Study of the Safety, Tolerability and Efficacy of KPT-8602 in Participants With Relapsed/Refractory Cancer Indications

• ClinicalTrials.gov Identifier: NCT02649790
• Recruitment Status: Recruiting
• First Posted: January 7, 2016
• Last Update Posted: May 3, 2022
• Sponsor: Karyopharm Therapeutics Inc
• Information provided by (Responsible Party): Karyopharm Therapeutics Inc

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Relapsed/Refractory Multiple Myeloma (RRMM); Metastatic Colorectal Cancer (mCRC); Metastatic Castration Resistant Prostate Cancer (mCRPC); Higher Risk Myelodysplastic Syndrome (HR-MDS); Acute Myeloid Leukemia (AML); Newly Diagnosed Intermediate/High-Risk MDS	Drug: KPT-8602; Drug: ASTX727; Drug: Dexamethasone	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 119 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Open-Label Study of the Safety, Tolerability and Efficacy of the Selective Inhibitor of Nuclear Export (SINE) Compound Eltanexor (KPT-8602) in Patients With Newly Diagnosed and Relapsed/Refractory Cancer Indications
• Actual Study Start Date: January 2016
• Estimated Primary Completion Date: August 31, 2024
• Estimated Study Completion Date: August 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part A1: RRMM- KPT-8602 single agent; QoDx5/week; Participants received KPT-8602 once daily for 5 days per week (QDx5/week) at escalated doses (completed).	Drug: KPT-8602; Participants will receive KPT-8602 oral tablets.
Experimental: Part A2: RRMM- KPT-8602 single agent; QoDx3/week; 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).	Drug: KPT-8602; Participants will receive KPT-8602 oral tablets.
Experimental: Part B: RRMM- KPT-8602 with low-dose dexamethasone; QDx5/week; 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).	Drug: KPT-8602; Participants will receive KPT-8602 oral tablets.; Drug: Dexamethasone; Participants will receive dexamethasone oral tablets.
Experimental: Part C: RRCRC- KPT-8602 single agent; Participants were treated with KPT-8602 at a dose and schedule that has been cleared in Part A (completed).	Drug: KPT-8602; Participants will receive KPT-8602 oral tablets.
Experimental: Part D: RRmCRPC- KPT-8602 single agent; Participants were treated with KPT-8602 at a dose and schedule that has been cleared in Part A (completed).	Drug: KPT-8602; Participants will receive KPT-8602 oral tablets.
Experimental: Part E: RRmCRPC- KPT-8602 with abiraterone and corticosteroids; 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).	Drug: KPT-8602; Participants will receive KPT-8602 oral tablets.
Experimental: Part F: High-risk Myelodysplastic Syndrome (MDS)- KPT-8602 single agent; 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).	Drug: KPT-8602; Participants will receive KPT-8602 oral tablets.
Experimental: Part F Phase 2: High-risk MDS- KPT-8602 single agent; 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.	Drug: KPT-8602; Participants will receive KPT-8602 oral tablets.
Experimental: Part G: Newly Diagnosed Intermediate/High-Risk MDS -KPT-8602 with 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.	Drug: KPT-8602; Participants will receive KPT-8602 oral tablets.; Drug: ASTX727; ASTX727 is a combination drug of 35 mg decitabine and 100 mg cedazuridine.
Experimental: Part H: AML Maintenance Therapy- KPT-8602 single agent; 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.	Drug: KPT-8602; Participants will receive KPT-8602 oral tablets.

