KPT-8602 for Multiple Myeloma

Recruiting at 44 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

277 Participants Needed

Trial Summary

What is the purpose of this trial?

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 safety, tolerability, and efficacy of the second generation oral XPO1 inhibitor KPT-8602 in participants with relapsed/refractory multiple myeloma (MM), metastatic colorectal cancer (mCRC), metastatic castration resistant prostate cancer (mCRPC), higher risk myelodysplastic syndrome (HRMDS), acute myeloid leukemia (AML) and newly diagnosed intermediate/high-risk MDS. Dose escalation and dose expansion may be included for all parts of the study as determined by ongoing study results.

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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