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

Completed · Phase 1/Phase 2

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT02649790

Run by

Karyopharm Therapeutics Inc

People needed

277

Starts

2016-01-01

Expected to finish

2024-12-23

Last updated by the study team

2025-03-19

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Written informed consent signed prior to any screening procedures and in accordance with federal, local, and institutional guidelines.
• Age ≥ 18 years.
• Adequate hepatic function:
• 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),
• 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).
• 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.
• Contraception:
• 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
• 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
• 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):
• Symptomatic, histologically confirmed MM and evidence of disease progression, based on IMWG guidelines.
• Participants must have measurable disease as defined by at least 1 of the following:
• 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
• Urinary M-protein excretion at least 200 mg/24 hours; or
• Serum free light chain (FLC) whereby the involved light chain measures ≥ 10 mg/dL and with an abnormal ratio.
• 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.
• MM refractory to the participants most recent anti-MM regimen.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
• Life expectancy of ≥ 4 months.
• Relapsed/Refractory Colorectal Cancer (Part C - Completed):
• Histological or cytological documentation of adenocarcinoma of the colon or rectum.

You may not qualify if…

• Participants in All Parts of the Study:
• Female participants who are pregnant or lactating.
• Major surgery within 4 weeks before C1D1.
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• Unstable angina or acute myocardial infarction ≤ 3 months prior to C1D1
• 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)
• Uncontrolled active severe systemic infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1.
• Participants with known symptomatic brain metastasis are not suitable for enrollment. Participants with asymptomatic, stable, treated brain metastases are eligible for study entry
• Participants with a known history of human immunodeficiency virus (HIV); HIV testing is not required as part of this study
• Known, active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen)
• Prior malignancies:
• 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
• 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.
• For participants in Arms F Phase 2, G, and H: Prior malignancy is not an exclusion
• Participants with gastrointestinal tract disease (or uncontrolled vomiting or diarrhea) that could interfere with the absorption of eltanexor (or ASTX727 in Part G).
• Serious psychiatric or medical conditions that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give consent.
• 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):
• Time since the last prior therapy for treatment of RRMM:
• Radiation, chemotherapy, immunotherapy or any other anticancer therapy, including investigational anticancer therapy ≤ 2 weeks prior to C1D1
• Palliative steroids for disease related symptoms are allowed up to 3 days prior to C1D1.
• Participants must have recovered or stabilized (≤ Grade 1 or to their baseline) from toxicities related to their previous treatment except for alopecia
• 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.
• Grade > 2 peripheral neuropathy or Grade 2 peripheral neuropathy with pain within 2 weeks prior to C1D1.

Where it is running

• 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
• University of New Mexico — Albuquerque, New Mexico, United States
• Weill Cornell Medical College — New York, New York, United States
• (USO) Oncology Hematology Care — Cincinnati, Ohio, United States
• Ohio State University, The James Cancer Hospital and Solove Research Institute — Columbus, Ohio, United States
• University of Pennsylvania Abramson Cancer Center Clinical Research Unit — Philadelphia, Pennsylvania, United States
• Baptist Cancer Center — Memphis, Tennessee, United States
• Vanderbilt University Medical Center — Nashville, Tennessee, United States
• (USO) Texas Oncology Austin - Midtown — Austin, Texas, United States
• (USO) Texas Oncology (Dallas) — Dallas, Texas, United States
• MD Anderson Cancer Center — Houston, Texas, United States
• (USO) Texas Oncology (Tyler) — Tyler, Texas, United States
• Huntsman Cancer Institute — Salt Lake City, Utah, United States
• University of Virginia — Charlottesville, Virginia, United States
• (USO) Virginia Cancer Specialists — Fairfax, Virginia, United States
• University of Washington — Seattle, Washington, United States

Full record on ClinicalTrials.gov

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