KPT-8602 for Multiple Myeloma

No longer recruiting at 46 trial locations

Overseen By Karyopharm Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Karyopharm Therapeutics Inc

Must be taking: Corticosteroids

Disqualifiers: Pregnancy, Cardiac diseases, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, KPT-8602 (also known as Eltanexor), for several cancers, including multiple myeloma, colorectal cancer, prostate cancer, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). The goal is to determine the safety and effectiveness of KPT-8602 at various doses. The trial includes different arms; some participants may receive KPT-8602 alone, while others may receive it with another treatment. This study suits individuals whose cancer has returned or not responded to other treatments, such as those with multiple myeloma who have undergone at least three different treatments. Participants should have specific cancer types and have experienced disease progression after previous treatments. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, participants in some parts of the study must have recovered from previous treatments and may need to stop certain therapies before starting the trial. It's best to discuss your specific medications with the study team.

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

Research has shown that KPT-8602, a new type of medication, has been generally well-tolerated in past studies for various conditions. In patients with relapsed or refractory multiple myeloma (RRMM), KPT-8602 was safe, with manageable side effects. The most common side effects were tiredness and nausea, often expected with cancer treatments.

For acute myeloid leukemia (AML), the drug was well-tolerated and showed promise in fighting cancer cells. Patients did not experience severe or unexpected side effects, suggesting it is safe.

In studies on myelodysplastic syndrome (MDS), KPT-8602 was also safe and well-tolerated. As in RRMM, the most common side effects were mild, such as tiredness and nausea.

While these findings suggest KPT-8602 is generally safe, safety can vary based on individual health conditions and treatments. Participants should consult their healthcare providers to understand how KPT-8602 might affect them personally. ^{1 2 3 4 5}

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

Most treatments for multiple myeloma, like chemotherapy and targeted therapies, work by killing rapidly dividing cells or targeting specific proteins on cancer cells. But KPT-8602 works differently, targeting the nuclear export protein XPO1. This unique mechanism can disrupt the cancer cell's survival process, potentially making it effective even in cases where other treatments have failed. Researchers are excited about KPT-8602 because it offers a novel approach that might work against resistant forms of multiple myeloma, with potentially fewer side effects due to its targeted nature.

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

Research has shown that KPT-8602, also known as eltanexor, holds promise for treating multiple myeloma (MM) and other cancers. In this trial, participants with relapsed or hard-to-treat multiple myeloma (RRMM) will receive KPT-8602 in different treatment arms. The drug blocks a protein called XPO1, which moves cancer-related substances out of the cell's control center, the nucleus. By blocking this protein, KPT-8602 can help stop cancer cells from growing. Early studies found that KPT-8602 was well tolerated and effective against cancer cells, making it a hopeful option for those with difficult-to-treat cancers. ^{2 4 6 7 8}

Who Is on the Research Team?

Jatin Shah, MD

Principal Investigator

Karyopharm Therapeutics Inc

Eric Sbar VP of Clinical Development, DO

Principal Investigator

Karyopharm Therapeutics Inc

Reshma Rangwala, MD, PhD

Principal Investigator

Karyopharm Therapeutics Inc

Are You a Good Fit for This Trial?

Adults over 18 with certain relapsed/refractory cancers (like multiple myeloma, colorectal cancer) can join. They need good kidney and liver function, must follow contraception rules based on their condition, and agree to protocol requirements like biopsies. Those with brain metastasis, recent major surgery, severe infections or heart issues cannot participate.

Inclusion Criteria

My liver is functioning within the required limits for the trial.

Written informed consent signed prior to any screening procedures and in accordance with federal, local, and institutional guidelines

Contraception requirements based on specific indication

Exclusion Criteria

I haven't needed strong IV drugs for a severe infection in the last week.

You have a history of HIV or active hepatitis A, B, or C infection.

I have not had major surgery in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Phase 1)

Participants receive escalating doses of KPT-8602 to assess safety and tolerability

Varies by participant

Dose Expansion (Phase 2)

Participants receive KPT-8602 at recommended Phase 2 doses to assess efficacy

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KPT-8602

Trial Overview The trial is testing KPT-8602's safety and effectiveness in patients with specific advanced cancers. It includes a dose escalation phase to find the right amount of drug that's safe and a dose expansion phase to see how well it works at that dose.

How Is the Trial Designed?

Group I: Part H: AML Maintenance Therapy- KPT-8602 single agent Experimental Treatment 1 Intervention

Participants with high-risk acute myeloid leukemia (AML) prior to transplant will be enrolled to receive maintenance therapy with KPT-8602 post-allogeneic stem cell transplantation. The dose for KPT-8602 will be 10 mg (RP2D from Part F) oral, to be administered once daily from Day 1 to Day 21 (Weeks 1 to 3) on a 28-day cycle.

Group II: Part G: Newly Diagnosed Intermediate/High-Risk MDS -KPT-8602 with ASTX727 Experimental Treatment 2 Interventions

Participants will receive KPT-8602 once daily at escalated doses. The starting dose for KPT-8602 is 5 mg orally once daily from Day 8 to Day 28 (Weeks 2 to 4) on a 28-day cycle in combination with ASTX727.

