Selinexor, Dexamethasone and Bortezomib in Patients with Multiple Myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karyopharm Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

25 Jun 2020 → ongoing

Decision date (initial)

2024-09-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Karyopharm Therapeutics Inc.

External identifiers

EU CT number

2024-511608-18-00

EudraCT number

2020-000821-22

ClinicalTrials.gov

NCT04414475

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Pharmacokinetic, Pharmacogenetic, Safety, Therapy

To evaluate the efficacy of treatment in the 4 arms:
- Selinexor 40 mg plus dexamethasone 20 mg in patients with pentarefractory multiple myeloma twice/week,
- Selinexor 80 mg plus dexamethasone 20 mg in patients with pentarefractory multiple myeloma twice/week,
- Selinexor 100 mg plus dexamethasone 40mg in patients with pentarefractory multiple myeloma once/week,
- Selinexor 100 mg in combination with dexamethasone 40 mg and bortezomib 1.3 mg/m2 in patients with triple-class refractory multiple myeloma, once/week (without week 5 dosing).

Secondary objectives 2

1. To assess the antitumor activity of treatment in the 4 arms;
2. To assess the safety and tolerability of treatment in the 4 arms.

Conditions and MedDRA coding

Penta-refractory multiple myeloma and triple-class refractory multiple myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥18 years at the time of signing informed consent.
2. Written informed consent signed in accordance with federal, local, and institutional guidelines.
3. Measurable multiple myeloma (MM) based on International Myeloma Working Group (IMWG) guidelines as defined by at least one of the following: a. Serum M-protein ≥0.5 g/dL by serum protein electrophoresis (SPEP) or, for Immunoglobulin (Ig) A myeloma, by quantitative IgA. b. Urinary M-protein excretion ≥200 mg/24 hours. c. Free light chain (FLC) ≥100 mg/L, provided that the FLC ratio is abnormal.
4. Only for Arms Sd-40 BIW, Sd-100 QW and Sd-80 BIW prior to PV 5.0: Patients must have RRMM and have previously received at least 4 anti-MM prior therapies and have MM that is refractory to previous treatment with at least 2 PIs, at least 2 IMiDs, and 1 anti-CD38 monoclonal antibody. Refractory is defined as ≤25% response to therapy, or progression during therapy or progression within 60 days after completion of therapy. Only for Arms Sd-40 BIW and Sd-100 QW as of PV 5.0: Patients must have RR MM and have been previously treated with ≥3 anti-MM therapies (with exposure to at least 2 PI drugs, at least 2 IMiDs, and 1 anti-CD38 monoclonal antibody), and be refractory to at least 1 drug of each class (PI/IMiD/anti-CD38). Refractory is defined as ≤25% response to therapy or progression during therapy or progression within 60 days after completion of therapy.
5. Only for arm SVd: Patients must have previously received 1 to 5 anti- MM prior therapies and have MM that is refractory to previous treatment with at least 1 PI, at least 1 IMiD, and 1 anti-CD38 monoclonal antibody.
6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
7. Female patients of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for 7 months for female and 4 months for male following the discontinuation of study treatment.

Exclusion criteria 21

1. Active plasma cell leukemia.
2. Documented systemic amyloid light chain amyloidosis.
3. Active central nervous system MM.
4. Only for Arm SVd: Greater than Grade 2 peripheral neuropathy or Grade ≥2 peripheral neuropathy with pain at baseline, regardless of whether or not the patient is currently receiving medication.
5. Radiation, chemotherapy, immunotherapy, or any other anticancer therapy (including investigational therapies) ≤2 weeks prior to Cycle 1 Day 1 (C1D1). (Steroids are permitted up to 1 pulse of 40 mg per day for 4 days in the 2 weeks prior to C1D1.)
6. Active graft vs. host disease (after allogeneic stem cell transplantation) at C1D1.
7. Ongoing clinically significant non-hematological toxicities from prior treatments that are Grade >2 at C1D1.
8. Inadequate hepatic function defined as total bilirubin ≥2x upper limit of normal (ULN) (≥3x ULN for patients with Gilbert’s syndrome), aspartate transaminase (AST) ≥2.5x ULN, and alanine transaminase (ALT) ≥2.5x ULN.
9. Inadequate renal function defined as estimated creatinine clearance of <20 mL/min, calculated using the formula of Cockroft and Gault (Section 9.5.4).
10. Inadequate hematopoietic function defined as the following: a. Absolute neutrophil count (ANC) <1,000/mm3 b. Platelet count <75,000/mm3 c. Hemoglobin (Hb) level <8.0 g/dL
11. Life expectancy of <4 months, based on the opinion of the Investigator.
12. Major surgery within 4 weeks prior to C1D1.
13. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to first dose.
14. Active gastrointestinal dysfunction interfering with the ability to swallow tablets, or any gastrointestinal dysfunction that could interfere with absorption of the study treatment.
15. Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus RNA or hepatitis B virus surface antigen.
16. Female patients who are pregnant or lactating.
17. Known intolerance, hypersensitivity, or contraindication to glucocorticoid therapy at C1D1.
18. Concurrent therapy with approved or investigational anticancer therapeutic including topical therapies.
19. Prior exposure to a SINE compound, including selinexor.
20. Serious, active psychiatric or active medical conditions which, in the opinion of the Investigator or the Sponsor, could interfere with participation in the study.
21. Contraindication to any of the required concomitant drugs or supportive treatments.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR defined as the proportion of patients who achieve stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) as assessed by the Investigator based on International Myeloma Working Group (IMWG) response criteria will be analyzed separately for each arm

Secondary endpoints 2

1. The following endpoints will be analyzed separately for each arm: • Duration of response (DOR) • Clinical benefit rate (CBR) • Disease control rate (DCR) • Progression-free survival (PFS) • Overall survival (OS) • Time to next treatment (TTNT)
2. The safety and tolerability of study drug will be evaluated based on AE reports, vital signs, and clinical laboratory results by means of the occurrence, nature, and severity of AEs as categorized by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karyopharm Therapeutics Inc.

Sponsor organisation

Karyopharm Therapeutics Inc.

Address

85 Wells Avenue

City

Newton

Postcode

02459-3298

Country

United States

Scientific contact point

Organisation

Karyopharm Therapeutics Inc.

Contact name

Clinical Trials Information Desk

Public contact point

Organisation

Karyopharm Therapeutics Inc.

Contact name

Clinical Trials Information Desk

Third parties 9

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications