A Study of an MMSET Inhibitor in Patients With Relapsed and Refractory Multiple Myeloma MMSET INHIBITOR

What's the purpose of this trial?

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).

This trial is currently open and accepting patients.

What will happen during the trial?

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.

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Key Inclusion Criteria:

  • ≥ 18 years of age
  • ECOG score ≤ 2
  • Relapsed or refractory multiple myeloma (as per IMWG)
    • ≥ 3 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 antibody
    • 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, or GOF mutation in MMSET confirmed by local sequencing test (Part B dose expansion cohorts only)
  • 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)
    • ≥ 1 extramedullary lesion ≥ 1 cm in size and able to be followed by imaging assessments (Part A dose escalation cohorts only)
    • Bone marrow plasma cells ≥ 10% (Part A dose escalation cohorts only)

Key Exclusion Criteria:

  • Treatment with the following therapies in the specified time period prior to first dose:
    • 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
  • History of or 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
  • 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
  • Active malignancy not related to myeloma requiring therapy within < 3 years prior to enrollment, or not in complete remission, with exceptions defined in protocol.

Additional Trial Information

Phase 1

Enrollment: 125 patients (estimated)

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Published Results

First Results from the Dose Escalation Part of the Phase 1 Study of KTX1001, an Oral, First-in-Class, Potent Inhibitor of MMSET/NSD2 for Relapsed/Refractory Multiple Myeloma (RRMM)

November 05, 2024

As of June 14, 2024, 17 patients (pts) have been treated with KTX-1001 in Part A across 6 dose levels (SRC reviewed). Dose Level 7 has been reached with no dose limiting toxicities (DLTs). Ten of these patients are t(4;14) positive. Patients have received a median of 5 prior lines of therapy (range: 3-17), including 7 pts with prior BCMA CAR-T, 6 pts with prior BCMA bispecific and/or ADC, 5 pts with prior non-BCMA bispecific, and 12 pts with prior transplant. Patient demographics include a median age of 68 years (range: 50-83), 10 male/ 7 female, 13 white, 2 black or African American, 2 as other identified race, and 3 Hispanic or Latino pts. Six pts remain on treatment. KTX-1001 shows excellent tolerability to date, with treatment emergent AEs (TEAEs) (CTCAEv5.0) predominantly of grade 1 and 2 severity. Most frequently observed TEAEs suspected to be related to KTX-1001 include fatigue (35%), diarrhea (24%), and constipation (24%), for which no grade 3 or 4 events have been observed. Frequency and/or severity of TEAEs have not increased with escalating doses nor treatment duration, and no patients have discontinued due to an AE. Two heavily pre-treated patients [one known to be t(4;14)+] have demonstrated long-lasting stable disease and clinical benefit at 10 and 7 months respectively.

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Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

California

UCSF Helen Diller Comprehensive Cancer Center University of California San Francisco

San Francisco, CA

Open and Accepting

Florida

Mayo Clinic (Jacksonville)

Jacksonville, FL

Open and Accepting

Georgia

Winship Cancer Institute Emory University

Atlanta, GA

Open and Accepting

Massachusetts

Massachusetts General Hospital

Boston, MA

Open and Accepting

Minnesota

Mayo Clinic (Rochester)

Rochester, MN

Open and Accepting

New Jersey

John Theurer Cancer Center at Hackensack University Medical Center  Hackensack Meridian Health

Hackensack, NJ

Open and Accepting

New York

Memorial Sloan Kettering Cancer Center

New York, NY

Open and Accepting

North Carolina

Atrium Health's Levine Cancer Institute - Charlotte (Main) Atrium Health

Charlotte, NC

Open and Accepting

Duke Cancer Center Duke University Medical Center

Durham, NC

Open and Accepting

Tennessee

Sarah Cannon Research Institute at Tennessee Oncology TriStar Centennial Medical Center

Nashville, TN

Open and Accepting

Texas

The University of Texas Southwestern Medical Center Harold C. Simmons Comprehensive Cancer Center

Dallas, TX

Open and Accepting
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