Group III: Part F: High-risk Myelodysplastic Syndrome (MDS)- KPT-8602 single agent Experimental Treatment 1 Intervention

Participants were treated with KPT-8602 at a dose and schedule that had been cleared in Part A. In select cases (for example, participants achieving stable disease \[SD\], hematological improvement \[HI\], partial response \[PR\] and tolerating treatment, etc.), the dose may be escalated 1 level based on safety and efficacy considerations (completed).

Group IV: Part F Phase 2: RR High-risk MDS- KPT-8602 single agent Experimental Treatment 1 Intervention

Participants will be enrolled at recommended Phase 2 doses (RP2D) of 10 mg daily on Days 1 to 5 of each week, in a dose expansion, based upon the results from the Phase 1 portion of Part F.

Group V: Part E: mCRPC- KPT-8602 with abiraterone and corticosteroids Experimental Treatment 1 Intervention

Participants were treated with KPT-8602 at a dose and schedule that had been cleared in Part A in combination with abiraterone and corticosteroids. Participants continued to receive the dose and schedule of abiraterone and corticosteroids that they were receiving at the time of enrollment (completed).

Group VI: Part D: mCRPC- KPT-8602 single agent Experimental Treatment 1 Intervention

Participants were treated with KPT-8602 at a dose and schedule that has been cleared in Part A (completed).

Group VII: Part C: CRC- KPT-8602 single agent Experimental Treatment 1 Intervention

Participants were treated with KPT-8602 at a dose and schedule that has been cleared in Part A (completed).

Group VIII: Part B: RRMM- KPT-8602 with low-dose dexamethasone; QDx5/week Experimental Treatment 2 Interventions

Participants received KPT-8602 for 5 consecutive days (QDx5/week) in combination with low dose dexamethasone (20 milligram \[mg\] on Days 1, 3, 8, 10, 15, 17, 22, and 24 of each 28-day cycle) (completed).

Group IX: Part A2: RRMM- KPT-8602 single agent; QoDx3/week Experimental Treatment 1 Intervention

Participants received KPT-8602 once daily for 3 days per week (QoDx3/week). The starting dose for Part A2 will be informed by Part A1 (completed).

Group X: Part A1: RRMM- KPT-8602 single agent; QoDx5/week Experimental Treatment 1 Intervention

Participants received KPT-8602 once daily for 5 days per week (QDx5/week) at escalated doses (completed).

Who Is Running the Clinical Trial?

Karyopharm Therapeutics Inc

Lead 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

Citations

1. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/2997/423507/Eltanexor-KPT-8602-a-Second-Generation-Selective

Eltanexor (KPT-8602), a Second-Generation Selective ... Eltanexor (elta), a second-generation SINE compound, has demonstrated reduced brain penetration and improved tolerability compared to selinexor ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119836509

Eltanexor (KPT-8602), a Second-Generation Selective ... Results - As of 31-July-2017, 36 pts (23 M/13 F; median prior therapies: 7; median age: 66) with RRMM were enrolled; most with quad- or penta- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02649790

NCT02649790 | Study of the Safety, Tolerability and ... This is a first-in-human, multi-center, open-label clinical study with separate dose escalation (Phase 1) and expansion (Phase 2) stages to assess preliminary ...

4. investors.karyopharm.com investors.karyopharm.com/2017-12-10-Karyopharm-Presents-Positive-Phase-1-2-Eltanexor-Data-at-the-American-Society-of-Hematology-2017-Annual-Meeting

Karyopharm Presents Positive Phase 1/2 Eltanexor Data at ... − Preliminary Data Show that Eltanexor is Well Tolerated and Demonstrates Promising Activity in Multiple Myeloma —. − Expanding Program to ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5220128/

KPT-8602, a second-generation inhibitor of XPO1-mediated ... KPT-8602, a second-generation inhibitor of XPO1-mediated nuclear export, is well tolerated and highly active against AML blasts and leukemia-initiating cells.

6. medchemexpress.com medchemexpress.com/KPT-8602.html?srsltid=AfmBOoqGw_w-VvxQSkYfCIuWplmYgF3aRbqHR6XHa_zWMePUoEtoGkFm

Eltanexor (KPT-8602) | XPO1 Inhibitor | MedChemExpress The second-generation exportin-1 inhibitor KPT-8602 demonstrates potent activity against acute lymphoblastic leukemia. ... SAFETY DATA SHEET (SDS). English ...

7. caymanchem.com caymanchem.com/product/43585/eltanexor?srsltid=AfmBOooakseNoTveiVANEvO6_F8WXBpbr_uyTwM9_JfF4HjUfvTurg5J

Eltanexor (KPT-8602, CAS Number: 1642300-52-4) Eltanexor. Item No. 43585. Eltanexor (KPT-8602, CAS Number: 1642300-52-4). Download Product Insert (PDF)Download Safety Data Sheet (SDS) (PDF) ... acute myeloid ...

8. investors.karyopharm.com investors.karyopharm.com/2020-06-12-Karyopharm-Presents-XPOVIO-R-selinexor-and-Eltanexor-Data-at-the-European-Hematology-Association-2020-Virtual-Annual-Meeting

Karyopharm Presents XPOVIO® (selinexor) and Eltanexor ... The six selinexor abstracts include: (i) overall survival data from the Phase 2b SADAL study evaluating selinexor in patients with relapsed or ...