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
K36 Therapeutics, Inc.
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).
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.
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Key Inclusion Criteria for Dose-Expansion: * ≥ 18 years of age * ECOG score ≤ 1 * Multiple myeloma (as per IMWG) * ≥ 3 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 antibody * Patients must be refractory to their last prior therapy * Cohorts A1/A2: Patients must have exhausted available therapeutic options that are expected to provide a meaningful clinical benefit, either through disease relapse, treatment refractory disease, intolerance, or refusal of the therapy * t(4;14) confirmed by standard of care FISH testing * Measurable disease, including at least 1 of th…
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
Locations (22)
- UCSF Medical Center - Hematology and Blood and Marrow Transplant ClinicSan Francisco, California
- Mayo Clinic Hospital - FloridaJacksonville, Florida
- The Winship Cancer Institute of Emory UniversityAtlanta, Georgia
- Massachusetts General HospitalBoston, Massachusetts
- Dana-Farber Cancer InstituteBoston, Massachusetts
- Mayo Clinic - Transplant Center - RochesterRochester, Minnesota