Study of the Safety, Tolerability and Efficacy of KPT-8602 in Participants with Relapsed/Refractory Cancer Indications
Phase 1
Completed
- Conditions
- Relapsed/Refractory Multiple Myeloma (RRMM)Metastatic Colorectal Cancer (mCRC)Metastatic Castration-Resistant Prostate Cancer (mCRPC)Higher-Risk Myelodysplastic Syndrome (HR-MDS)Newly Diagnosed Intermediate/High-Risk MDSAcute Myeloid Leukemia (AML)
- Interventions
- Registration Number
- NCT02649790
- Lead Sponsor
- Karyopharm Therapeutics Inc
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 277
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part C: CRC- KPT-8602 single agent KPT-8602 Participants were treated with KPT-8602 at a dose and schedule that has been cleared in Part A (completed). Part B: RRMM- KPT-8602 with low-dose dexamethasone; QDx5/week KPT-8602 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). Part D: mCRPC- KPT-8602 single agent KPT-8602 Participants were treated with KPT-8602 at a dose and schedule that has been cleared in Part A (completed). Part E: mCRPC- KPT-8602 with abiraterone and corticosteroids KPT-8602 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). Part G: Newly Diagnosed Intermediate/High-Risk MDS -KPT-8602 with ASTX727 ASTX727 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. Part H: AML Maintenance Therapy- KPT-8602 single agent KPT-8602 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. Part A1: RRMM- KPT-8602 single agent; QoDx5/week KPT-8602 Participants received KPT-8602 once daily for 5 days per week (QDx5/week) at escalated doses (completed). Part A2: RRMM- KPT-8602 single agent; QoDx3/week KPT-8602 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). Part F: High-risk Myelodysplastic Syndrome (MDS)- KPT-8602 single agent KPT-8602 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). Part F Phase 2: RR High-risk MDS- KPT-8602 single agent KPT-8602 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. Part G: Newly Diagnosed Intermediate/High-Risk MDS -KPT-8602 with ASTX727 KPT-8602 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. Part B: RRMM- KPT-8602 with low-dose dexamethasone; QDx5/week Dexamethasone 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).
- Primary Outcome Measures
Name Time Method Part A1, A2, B, C, D, E, F: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) Approximately 4 weeks Part A1, A2, B, C, D, E, F: Overall Response Rate (ORR) Approximately 8 years Part A1, A2, B, C, D, E, F: Clinical Benefit Rate (CBR) Approximately 8 years Part A1, A2, B, C, D, E, F: Duration of Response (DOR) Approximately 8 years Part A1, A2, B, C, D, E, F: Progression-free Survival (PFS) Approximately 8 years Part A1, A2, B, C, D, E, F: Overall Survival (OS) Approximately 8 years Part A1, A2, B, C, D, E, F: Duration of Clinical Benefit Rate (CBR) Approximately 8 years Part A1, A2, B, C, D, E, F: Disease Control Rate (DCR) Approximately 8 years Part A1, A2, B, C, D, E, F: Duration of DCR Approximately 8 years Part F Phase 2: ORR Approximately 8 years Part G: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) Approximately 8 years Part H: 2- Year Progression-free Survival (PFS) Approximately Up to 2 years
- Secondary Outcome Measures
Name Time Method Part A1, A2, B, C, D, E, F, H: Area Under the Plasma Concentration Time Curve from Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Eltanexor Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years Part A1, A2, B, C, D, E, F, H: Maximum Observed Plasma Concentration (Cmax) of Eltanexor Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years Part A1, A2, B, C, D, E, F, H: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Eltanexor Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years Part A1, A2, B, C, D, E, F, H: Apparent Terminal Half Life (t1/2) of Eltanexor Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years Part A1, A2, B, C, D, E, F, H: Apparent Total Body Clearance Eltanexor Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years Part A1, A2, B, C, D, E, F, H: Apparent Volume of Distribution During Terminal Phase (VZ/f) of Eltanexor Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years Part F Phase 2: Overall Survival (OS) Approximately 8 years Part F Phase 2: 6-Month Overall Survival (OS) Approximately Up to 6 Months Part F Phase 2: Progression-free Survival (PFS) Approximately 8 years Part F Phase 2: Disease Control Rate (DCR) Approximately 8 years Part F Phase 2: Duration of Response (DOR) Approximately 8 years Part F Phase 2: Rate of Conversion from Red Blood Cell (RBC) Transfusion Dependence to Independence Approximately 8 years Part F Phase 2: Rate of Conversion from Platelet Transfusion Dependence to Independence Approximately 8 years Part G: Overall Response Rate (ORR) Approximately 8 years Part G: Duration of Response (DOR) Approximately 8 years Part H: Rate of Minimal Residual Disease (MRD) Conversion from Positive to Negative Approximately 8 years Part H: Time to Minimal Residual Disease (MRD) Negativity Approximately 8 years Part H: Percentage of Participants with Acute and Chronic Graft-versus-Host Disease (GVHD) Approximately 8 years Part H: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) Approximately 8 years Part H: Overall Survival (OS) Approximately 8 years
Trial Locations
- Locations (46)
David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
Oncology Institute of Hope and Innovation
🇺🇸Pasadena, California, United States
Rocky Mountain Regional VA Medical Center
🇺🇸Aurora, Colorado, United States
Sarah Cannon Cancer Center - (Colorado Blood Cancer Institute)
🇺🇸Denver, Colorado, United States
(USO) Rocky Mountain Cancer Centers
🇺🇸Littleton, Colorado, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Cancer and Hematology Centers of Western Michigan
🇺🇸Grand Rapids, Michigan, United States
Sarah Cannon Cancer Center (HCA Midwest KC)
🇺🇸Kansas City, Missouri, United States
Callahan Cancer Center
🇺🇸North Platte, Nebraska, United States
John Theurer Cancer Center at Hackensack UMC
🇺🇸Hackensack, New Jersey, United States
Scroll for more (36 remaining)David Geffen School of Medicine at UCLA🇺🇸Los Angeles, California, United States