Selinexor + DRd for Multiple Myeloma

Not currently recruiting at 10 trial locations

Overseen By Sharan Aranha, BDS, MHA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: US Oncology Research

Disqualifiers: HIV, Hepatitis B, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of four drugs—selinexor (a new potential drug), daratumumab, lenalidomide, and dexamethasone—for the initial treatment of multiple myeloma, a type of blood cancer. The goal is to determine the effectiveness of this combination for individuals who have not yet received other treatments for their condition. The trial seeks participants with diagnosed multiple myeloma who have measurable disease and have not yet started treatment.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, since this is a first-line treatment for multiple myeloma, it's likely that you may need to adjust your current medications. Please consult with the trial investigators for specific guidance.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that selinexor, when combined with other treatments, can be safe for people with multiple myeloma. Patients who previously took selinexor with other medications generally found it safe, though some side effects were reported. The FDA has approved selinexor for multiple myeloma after other treatments, indicating a level of safety in humans.

Adding daratumumab, lenalidomide, and dexamethasone to selinexor is not entirely new. The combination of daratumumab with lenalidomide and dexamethasone (DRd) is already approved for treating multiple myeloma, providing existing safety information for these medications used together.

While using all four medications (selinexor, daratumumab, lenalidomide, and dexamethasone) as a first treatment is new, the individual components have been studied and approved. This suggests the combination may be well-tolerated, but monitoring for side effects is important. The trial will carefully monitor participants for any unwanted effects to ensure safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Unlike the standard treatments for multiple myeloma, which often include drugs like bortezomib, thalidomide, or pomalidomide, the combination treatment of Selinexor plus DRd (daratumumab, lenalidomide, and dexamethasone) offers a new approach. Selinexor works by selectively inhibiting nuclear export, which disrupts cancer cell growth and survival, providing a unique mechanism of action compared to traditional therapies. Researchers are excited about this combination because Selinexor may enhance the effectiveness of the other drugs, potentially leading to better outcomes for patients. Additionally, the dosing strategy for Selinexor is designed to optimize its efficacy while managing side effects, which is a promising approach for improving patient quality of life.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

In this trial, participants will receive a combination of selinexor with the drugs daratumumab, lenalidomide, and dexamethasone (DRd) to treat multiple myeloma, a type of blood cancer. Studies have shown that selinexor with DRd can effectively help patients whose cancer returned after treatment. Clinical data shows that 74% of patients responded well to similar drug combinations. Selinexor also slows the disease when used with other treatments. This trial aims to combine these proven therapies for better results in newly diagnosed patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Robert M Rifkin, MD, FACP

Principal Investigator

US Oncology Research/McKesson Specialty Health

Are You a Good Fit for This Trial?

Adults with untreated multiple myeloma can join this trial. They must be able to follow the study plan and use effective birth control if they can have children. People who've had major surgery recently, have brain involvement by myeloma, HIV, hepatitis B or C, serious heart issues, or certain blood conditions cannot participate.

Inclusion Criteria

I am able to care for myself and perform daily activities.

You have a detectable disease that meets certain standards.

My myeloma has not been treated before.

Exclusion Criteria

I do not have any health conditions that could affect the study.

You are thinking about getting pregnant.

My multiple myeloma has affected my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Selinexor in combination with daratumumab, lenalidomide, and dexamethasone for first-line treatment of multiple myeloma

6 months

Weekly visits for the first 2 cycles, bi-weekly visits for cycles 3-6, and monthly visits thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab
• Dexamethasone Oral
• Lenalidomide
• Selinexor

Trial Overview The trial is testing a combination of four drugs: Selinexor plus Daratumumab, Lenalidomide, and Dexamethasone (S-DRd) as a first-line treatment for multiple myeloma. It's an open-label phase II study where everyone gets the same treatment.

How Is the Trial Designed?

Group I: Selinexor plus DRd Experimental Treatment 4 Interventions

1. Lenalidomide 15 mg orally on Days 1-21 of each 28-day cycle 2. Dexamethasone 40 mg on Days 1, 8, 15, 22 of each cycle. However, those \>75 years old may be administered a weekly dose of 20 mg dexamethasone. 3. Daratumumab 1800 mg subcutaneous injection once weekly in Cycles 1 and 2, every 2 weeks in cycles 3 to 6, and every 4 weeks thereafter. 4. Selinexor 60 mg on Days 1, 8, 15, of cycles 1-3, with a planned dose-reduction to 40 mg on Days 1, 8, 15 for cycles beyond 3. If patient was previously dose reduced prior to cycle 4, then at cycle 4 planned dose reduction, you will again decrease dose by 1 level.

Daratumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

Who Is Running the Clinical Trial?

US Oncology Research

Lead Sponsor

Trials

38

Recruited

17,400+

Karyopharm Therapeutics Inc

Industry Sponsor

Trials

89

Recruited

7,200+

Richard Paulson

Karyopharm Therapeutics Inc

Chief Executive Officer since 2021

MBA from the University of Toronto's Rotman School of Management

Reshma Rangwala

Karyopharm Therapeutics Inc

Chief Medical Officer since 2023

MD, PhD

Published Research Related to This Trial

Selinexor, when combined with low-dose bortezomib and dexamethasone, showed a 63% overall response rate in treating relapsed or refractory multiple myeloma, with particularly high efficacy in patients not previously resistant to proteasome inhibitors (84% response rate).