Outcome Measures

Primary Outcome Measures :

1. Part A1, A2, B, C, D, E, F: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) [ Time Frame: Approximately 4 weeks ]
2. Part A1, A2, B, C, D, E, F: Overall Response Rate (ORR) [ Time Frame: Approximately 8 years ]
3. Part A1, A2, B, C, D, E, F: Duration of Response (DOR) [ Time Frame: Approximately 8 years ]
4. Part A1, A2, B, C, D, E, F: Progression-free survival (PFS) [ Time Frame: Approximately 8 years ]
5. Part A1, A2, B, C, D, E, F: Overall Survival (OS) [ Time Frame: Approximately 8 years ]
6. Part A1, A2, B, C, D, E, F: Clinical Benefit Rate (CBR) [ Time Frame: Approximately 8 years ]
7. Part A1, A2, B, C, D, E, F: Duration of Clinical Benefit Rate (CBR) [ Time Frame: Approximately 8 years ]
8. Part A1, A2, B, C, D, E, F: Disease control rate (DCR) [ Time Frame: Approximately 8 years ]
9. Part A1, A2, B, C, D, E, F: Duration of DCR [ Time Frame: Approximately 8 years ]
10. Part F Phase 2: ORR [ Time Frame: Approximately 8 years ]
11. Part G: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) [ Time Frame: Approximately 8 years ]
12. Part H: 2- Year Progression-free Survival (PFS) [ Time Frame: Approximately Up to 2 years ]

Secondary Outcome Measures :

1. 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 [ Time Frame: Pre-dose 2 hours post-dose Cycle1Day1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle1Day21 and 26; 24 hours post-dose Cycle1Day2, 22,and 27; 48 hours post-dose Cycle1Day23 and 28 and up to approximately 8 years ]
2. Part A1, A2, B, C, D, E, F, H: Maximum Observed Plasma Concentration (Cmax) of Eltanexor [ Time Frame: Pre-dose 2 hours post-dose Cycle1Day1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle1Day21 and 26; 24 hours post-dose Cycle1Day2, 22,and 27; 48 hours post-dose Cycle1Day23 and 28 and up to approximately 8 years ]
3. Part A1, A2, B, C, D, E, F, H: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Eltanexor [ Time Frame: Pre-dose 2 hours post-dose Cycle1Day1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle1Day21 and 26; 24 hours post-dose Cycle1Day2, 22,and 27; 48 hours post-dose Cycle1Day23 and 28 and up to approximately 8 years ]
4. Part A1, A2, B, C, D, E, F, H: Apparent Terminal Half Life (t1/2) of Eltanexor [ Time Frame: Pre-dose 2 hours post-dose Cycle1Day1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle1Day21 and 26; 24 hours post-dose Cycle1Day2, 22,and 27; 48 hours post-dose Cycle1Day23 and 28 and up to approximately 8 years ]
5. Part A1, A2, B, C, D, E, F, H: Apparent Total Body Clearance Eltanexor [ Time Frame: Pre-dose 2 hours post-dose Cycle1Day1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle1Day21 and 26; 24 hours post-dose Cycle1Day2, 22,and 27; 48 hours post-dose Cycle1Day23 and 28 and up to approximately 8 years ]
6. Part A1, A2, B, C, D, E, F, H: Apparent Volume of Distribution During Terminal Phase (VZ/f) of Eltanexor [ Time Frame: Pre-dose 2 hours post-dose Cycle1Day1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle1Day21 and 26; 24 hours post-dose Cycle1Day2, 22,and 27; 48 hours post-dose Cycle1Day23 and 28 and up to approximately 8 years ]
7. Part F Phase 2: Overall Survival (OS) [ Time Frame: Approximately 8 years ]
8. Part F Phase 2: 6-Month Overall Survival (OS) [ Time Frame: Approximately Up to 6 Months ]
9. Part F Phase 2: Progression-free survival (PFS) [ Time Frame: Approximately 8 years ]
10. Part F Phase 2: Disease control rate (DCR) [ Time Frame: Approximately 8 years ]
11. Part F Phase 2: Duration of Response (DOR) [ Time Frame: Approximately 8 years ]
12. Part F Phase 2: Rate of Conversion from Red Blood Cell (RBC) Transfusion Dependence to Independence [ Time Frame: Approximately 8 years ]
13. Part F Phase 2: Rate of Conversion from Platelet Transfusion Dependence to Independence [ Time Frame: Approximately 8 years ]
14. Part G: Overall Response Rate (ORR) [ Time Frame: Approximately 8 years ]
15. Part G: Duration of Response (DOR) [ Time Frame: Approximately 8 years ]
16. Part H: Rate of Minimal Residual Disease (MRD) Conversion from Positive to Negative [ Time Frame: Approximately 8 years ]
17. Part H: Time to Minimal Residual Disease (MRD) Negativity [ Time Frame: Approximately 8 years ]
18. Part H: Percentage of Participants with Acute and Chronic Graft-versus-Host Disease (GVHD) [ Time Frame: Approximately 8 years ]
19. Part H: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Approximately 8 years ]
20. Part H: Overall Survival (OS) [ Time Frame: Approximately 8 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

