Selinexor + DRd for Multiple Myeloma

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

73 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single-arm, phase II, open-label trial to investigate the effects of selinexor (S) in combination with daratumumab, lenalidomide, and dexamethasone (DRd) for first-line treatment of multiple myeloma (MM). FDA has approved selinexor plus dexamethasone in multiple myeloma after four prior therapies, and DRd is also already approved by the FDA for multiple myeloma. This study will use all four (S-DRd) together to treat MM as an initial treatment.

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.

What data supports the idea that Selinexor + DRd for Multiple Myeloma is an effective drug?

The available research shows that the combination of Selinexor with Daratumumab and Dexamethasone (SDd) is effective for treating multiple myeloma. In a study with 34 patients, 73% of them responded positively to the treatment, and those who had not previously been treated with Daratumumab had a median time of 12.5 months before the disease worsened. This suggests that the combination is promising, especially for patients who have tried other treatments without success. Compared to another combination involving Selinexor, Bortezomib, and Dexamethasone (SVd), which had a 63% response rate, the SDd combination shows a higher response rate, indicating its potential effectiveness. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination Selinexor, Daratumumab, and Dexamethasone for treating multiple myeloma?

Research shows that the combination of Selinexor, Daratumumab, and Dexamethasone has a promising overall response rate of 73% in patients with relapsed or refractory multiple myeloma who have not previously been treated with Daratumumab. This suggests that the drug combination can be effective in controlling the disease. ^{1 2 3 4 5}

What safety data exists for the treatment of Selinexor + DRd in multiple myeloma?

The combination of Selinexor, Daratumumab, and Dexamethasone (SDd) has been studied for safety in patients with relapsed or refractory multiple myeloma. In a study with 34 patients, common treatment-related adverse events included thrombocytopenia (70.6%), nausea (70.6%), fatigue (61.8%), anemia (61.8%), and neutropenia (50.0%). The maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for Selinexor was determined to be 100 mg once weekly. The treatment was generally well tolerated, with no dose-limiting toxicities reported at this dose. Other studies have shown that Selinexor, when combined with other agents like bortezomib and dexamethasone, has a predictable toxicity profile, with common side effects including thrombocytopenia, anemia, neutropenia, fatigue, nausea, anorexia, and weight loss. These side effects are significant but manageable with aggressive and preemptive care. ^{1 2 3 4 6}

What is the safety profile of Selinexor combined with Daratumumab and Dexamethasone for treating multiple myeloma?

The combination of Selinexor, Daratumumab, and Dexamethasone has been studied for safety in patients with relapsed or refractory multiple myeloma. Common side effects include low platelet counts (thrombocytopenia), nausea, fatigue, low red blood cell counts (anemia), and low white blood cell counts (neutropenia). The treatment was generally well tolerated, with no unexpected side effects reported. ^{1 2 3 4 6}

Is the drug combination of Selinexor, Daratumumab, Dexamethasone, and Lenalidomide promising for treating Multiple Myeloma?

Yes, the combination of Selinexor, Daratumumab, Dexamethasone, and Lenalidomide shows promise for treating Multiple Myeloma. It has a high overall response rate of 73% in patients who haven't been treated with Daratumumab before, and it helps patients live longer without the disease getting worse for about 12.5 months. This suggests it could be a valuable option for patients who have tried other treatments. ^{1 2 3 4 5}

What makes the drug Selinexor + DRd unique for treating multiple myeloma?

The Selinexor + DRd treatment is unique because it combines selinexor, an oral selective inhibitor of nuclear export, with daratumumab and dexamethasone, offering a novel approach for patients with relapsed or refractory multiple myeloma who are resistant to other treatments. This combination is particularly promising for patients whose disease is naïve to daratumumab, showing a high overall response rate and progression-free survival. ^{1 2 3 4 5}

Research Team

Robert M Rifkin, MD, FACP

Principal Investigator

US Oncology Research/McKesson Specialty Health

Eligibility Criteria

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 18 years old or older.

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

You have a detectable disease that meets certain standards.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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, 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]

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 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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Selinexor, daratumumab, and dexamethasone in patients with relapsed or refractory multiple myeloma. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Real World Efficacy and Toxicity of Selinexor: Importance of Patient Characteristics, Dose Intensity and Post Progression Outcomes. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Targeting Nuclear Export Proteins in Multiple Myeloma Therapy. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia. [2021]