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

ArmDescriptionAssigned 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
  • Drug: Cohort A1 & A2
    KTX-1001 will be administered orally for 28 days each cycle until progression. Dexamethasone: Orally once weekly
    Other names:
    • KTX-1001
    • Dexamethasone
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
  • Drug: Cohort C1 & C2
    KTX-1001: Orally for 28 days each cycle until progression Carfilzomib: IV, once weekly for 3 weeks in each 28-day cycle Dexamethasone: Orally once weekly
    Other names:
    • Carfilzomib
    • Dexamethasone
Experimental
Cohort D (pomalidomide): KTX-1001 + DEX + pomalidomide
Cohort D (pomalidomide): KTX-1001 at RP2D1/2 + DEX + pomalidomide
  • Drug: Cohort D
    KTX-1001: Orally daily for 28 days each cycle until progression Pomalidomide: Orally, for 21 days in each 28-day cycle Dexamethasone: Orally once a week
    Other names:
    • Pomalidomide
    • Dexamethasone

Recruiting Locations

More Details

Status
Recruiting
Sponsor
K36 Therapeutics, Inc.

Study Contact

Soo Bang
1-347-342-7199
sbang@k36tx.com

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.