INCLUSION CRITERIA

1. Written informed consent signed prior to any screening procedures and in accordance with federal, local, and institutional guidelines.
2. Age ≥18 years.

3. Adequate hepatic function:

   1. total bilirubin ≤2 times the upper limit of normal (ULN) (except participants with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤4 times ULN),
   2. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times ULN (except participants with known liver involvement of their tumor who must have their AST and ALT ≤5.0 times ULN).
4. Adequate renal function: estimated creatinine clearance of ≥30 mL/min, calculated using the formula of Cockcroft and Gault (140-Age) × Mass (kg)/(72 × creatinine mg/dL); multiply by 0.85 if female.

5. Contraception:

   1. Participants with RRMM, CRC, RR high-risk MDS (Part F Phase 2), and AML (Part H): Female participants of child-bearing potential must agree to use dual methods of contraception (including 1 highly effective and 1 effective method of contraception) and have a negative serum test at Screening, and male participants must use an effective barrier method of contraception if sexually active. For both male and female participants, effective methods of contraception must be used throughout the study and for 3 months following the last dose.
   2. Participants with RR mCRPC: Participants must use an effective barrier method of contraception if sexually active. Effective methods of contraception must be used throughout the study and for 3 months following the last dose.
   3. Participants with newly diagnosed intermediate/high-risk MDS (Part G): Female participants of child-bearing potential must agree to use dual methods of contraception (including 1 highly effective and 1 effective method of contraception) and have a negative serum pregnancy test at Screening, and male participants must use an effective barrier method of contraception if sexually active. For both male and female participants, effective methods of contraception must be used throughout the study and for 6 months following the last dose.

   INDICATION-SPECIFIC INCLUSION CRITERIA

   Relapsed/Refractory Multiple Myeloma (Parts A1, A2, and B - Completed):

6. Symptomatic, histologically confirmed MM and evidence of disease progression, based on IMWG guidelines.

7. Participants must have measurable disease as defined by at least 1 of the following:

   1. Serum M-protein ≥0.5 g/dL by serum protein electrophoresis (SPEP) or for immunoglobulin (Ig) A myeloma, by quantitative IgA. If SPEP is felt to be unreliable for routine M-protein measurement (e.g., for participants with IgA MM), then quantitative Ig levels by nephelometry; or
   2. Urinary M-protein excretion at least 200 mg/24 hours; or
   3. Serum free light chain (FLC) whereby the involved light chain measures ≥10 mg/dL and with an abnormal ratio.
8. Previously treated with ≥3 prior regimens (lines of therapy) that included at least 1 of each of the following: an immunomodulatory drug, a proteasome inhibitor, and a steroid.
9. MM refractory to the participants most recent anti-MM regimen.
10. Participants receiving hematopoietic growth factor support including erythropoietin, darbepoetin, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, and platelet stimulators can continue to do so, but must be transfusion independent for at least 1 week prior to Cycle 1 Day 1 (C1D1) in the study.
11. Adequate hematopoietic function: total white blood cell (WBC) count ≥1500/mm^3, absolute neutrophil count (ANC) ≥800/mm^3, hemoglobin (Hb) ≥8.0 g/dL, and platelet count ≥75,000/mm^3.
12. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.

