A Study of an MMSET Inhibitor in Patients with Relapsed and Refractory Multiple Myeloma
Purpose
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).
Conditions
- Multiple Myeloma
- Myeloma
- Myeloma Multiple
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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 the following criteria: - Serum M protein ≥ 0.50 g/dL (by SPEP) - Serum IgA ≥ 0.50 g/dL (IgA myeloma patients) - Urine M protein ≥ 200 mg/24 h (by UPEP) - sFLC involved light chain ≥ 10 mg/dL (100 mg/L) (patients with abnormal sFLC ratio) - Bone marrow plasma cells ≥ 30% (if only criterion for measurability) - Agreement to enroll into the REMS program (Cohort D- pomalidomide cohort only)
Exclusion Criteria
for Dose-Expansion: - Treatment with the following therapies in the specified time period prior to first dose: - Carfilzomib in the immediate last prior line of therapy for patients enrolled in Cohorts C1 and C2 - Pomalidomide in the immediate last prior line of therapy for patients enrolled in cohort D - Radiation, chemotherapy, immunotherapy, or any other anticancer therapy ≤ 2 weeks - Cellular therapies ≤ 8 weeks - Autologous transplant < 100 days - Allogenic transplant ≤ 6 months, or > 6 months with active GVHD - Major surgery ≤ 4 weeks - Current plasma cell leukemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, solitary bone lesion or bone lesions as the only evidence for plasma cell dyscrasia, myelodysplastic syndrome or a myeloproliferative neoplasm or light chain amyloidosis - MM with extramedullary disease - Active CNS disease - Inadequate bone marrow function - Inadequate renal, hepatic, pulmonary, and cardiac function - Active, ongoing, or uncontrolled systemic viral, bacterial, or fungal infection. Permitted prophylactic medications, antimicrobials or antiretroviral therapies defined in protocol. - Use of acid reducing agents and strong inhibitors or inducers of CYP3A4 within 14 days or 5 half-lives prior to first dose - Strong CYP1A2 inhibitors for patients receiving pomalidomide (Cohort D) - Active malignancy not related to myeloma requiring therapy within < 2 years prior to enrollment, or not in complete remission, with exceptions defined in protocol.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental Cohort A (Single agent): KTX-1001 + dexamethasone (DEX) |
Cohort A1 (single agent): KTX-1001 at RP2D1 + DEX Cohort A2 (single agent): KTX-1001 at RP2D2 + DEX |
|
Experimental Cohort C (carfilzomib): KTX-1001 + DEX + carfilzomib |
Cohort C1 (carfilzomib): KTX-1001 at RP2D1 + DEX + carfilzomib Cohort C2 (carfilzomib): KTX-1001 at RP2D2 + DEX + carfilzomib |
|
Experimental Cohort D (pomalidomide): KTX-1001 + DEX + pomalidomide |
Cohort D (pomalidomide): KTX-1001 at RP2D1/2 + DEX + pomalidomide |
|
Recruiting Locations
More Details
- Status
- Recruiting
- Sponsor
- K36 Therapeutics, Inc.
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 SOC therapy (dexamethasone, carfilzomib or pomalidomide) to further define safety and tolerability and provide preliminary efficacy information.