UPCC 44424 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

Study on Investigational Medication for Relapsed and Refractory Multiple Myeloma

Enrolling By Invitation
18 years or above
All
Phase 1
165 participants needed
1 Location

Brief description of study

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).

Detailed description of study

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 of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Multiple Myeloma, Myeloma, Myeloma Multiple
  • Age: 18 years or above
  • Gender: All

Key Inclusion Criteria for Dose-Expansion:

  • ≥ 18 years of age
  • ECOG score ≤ 1
  • Multiple myeloma (as per IMWG)
    • Prior therapy for MM: Participants must have received at least 1 and up to 3 prior lines of therapy as defined by IMWG, and the following drug classes: PI, IMiD, and anti-CD38 antibody. For mezigdomide combination Cohorts B1 and B2, participants must have received at least 2 prior lines of therapy
    • Participants must have a confirmed diagnosis of progressive MM (per IMWG), t(4;14) confirmed by fluorescence in situ hybridization (FISH) testing performed in a centralized Clinical Laboratory Improvement Amendments (CLIA) accredited laboratory via fresh tumor biopsy.
  • 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)

Key Exclusion Criteria for Dose-Expansion:

  • Treatment with the following therapies in the specified time period prior to first dose
    • Patients in Cohorts B1 and B2 must not have received prior mezigdomide treatment
    • 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

  • Active CNS disease: participants with previously treated stable CNS disease are eligible, except for Cohorts B1 and B2 for which known CNS myeloma involvement is completely excluded.
  • 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 7 days or 5 half-lives (whichever is longer) 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.

This study investigates the effects of an investigational medication on patients with relapsed and refractory multiple myeloma (RRMM). The purpose of the study is to evaluate the safety and effects of a selective inhibitor that targets a specific enzyme involved in the disease process.

Participants will undergo a dose-escalation phase to determine the maximum tolerated dose, followed by a dose-expansion phase where the investigational medication will be given alone or with standard treatments. The study will assess safety, tolerability, and preliminary effectiveness of the treatment.

  • Who can participate: Adults 18 years or older with relapsed or refractory multiple myeloma can participate. They must have had at least three prior treatments, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. Participants need to have measurable disease and meet specific health criteria.
  • Study details: Participants will take the investigational medication either alone or with standard treatments. The study will evaluate the effects and safety of the treatment regimen. Participants will be monitored for side effects and treatment responses.
Updated on 08 Jun 2026. Study ID: 24-1574
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