13. Life expectancy of ≥4 months.

    Relapsed/Refractory Colorectal Cancer (Part C - Completed):

14. Histological or cytological documentation of adenocarcinoma of the colon or rectum.
15. Measurable disease by RECIST v1.1.
16. Metastatic disease not suitable for upfront curative-intent surgery.
17. Participants with site-defined KRAS status (wild-type or mutant) from a fresh or archival tumor biopsy prior to enrollment. All participants must be willing to have fresh biopsies to obtain tumor tissue for biomarker analysis.
18. Documented evidence of progressive disease according to RECIST v1.1.

19. Prior treatment (with completion of a course of therapy, or to disease progression or intolerability) with each of the following:

    1. Fluoropyrimidine-, oxaliplatin-, irinotecan-based chemotherapies (e.g., FOLFOX and/or FOLFIRI)
    2. if KRAS wild-type, an anti-EGFR therapy,
    3. Prior third line treatment with regorafenib or TAS-102, will be assessed on an individual basis,
    4. Note: The requirement for prior third line regorafenib will be assessed on an individual basis by the investigator in consultation with the Karyopharm Medical Monitor
    5. Radiation and surgery are not considered as prior anticancer regimens
20. Participants should not be transfusion dependent.
21. Adequate hematopoietic function: ANC ≥1000/mm^3, hemoglobin (Hb) ≥9.0 g/dL, and platelet count ≥100,000/mm^3.
22. ECOG performance status of ≤1.

23. Life expectancy of ≥4 months.

    Relapsed/Refractory Metastatic Castration-resistant Prostate Cancer (Parts D and E - Completed):

24. Histologically confirmed adenocarcinoma of the prostate with archival tumor tissue available for molecular analyses. If the participants does not have a prior histological diagnosis, then a fresh biopsy at Screening may be used for this purpose.

    a. Optional: All participants will be asked to have fresh biopsies to obtain tumor tissue for biomarker analysis.

25. Surgically or medically castrated, with testosterone levels of <50 ng/dL (<2.0 nM). If the participant is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (participants who have not undergone orchiectomy), and participants must have shown to progress on this.

26. Documented mCRPC progression as assessed by the Investigator with 1 of the following:

    1. Prostate-specific antigen (PSA) progression defined by a minimum of 3 rising PSA levels (at approximately Day -30 and approximately Day -45) with an interval of >1 week between each determination. The PSA values at the Screening visit should be >2 μg/L (>2 ng/mL); participants on systemic glucocorticoids for control of symptoms must have documented PSA progression by Prostate Cancer Working Group 3 (PCWG3) while on systemic glucocorticoids prior to commencing C1D1 of treatment.
    2. Radiographic progression of soft tissue disease by modified RECIST criteria 1.1 or of bone metastasis with 2 or more documented new bone lesions on a bone scan with or without PSA progression.
27. Initial response (per modified PCWG3 Guidelines) to second generation anti-hormonal therapy (examples: abiraterone, enzalutamide, TAK 700), but later relapsed. Disease relapse would be defined as progressive disease at the time of entry per inclusion criterion 24.
28. Zero to 2 previous taxane-based chemotherapy regimens. If docetaxel chemotherapy is used more than once, this will be considered as 1 regimen. Participants may have had prior exposure to cabazitaxel treatment. Participants may be taxane naïve.
29. At least 2 weeks from completion of any radiotherapy including a single fraction of radiotherapy for the purposes of palliation (confined to 1 field) is permitted.
30. Participants should not be transfusion dependent.
31. Albumin >2.5 g/dL.
32. Adequate hematopoietic function: ANC ≥1000/mm^3, hemoglobin (Hb) ≥9.0 g/dL, and platelet count ≥100,000/mm^3.
33. Part E only: Participants currently receiving treatment with abiraterone and appropriate to continue in the opinion of the Investigator. Participants must also have been on and continue on a stable dose of corticosteroids (prednisone or dexamethasone) for 30 days prior to C1D1.
34. ECOG performance status of ≤1.

