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).
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
125
KTX-1001: Orally for 28 days each cycle until progression. Dexamethasone: Orally once weekly
Drug: KTX-1001: Orally for 28 days each cycle until progression Drug: Dexamethasone: Orally once weekly Drug: Mezigdomide Dexamethasone: Orally once weekly
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
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)
Disease Specific Response to KTX-1001± Combination Therapy
Objective Response Rate (ORR) Duration of Response (DOR) Progression Free Survival (PFS) Minimal Residual Disease (MRD) Per IMWG Consensus Criteria for Response and Minimal Residual Disease Assessment in Multiple Myeloma
Time frame: Duration of Study
Pharmacokinetics & Pharmacodynamics KTX-1001± Combination Therapy
Maximum plasma concentration (Cmax) of KTX-1001 Time to achieve Cmax (tmax) for KTX-1001 Area under the plasma concentration-time curve (AUC) for KTX-1001
Time frame: Duration of Study
Safety profile of KTX-1001± Combination Therapy
Frequency and severity of TEAEs, treatment-related AEs, and clinically significant changes in laboratory test results
Time frame: Duration of Study
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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
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