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

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.