35. Life expectancy of ≥4 months.

    RR High-risk Myelodysplastic Syndrome (Part F Phase 2):

36. Documented diagnosis of MDS with 5% to 19% myeloblasts in the bone marrow (2016 WHO classification)
37. The marrow histopathology must be documented by recent bone marrow biopsy
38. Participants should be intermediate, high- or very-high-risk MDS by IPSS-R

39. Participants with HMA (primary)-refractory MDS, including:

    1. ≥2 cycles of hypomethylating agents (azacitidine and/or decitabine, ASTX727, or experimental agents) with clear progressive disease (PD) (pancytopenia, with ≥50% increase in bone marrow blasts) or participants progressed to a higher-risk category of MDS OR
    2. ≥4 cycles of azacitidine and/or decitabine (or other hypomethylating therapy) with SD/lack of improvement (no CR/mCR/PR/HI) per IWG criteria
40. ECOG performance status of <2

41. Prior to enrolling a participant with imminent risk of AML transformation (per opinion of the Investigator) or for participants with RAEB-2 MDS, the Medical Monitor must be contacted

    Newly Diagnosed Intermediate/High-risk Myelodysplastic Syndrome (Part G):

42. Documented diagnosis of MDS with 5% to 19% myeloblasts in the bone marrow (2016 WHO classification)

    • The marrow histopathology must be documented in bone marrow biopsy
    • Participants should be intermediate, high- or very high-risk MDS by IPSS-R
43. No prior therapy for MDS. (One prior cycle of a hypomethylating agent is allowed, but no other cytotoxic chemotherapy is permitted within 2 weeks of starting study treatment.)

44. ECOG performance status of <2

    AML Maintenance (Post-alloSCT) Therapy (Part H):

45. Participants with de novo AML or AML secondary to prior myelodysplastic disease
46. Received an allogeneic SCT
47. At the time of allogeneic SCT, no prior allogeneic HSCT
48. Participants must be able to start study treatment between 40 and 100 days following alloSCT

49. Participants with CR/CRi status confirmed prior to alloSCT according to the following criteria, must also be MRD-positive by multi-parameter flow cytometry (MFC) at either pre-allo or at time of enrollment:

    Complete remission:

    • <5% blasts in bone marrow
    • Absence of blasts with Auer rods
    • Absence of extramedullary disease
    • Independent of blood transfusions
    • Peripheral neutrophil count ≥1.0 x 10^9/L
    • Platelet count ≥100 x 10^9/L

    Complete remission with incomplete blood count recovery:

    • <5% blasts in bone marrow
    • Absence of blasts with Auer rods
    • Absence of extramedullary disease
    • Independent of blood transfusions
    • Peripheral neutrophil count <1.0 x 10^9/L, or
    • Platelet count <100 x 10^9/L

50. If not in CR/CRi with MRD positivity prior to alloSCT, may have any of the following high-risk features:

    • Relapsed AML, not in CR
    • If CR2 or greater, may enroll regardless of disease characteristics at initial diagnosis
    • High-risk cytogenetics at time of diagnosis
51. Adequate engraftment within 14 days prior to starting study therapy: ANC ≥1.0 x 10^9/L without daily use of myeloid growth factor, and platelet count 75 x 10^9/L without platelet transfusion within 1 week
52. ECOG performance status of ≤2

EXCLUSION CRITERIA

Participants in All Parts of the Study:

1. Female participants who are pregnant or lactating
2. Major surgery within 4 weeks before C1D1

3. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

   1. Unstable angina or acute myocardial infarction ≤3 months prior to C1D1
   2. Clinically significant heart disease (e.g., symptomatic congestive heart failure [e.g., >NYHA Class 2]; uncontrolled arrhythmia, or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
4. Uncontrolled active severe systemic infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1
5. Participants with known symptomatic brain metastasis are not suitable for enrollment. Participants with asymptomatic, stable, treated brain metastases are eligible for study entry
6. Participants with a known history of human immunodeficiency virus (HIV); HIV testing is not required as part of this study
7. Known, active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen)