The treatment was generally well-tolerated, with the most common severe side effects being thrombocytopenia (45%) and neutropenia (24%), while the recommended phase 2 dose was established as selinexor 100 mg once weekly, bortezomib 1.3 mg/m2 once weekly, and dexamethasone 40 mg once weekly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma. Bahlis, NJ., Sutherland, H., White, D., et al.[2021]

Selinexor, a first-in-class selective inhibitor of nuclear export (XPO1), has shown significant efficacy in treating relapsed refractory multiple myeloma (RRMM), leading to its FDA approval in combination with dexamethasone based on results from the pivotal phase II STORM trial.

The phase III BOSTON trial demonstrated that selinexor combined with bortezomib and dexamethasone is superior to the standard treatment of bortezomib and dexamethasone alone, although it is associated with a predictable toxicity profile that requires careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Nuclear Export Proteins in Multiple Myeloma Therapy. Richard, S., Jagannath, S.[2022]

In a phase 1 study involving 84 patients with relapsed or refractory multiple myeloma, the combination of oral selinexor and dexamethasone showed a significant increase in efficacy, achieving a 50% objective response rate compared to a modest 4% with selinexor alone.

The most common side effects were manageable and primarily grade 1 or 2, with thrombocytopenia being the most notable severe adverse event at 45%, indicating that while selinexor is effective, monitoring for blood-related side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia. Chen, C., Siegel, D., Gutierrez, M., et al.[2021]

Selinexor, when used in combination with dexamethasone or bortezomib and dexamethasone, showed an overall response rate of 29.5% in 44 patients with relapsed or refractory myeloma, indicating its efficacy as a treatment option.

The most common side effects included fatigue and thrombocytopenia, with 56% of patients requiring dose reductions; however, these adjustments did not negatively impact progression-free survival, suggesting that selinexor can be managed safely in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real World Efficacy and Toxicity of Selinexor: Importance of Patient Characteristics, Dose Intensity and Post Progression Outcomes. Kastritis, E., Gavriatopoulou, M., Solia, E., et al.[2023]

In a phase I trial involving 21 patients with relapsed/refractory multiple myeloma, the combination of selinexor, carfilzomib, and dexamethasone was found to be tolerable, with a recommended phase II dose established at selinexor 60 mg, carfilzomib 20/27 mg/m2, and dexamethasone 20 mg.

The treatment resulted in significant response rates, with 71% of patients achieving at least a minimal response and a median overall survival of 22.4 months, demonstrating its efficacy even in patients who were refractory to carfilzomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma. Jakubowiak, AJ., Jasielec, JK., Rosenbaum, CA., et al.[2023]

In a study of 34 patients with relapsed refractory multiple myeloma, the combination of selinexor, daratumumab, and dexamethasone showed a promising overall response rate of 73% and a median progression-free survival of 12.5 months in patients who had not previously received daratumumab.

The maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for selinexor was determined to be 100 mg once weekly, with common side effects including thrombocytopenia and nausea, indicating that the treatment regimen is generally well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor, daratumumab, and dexamethasone in patients with relapsed or refractory multiple myeloma. Gasparetto, C., Lentzsch, S., Schiller, G., et al.[2022]

Citations

1. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/6739/501309/Selinexor-Daratumumab-and-Dexamethasone-for

Selinexor, Daratumumab and Dexamethasone for Patients ... This real-world study demonstrates that SDd combination therapy led to early, deep responses in lenalidomide-refractory multiple myeloma patients at their ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9176052/

Selinexor, daratumumab, and dexamethasone in patients ... Survival of patients with multiple myeloma (MM) has improved significantly with the introduction of new agents over the past 20 years.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04782687

Study of Selinexor Plus DRd for Newly Diagnosed Multiple ... Clinical data demonstrate an ORR of 74% in patients with relapsed myeloma treated with Selinexor, daratumumab, and dexamethasone. The rationale for the ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124098768

Selinexor Combined with Daratumumab, Thalidomide, and ... This study aims to evaluate the efficacy and safety of a regimen combining selinexor with daratumumab (Dara), thalidomide, and dexamethasone for patients with ...

5. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK603404/

Selinexor (Xpovio) - NCBI Bookshelf Evidence from a clinical trial demonstrated that Xpovio delayed progression of multiple myeloma when added to bortezomib and dexamethasone. Xpovio meets ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06169215

NCT06169215 | Comparing the Combination of Selinexor- ... This phase II trial compares the combination of selinexor, daratumumab and hyaluronidase-fihj (daratumumab), velcade (bortezomib), and dexamethasone ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12497632/

Lower dose and weekly schedules of selinexor in multiple ... Selinexor, a first-in-class, oral exportin-1 inhibitor, showed activity in penta-refractory multiple myeloma (MM) in early trial exploration; ...

8. clinicaltrial.be clinicaltrial.be/en/details/46811?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Study of Selinexor Plus DRd for Newly Diagnosed Multiple... Preclinical data demonstrated that patient-derived MM cells were sensitized to the combination of Selinexor and daratumumab compared to the single agents.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02343042

Study Details | NCT02343042 | Selinexor and Backbone ... Efficacy and safety of once weekly selinexor 40 mg versus 60 mg with pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Front ...

10. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(23)00184-2/fulltext

Selinexor-Based Triplet Regimens in Patients With Multiple ... Preclinical and ex vivo data have suggested that selinexor may synergize with other anti-MM therapies, resensitize cells to anti-myeloma ...