomaWorking Group (IMWG) as Assessed by an Independent Review Committee (IRC) Primary · Baseline until disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months)

IRC assessed ORR per 2016 IMWG criteria: Percentage of participants who experienced Partial response (PR): greater than or equal to (\>=) 50 percent (%) reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to lesser than (\<) 200 mg per 24 hours; Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tiss

Group	Value	95% CI
Part 2	26.2	18.7 – 35.0

Part 1: Duration of Response (DoR) Per IMWG as Assessed by IRC Secondary · First response subsequently confirmed to disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 13 months)

IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; Progressive disease (PD): Increase of 25% from lowest confirmed response v

Group	Value	95% CI
Part 1	6.2	3.6 – 9.8

Part 2: Duration of Response (DoR) Per IMWG as Assessed by an IRC Secondary · First response subsequently confirmed to disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months)

IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; Progressive disease (PD): Increase of 25% from lowest confirmed response v

Group	Value	95% CI
Part 2	4.4	3.7 – 10.8

Part 1: Percentage of Participants With Clinical Benefit Rate (CBR) ) Per IMWG as Assessed by IRC Secondary · Baseline up to a maximum of 13 months

IRC assessed CBR per 2016 IMWG criteria: Percentage of participants with a confirmed minimal response (MR) or better (PR, VGPR, CR or sCR) before confirmed disease progression or initiating new MM treatment. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90%

Group	Value	95% CI
Part 1	31.6	21.6 – 43.1

Part 2: Percentage of Participants With Clinical Benefit Rate (CBR) Per IMWG as Assessed by IRC Secondary · Baseline up to a maximum of 17 months

IRC assessed CBR per 2016 IMWG criteria: Percentage of participants with a confirmed minimal response (MR) or better (PR, VGPR, CR or sCR) before confirmed disease progression or initiating new MM treatment. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90%

Group	Value	95% CI
Part 2	39.3	30.6 – 48.6

Part 1: Duration of Clinical Benefit Per IMWG as Assessed by IRC Secondary · First response subsequently confirmed to disease progression, or death, whichever occurred first (maximum duration of 13 months)

IRC assessed duration of clinical benefit per 2016 IMWG criteria: Duration from first response (at least MR) to time of IRC-determined PD or death due to disease progression, whichever occurs first. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absol

Group	Value	95% CI
Part 1	5.6	4.4 – 10.3

Part 2: Duration of Clinical Benefit Per IMWG as Assessed by IRC Secondary · First response subsequently confirmed to disease progression, or death, whichever occurred first (maximum duration of 17 months)

IRC assessed duration of clinical benefit per 2016 IMWG criteria: Duration from first response (at least MR) to time of IRC-determined PD or death due to disease progression, whichever occurs first. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absol

Group	Value	95% CI
Part 2	3.8	3.2 – 10.9

Part 2: Disease Control Rate (DCR) Secondary · Every 12 weeks until progressive disease or death due to any cause, up to 17 months

DCR was defined as the percentage of participants who achieved stable disease (SD) or better (MR, PR, VGPR, CR, sCR) for a minimum of 12 weeks. Stable disease (SD): Not recommended for use as an indicator of response; stability of disease was best described by providing the time to progression (TTP) estimates. MR: \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. PR: \>=50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixati

Group	Value	95% CI
Part 2	44.3	35.3 – 53.5

Part 1: Progression Free Survival (PFS) Per IMWG as Assessed by IRC Secondary · From start of study treatment to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 13 months)

IRC assessed PFS per 2016 IMWG criteria: Duration from start of study treatment until IRC-determined progressive disease (PD) or death from any cause, whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.

Group	Value	95% CI
Part 1	4.7	3.3 – 7.6

Part 2: Progression Free Survival (PFS) Per IMWG as Assessed by IRC Secondary · From start of study treatment to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 17 months)

IRC assessed PFS per 2016 IMWG criteria: Duration from start of study treatment until IRC-determined progressive disease (PD) or death from any cause, whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.

Group	Value	95% CI
Part 2	3.7	2.8 – 4.7

Part 1: Time to Progression (TTP) Per IMWG as Assessed by IRC Secondary · From start of study treatment to progression of disease or death, whichever occurred first (maximum duration of 13 months)

IRC assessed TTP per 2016 IMWG criteria: Duration from start of study treatment until PD or death due to PD (per IRC), whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.