8. Prior malignancies:

   1. Participants with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (i.e., cervix) may enroll irrespective of the time of diagnosis
   2. Participants with relapsed/refractory MM, CRC, and mCRPC only: Prior malignancies which may interfere with the interpretation of the study. Cancer treated with curative intent <5 years previously will not be allowed unless approved by the Sponsor. Cancer treated with curative intent >5 years previously and without evidence of recurrence will be allowed.
   3. For participants in Arms F Phase 2, G, and H: Prior malignancy is not an exclusion
9. Participants with gastrointestinal tract disease (or uncontrolled vomiting or diarrhea) that could interfere with the absorption of eltanexor (or ASTX727 in Part G)
10. Serious psychiatric or medical conditions that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give consent

11. Participants unwilling to comply with the protocol including required biopsies and sample collections required to measure disease

    INDICATION-SPECIFIC EXCLUSION CRITERIA

    Relapsed/Refractory Multiple Myeloma (RRMM) (Parts A1, A2 and B - Completed):

12. Time since the last prior therapy for treatment of RRMM:

    1. Radiation, chemotherapy, immunotherapy or any other anticancer therapy, including investigational anticancer therapy ≤2 weeks prior to C1D1
    2. Palliative steroids for disease related symptoms are allowed up to 3 days prior to C1D1.
    3. Participants must have recovered or stabilized (≤Grade 1 or to their baseline) from toxicities related to their previous treatment except for alopecia
13. Participants with active graft versus host disease after allogeneic stem cell transplantation. At least 3 months must have elapsed since completion of allogeneic stem cell transplantation

14. Grade >2 peripheral neuropathy or Grade 2 peripheral neuropathy with pain within 2 weeks prior to C1D1

    Relapsed/Refractory Colorectal Cancer (Part C - Completed):

15. Radiotherapy, chemotherapy, or any other anticancer therapy, including investigational anticancer therapy within 2 weeks prior to Screening. Participants must have recovered from clinically significant toxicities. The site of irradiation should have evidence of progressive disease (new lesions or increase in lesion size) if this is the only site of disease

16. Participants who have been treated with their most recent chemotherapy or investigational drugs ≤21 days or 5 half-lives (whichever is longer) prior to the first dose of study treatment, and/or have any acute toxicities due to prior chemotherapy and/ or radiotherapy that have not resolved to a NCI CTCAE v4.03 Grade 0 or Grade 1 with the exception of chemotherapy induced alopecia and Grade 2 peripheral neuropathy

    Relapsed/Refractory Metastatic Castration-Resistant Prostate Cancer (Parts D and E - Completed):

17. Participants who have been treated with their most recent chemotherapy or investigational drugs ≤21 days or 5 half-lives (whichever is longer) prior to the first dose of study treatment, and/or have any acute toxicities due to prior chemotherapy and/ or radiotherapy that have not resolved to a NCI CTCAE v4.03 Grade 0 or Grade 1 with the exception of chemotherapy-induced alopecia and Grade 2 peripheral neuropathy

18. Initiating bisphosphonate therapy or adjusting bisphosphonate dose/regimen within 30 days prior to C1D1. Participants on a stable bisphosphonate or denosumab regimen are eligible and may continue

    RR High-risk Myelodysplastic Syndrome (Part F Phase 2):

19. IPSS-R very low or low-risk MDS
20. Evidence of transformation to AML by the World Health Organization (WHO) (≥20% blasts in bone marrow or peripheral blood)

21. Participants who demonstrate doubling of their bone marrow blast percentage within 4 weeks prior to Screening and have absolute blast percentage of > 15% at the time of Screening

    Newly Diagnosed Intermediate/High-risk Myelodysplastic Syndrome (Part G):

22. IPSS-R very low or low-risk MDS

23. Evidence of transformation to AML by the WHO (≥20% blasts in bone marrow or peripheral blood)

    AML Maintenance (Post-alloSCT) Therapy (Part H):

24. Use of any of the following after transplantation and prior to starting study treatment: chemotherapeutic agents for chemotherapy; investigational agents/therapies; azacitidine, decitabine or other demethylating agents; or lenalidomide, thalidomide, or pomalidomide
25. Active GVHD Grade 2 or higher
26. Concurrent use of corticosteroids equivalent of prednisone at a dose >0.5 mg/kg

