A Phase 1 Study of KTX-1001, an Oral, First-In-Class, Selective, and Potent MMSET Catalytic Inhibitor That Suppresses H3K36me2 in Patients With Relapsed and Refractory Multiple Myeloma
Summary
A Phase I study to evaluate the safety of a novel, orally available, selective, and potent small molecule inhibitor of the histone lysine methyl transferase MMSET (also known as NSD2/WHSC1) to prevent the dimethylation of H3K36 in adult patients with relapsed or refractory multiple myeloma (RRMM).
Detailed description
This is a Phase I, open-label, dose-escalation and expansion study in adult patients with RRMM. In the dose escalation phase (Part A), patients will be evaluated for DLTs during Cycle 1 (28 days). The KTX-1001 MTD, RP2D, and schedule will be determined. In the dose expansion phase (Part B), patients with t(4;14) will receive KTX-1001 at the RP2D alone and in combination with investigational therapy Mezigdomide or SOC therapy (dexamethasone, carfilzomib or pomalidomide) to further define safety and tolerability and provide preliminary efficacy information.
Arms & interventions
- DrugCohort A1 & A2: KTX-1001
KTX-1001: Orally for 28 days each cycle until progression. Dexamethasone: Orally once weekly
- DrugCohort B1 & B2: KTX-1001+Mezigdomide
Drug: KTX-1001: Orally for 28 days each cycle until progression Drug: Dexamethasone: Orally once weekly Drug: Mezigdomide Dexamethasone: Orally once weekly
- DrugCohort C1 & C2: KTX-1001 + Carfilzomib (KYPROLIS®)
Drug: KTX-1001: Orally for 28 days each cycle until progression Drug: Dexamethasone: Orally once weekly Drug: Carfilzomib (KYPROLIS®): IV, once weekly for 3 weeks in each 28-day cycle
- DrugCohort D: KTX-1001+ pomalidomide (Pomalyst, Imnovid)
Drug: KTX-1001: Orally for 28 days each cycle until progression Drug: Dexamethasone: Orally once a week Drug: Pomalidomide (Pomalyst, Imnovid): Orally, for 21 days in each 28-day cycle
Outcome measures
Primary
Dose Escalation: Determination of Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose (MTD) Dose Expansion: Provide preliminary efficacy data on the antitumor effects of KTX-1001 in combination with other anti-myeloma therapy
Incidence of dose-limiting toxicity (DLTs), treatment-emergent adverse events (TEAEs), treatment-related AEs, and clinically significant changes in laboratory test results
Time frame: Cycle 1 (28 days)
Secondary
Disease Specific Response to KTX-1001± Combination Therapy
Time frame: Duration of Study
Pharmacokinetics & Pharmacodynamics KTX-1001± Combination Therapy
Time frame: Duration of Study
Safety profile of KTX-1001± Combination Therapy
Time frame: Duration of Study
Eligibility criteria
Study locations (13)
UCSF Medical Center - Hematology and Blood and Marrow Transplant Clinic
San Francisco, California, 94143
Mayo Clinic Hospital - Florida
Jacksonville, Florida, 32224
The Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Mayo Clinic - Transplant Center - Rochester
Rochester, Minnesota, 55905
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Atrium Health, Levine Cancer Institute
Charlotte, North Carolina, 28204
Duke University Hospital
Durham, North Carolina, 27705
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Tennessee Oncology
Nashville, Tennessee, 37203
University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center
Dallas, Texas, 75235