Group	Value	95% CI
Part 1	5.5	3.3 – 10.7

Part 2: Time to Progression (TTP) Per IMWG as Assessed by IRC Secondary · From start of study treatment to progression of disease or death, whichever occurred first (maximum duration of 17 months)

IRC assessed TTP per 2016 IMWG criteria: Duration from start of study treatment until PD or death due to PD (per IRC), whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.

Group	Value	95% CI
Part 2	4.1	3.0 – 6.2

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline to 30 days after last dose of study treatment (maximum duration of 18 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1

Serious: 45/79 (57%)

Deaths: 20/79

Part 2

Serious: 78/123 (63%)

Deaths: 28/123

Serious adverse events (126 terms)

Reaction	System	Part 1	Part 2
Pneumonia	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Fatigue	General disorders	—	—
General physical health deterioration	General disorders	—	—
Influenza	Infections and infestations	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—
Hypercalcaemia	Metabolism and nutrition disorders	—	—
Confusional state	Psychiatric disorders	—	—
Mental status changes	Psychiatric disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Asthenia	General disorders	—	—
Bacteraemia	Infections and infestations	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Cardio-respiratory arrest	Cardiac disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Parainfluenzae virus infection	Infections and infestations	—	—
Clostridium difficile infection	Infections and infestations	—	—
Escherichia bacteraemia	Infections and infestations	—	—

Other adverse events (56 terms — click to expand)

Reaction	System	Part 1	Part 2
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Fatigue	General disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Weight decreased	Investigations	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Neutropenia	Blood and lymphatic system disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—
Leukopenia	Blood and lymphatic system disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Insomnia	Psychiatric disorders	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—
Asthenia	General disorders	—	—
Dizziness	Nervous system disorders	—	—
Pyrexia	General disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Oedema peripheral	General disorders	—	—
Vision blurred	Eye disorders	—	—
Fall	Injury, poisoning and procedural complications	—	—
Alanine aminotransferase increased	Investigations	—	—
Hypocalcaemia	Metabolism and nutrition disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Aspartate aminotransferase increased	Investigations	—	—
Bone pain	Musculoskeletal and connective tissue disorders	—	—
Headache	Nervous system disorders	—	—
Confusional state	Psychiatric disorders	—	—
Pneumonia	Infections and infestations	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Tachycardia	Cardiac disorders	—	—

Most-reported serious reactions: Pneumonia, Sepsis, Thrombocytopenia, Anaemia, Fatigue, General physical health deterioration, Influenza, Hyponatraemia.

Data from ClinicalTrials.gov NCT02336815 adverse events section.

Sponsor's own description

This is a Phase 2b, single-arm, open-label, multicenter study of selinexor 80 mg plus dexamethasone 20 mg (Sd) dosed twice weekly in four-week cycles, in patients with penta-refractory MM (Parts 1 and 2) or quad refractory MM (Part 1 only).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma.
   Chari A, Vogl DT, Gavriatopoulou M, Nooka AK, et al · · 2019 · cited 501× · PMID 31433920 · DOI 10.1056/nejmoa1903455
2. XPO1-dependent nuclear export as a target for cancer therapy.
   Azizian NG, Li Y. · · 2020 · cited 183× · PMID 32487143 · DOI 10.1186/s13045-020-00903-4
3. Understanding and targeting resistance mechanisms in cancer.
   Lei ZN, Tian Q, Teng QX, Wurpel JND, et al · · 2023 · cited 174× · PMID 37229486 · DOI 10.1002/mco2.265
4. Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma.
   Vogl DT, Dingli D, Cornell RF, Huff CA, et al · · 2018 · cited 125× · PMID 29381435 · DOI 10.1200/jco.2017.75.5207
5. The past, present, and future of CRM1/XPO1 inhibitors.
   Wang AY, Liu H. · · 2019 · cited 85× · PMID 30976603 · DOI 10.21037/sci.2019.02.03
6. Promising therapies in multiple myeloma.
   Bianchi G, Richardson PG, Anderson KC. · · 2015 · cited 69× · PMID 26031917 · DOI 10.1182/blood-2015-03-575365
7. XPO1 in B cell hematological malignancies: from recurrent somatic mutations to targeted therapy.
   Camus V, Miloudi H, Taly A, Sola B, et al · · 2017 · cited 67× · PMID 28196522 · DOI 10.1186/s13045-017-0412-4
8. Role of Small Molecule Targeted Compounds in Cancer: Progress, Opportunities, and Challenges.
   Sun G, Rong D, Li Z, Sun G, et al · · 2021 · cited 59× · PMID 34568317 · DOI 10.3389/fcell.2021.694363