Contacts and Locations

Contacts

Contact: Eric Sbar VP of Clinical Development, DO; eric.sbar@karyopharm.com

Contact: Sharon Shacham, PhD

Locations

United States, California

Oncology Institute of Hope and Innovation; Not yet recruiting

Pasadena, California, United States, 91105

Contact: Amitabha Mazumder, MD 626-486-9447 AmitabhaMazumder@theoncologyinstitute.com

Principal Investigator: Amitabha Mazumder, MD

United States, Colorado

Sarah Cannon Cancer Center - (Colorado Blood Cancer Institute); Recruiting

Denver, Colorado, United States, 80218

Contact: Alexandra Mandy 720-754-8065 Alexandra.Mandy@SarahCannon.com

Principal Investigator: Luke Mountjoy, MD

(USO) Rocky Mountain Cancer Centers; Recruiting

Littleton, Colorado, United States, 80120-4413

Contact: Christopher Benton, MD 303-730-4700 christopher.benton@usoncology.com

Principal Investigator: Christopher Benton, MD

United States, Florida

Moffitt Cancer Center; Completed

Tampa, Florida, United States, 33612

United States, Michigan

Cancer and Hematology Centers of Western Michigan; Recruiting

Grand Rapids, Michigan, United States, 49503

Contact: Shannon Fabrie 616-954-5550 sfabrie@chcwm.com

Principal Investigator: Brett Brinker, MD

United States, Missouri

Sarah Cannon Cancer Center (HCA Midwest KC); Recruiting

Kansas City, Missouri, United States, 64132

Contact: Chris Baierl 816-276-9156 christopher.baierl@hcamidwest.com

Principal Investigator: Suman Kambhampati, MD

United States, New Jersey

John Theurer Cancer Center at Hackensack UMC; Completed

Hackensack, New Jersey, United States, 07601

United States, New Mexico

University of New Mexico; Recruiting

Albuquerque, New Mexico, United States, 87131

Contact: Ala Ebaid, MD 505-272-4946 aebaid@salud.unm.edu

Principal Investigator: Ala Ebaid, MD

United States, New York

Weill Cornell Medical College; Recruiting

New York, New York, United States, 10021

Contact: Sangmin Lee, MD 646-962-7200 sal9053@med.cornell.edu

Principal Investigator: Sangmin Lee, MD

United States, Ohio

(USO) Oncology Hematology Care; Recruiting

Cincinnati, Ohio, United States, 45236

Contact: Edward Broun, MD 513-751-2273 randy.broun@usoncology.com

Principal Investigator: Edward Broun, MD

Ohio State University, The James Cancer Hospital and Solove Research Institute; Recruiting

Columbus, Ohio, United States, 43210

Contact: Kristen Koenig, MD Kristin.Koenig@osumc.edu

Principal Investigator: Kristen Koenig, MD

United States, Pennsylvania

University of Pennsylvania Abramson Cancer Center Clinical Research Unit; Completed

Philadelphia, Pennsylvania, United States, 19104

United States, Tennessee

Vanderbilt University Medical Center; Not yet recruiting

Nashville, Tennessee, United States, 37232

Contact: Sanjay Mohan, MD sanjay.mohan@vumc.org

Principal Investigator: Sanjay Mohan, MD

United States, Texas

(USO) Texas Oncology Austin - Midtown; Recruiting

Austin, Texas, United States, 78705

Contact: Jason Melear, MD jason.melear@usoncology.com

Principal Investigator: Jason Melear, MD

(USO) Texas Oncology (Dallas); Recruiting

Dallas, Texas, United States, 75246

Contact: Edward Pearson, MD 817-939-3733 edward.pearson1@usoncology.com

Principal Investigator: Edward Pearson, MD

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Guillermo Garcia-Manero, MD ggarciam@mdanderson.org

Principal Investigator: Guillermo Garcia-Manero, MD

(USO) Texas Oncology (Tyler); Recruiting

Tyler, Texas, United States, 75702

Contact: Habte Yimer, MD 903-579-9800 habte.yimer@usoncology.com

Principal Investigator: Habte Yimer, MD

United States, Virginia

University of Virginia; Recruiting

Charlottesville, Virginia, United States, 22903

Contact: Indumathy Varadarajan, MD 434-305-6983 IV8MM@virginia.edu

Principal Investigator: Indumathy Varadarajan, MD

(USO) Virginia Cancer Specialists; Recruiting

Fairfax, Virginia, United States, 22031

Contact: Mitul Gandhi, MD 703-280-5390 mitul.gandhi@usoncology.com

Principal Investigator: Mitul Gandhi, MD

United States, Washington

University of Washington; Recruiting

Seattle, Washington, United States, 98109

Contact: Anna Halpern, MD halpern2@uw.edu

Principal Investigator: Anna Halpern, MD

(USO) Compass oncology; Recruiting

Vancouver, Washington, United States, 98684

Contact: Anthony Van Ho, MD anthony.vanho@compassoncology.com

Principal Investigator: Anthony Van Ho, MD

Canada, Ontario

McMaster - Juravinski Cancer Centre; Recruiting

Hamilton, Ontario, Canada

Contact: Dina Khalaf, MD khalaf@hhsc.ca

Principal Investigator: Dina Khalaf, MD

Princess Margaret Cancer Center; Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contact: Karen Yee, MD 416 946 4495 karen.yee@uhn.ca

Principal Investigator: Karen Yee, MD

Princess Margaret Cancer Research; Completed

Toronto, Ontario, Canada

Canada, Quebec

MUHC GLEN Site Cedars - Cancer Centre; Completed

Montréal, Quebec, Canada

France

CHU Nantes; Recruiting

Nantes, France, 44000

Contact: Alice Garnier, MD 33232282589 alice.garnier@chu-nantes.fr

Principal Investigator: Alice Garnier, MD

Hôpital Cochin APHP; Recruiting

Paris, France, 75014

Contact: Lise Willems, MD +331.58.41.26.70 lise.willems@aphp.fr

Principal Investigator: Lise Willems, MD

Hôpital St Louis; Recruiting

Paris, France

Contact: Pierre Fenaux, MD 608067570 pierre.fenaux@aphp.fr

Principal Investigator: Pierre Fenaux, MD

CHU de Bordeaux; Recruiting

Pessac, France, 33604

Contact: Sophie Dimicoli-Salazar, MD +33 (0)5 57 65 65 11 sophie.dimicoli-salazar@chu-bordeaux.fr

Principal Investigator: Sophie Dimicoli-Salazar, MD

CHU de Tours; Recruiting

Tours, France, 37044

Contact: Emmanuel Gyan, MD 33247473712 emmanuel.gyan@univ-tours.fr

Principal Investigator: Emmanuel Gyan, MD

Spain

Hospital San Pedro de Alcántara; Recruiting

Cáceres, Spain

Contact: Juan Miguel Bergua, MD 34927621540 jmberguaburg@gmail.com

Principal Investigator: Juan Miguel Bergua, MD

Hospital La Fe; Recruiting

Valencia, Spain

Contact: Pau Montesinos, MD montesinos_pau@gva.es

Principal Investigator: Pau Montesinos, MD

Sponsors and Collaborators

Karyopharm Therapeutics Inc

Investigators

• Study Director: Eric Sbar VP of Clinical Development, DO; Karyopharm Therapeutics Inc

More Information

• Responsible Party: Karyopharm Therapeutics Inc
• ClinicalTrials.gov Identifier: NCT02649790
• Other Study ID Numbers: KCP-8602-801
• First Posted: January 7, 2016
• Last Update Posted: May 3, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Karyopharm Therapeutics Inc:

KPT-8602; Multiple Myeloma; Karyopharm; MM; Phase 1; Relapsed/ Refractory Multiple Myeloma; Myelodysplastic Syndrome; MDS; Metastatic Castration Resistant Prostate Cancer; mCRPC; CRC; Metastatic Colorectal Cancer; AML

Additional relevant MeSH terms:

Prostatic Neoplasms; Colorectal Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders