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

February 6, 2026 updated by: K36 Therapeutics, Inc.

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 investigational therapy Mezigdomide or SOC therapy (dexamethasone, carfilzomib or pomalidomide) to further define safety and tolerability and provide preliminary efficacy information.

Study Type

Interventional

Enrollment (Estimated)

125

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • Recruiting
        • University Health Network (UHN) - Princess Margaret Cancer Centre (Princess Margaret Hospital)
        • Principal Investigator:
          • Suzanne Trudel, MSc, MD
        • Contact:
  • France
      • Nantes, France
        • Recruiting
        • Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
        • Principal Investigator:
          • Cyrille Touzeau, MD
        • Contact:
      • Poitiers, France
        • Recruiting
        • Centre Hospitalier Universitaire de Poitiers (CHU de Poitiers)
        • Principal Investigator:
          • Xavier Leleu, MD
        • Contact:
      • Toulouse, France
        • Recruiting
        • Institut Universitaire du Cancer de Toulouse - Oncopole
        • Principal Investigator:
          • Pierre Bories, MD
    • France
      • Villeneuve-d'Ascq, France, France
        • Recruiting
        • Universitaire de Lille
        • Contact:
        • Principal Investigator:
          • Salomon Manier, MD
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Hospital ClÃ-nic de Barcelona
        • Principal Investigator:
          • Laura Rosinol, MD, PhD
        • Contact:
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario 12 de Octubre
        • Principal Investigator:
          • Joaquín Martínez López, MD
        • Contact:
        • Contact:
      • Salamanca, Spain
        • Recruiting
        • Instituto de Investigacion Biomedica de Salamanca (IBSAL)
        • Principal Investigator:
          • Maria-Victoria Mateos Manteca, MD, PhD
        • Contact:
    • Navarre
      • Pamplona, Navarre, Spain, 31008
        • Recruiting
        • Clinica Universidad de Navarra
        • Principal Investigator:
          • Paula Rodriguez, MD, PhD
        • Contact:
  • United States
    • California
      • San Francisco, California, United States, 94143
        • Recruiting
        • UCSF Medical Center - Hematology and Blood and Marrow Transplant Clinic
        • Principal Investigator:
          • Alfred Chung, MD
        • Contact:
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic Hospital - Florida
        • Principal Investigator:
          • Vivek Roy, MD
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • The Winship Cancer Institute of Emory University
        • Principal Investigator:
          • Sagar Lonial, MD, FACP
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Andrew Yee, MD
        • Contact:
          • Andrew Yee, MD
          • Phone Number: 617-724-4000
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Principal Investigator:
          • Yuxin Liu, MD
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic - Transplant Center - Rochester
        • Contact:
        • Principal Investigator:
          • David Dingli, MD, PhD
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Hackensack University Medical Center
        • Contact:
        • Principal Investigator:
          • David S Siegel, MD, PhD
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan-Kettering Cancer Center
        • Contact:
        • Principal Investigator:
          • Saad Usmani, MD, FACP
        • Contact:
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
      • Durham, North Carolina, United States, 27705
        • Recruiting
        • Duke University Hospital
        • Principal Investigator:
          • Cristina Gasparetto, MD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Tennessee Oncology
        • Principal Investigator:
          • Jesus Berdeja, MD
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75235
        • Recruiting
        • University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center
        • Principal Investigator:
          • Aimaz Afrough, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key 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)

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
  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort A (Single agent): KTX-1001 + dexamethasone
Cohort A1 (single agent): KTX-1001 at RP2D1 + dex Cohort A2 (single agent): KTX-1001 at RP2D2 + dex
Drug: Cohort A1 & A2: KTX-1001
KTX-1001: Orally for 28 days each cycle until progression. Dexamethasone: Orally once weekly
Other Names:
  • Dexamethasone
  • KTX-1001
Experimental: Cohort B (Mezigdomide): KTX-1001 + Mezigdomide + dex
Cohort B1 (Mezigdomide): KTX-1001 at RP2D1 + Mezigdomide + dex Cohort B2 (Mezigdomide):: KTX-1001 at RP2D2 + Mezigdomide + dex
Drug: Cohort B1 & B2: KTX-1001+Mezigdomide
Drug: KTX-1001: Orally for 28 days each cycle until progression Drug: Dexamethasone: Orally once weekly Drug: Mezigdomide Dexamethasone: Orally once weekly
Other Names:
  • Mezigdomide
Experimental: Cohort D (pomalidomide): KTX-1001 + pomalidomide + dex
Cohort D (pomalidomide): KTX-1001 at RP2D1 or RP2D2 + pomalidomide + dex
Drug: Cohort D: KTX-1001+ pomalidomide (Pomalyst, Imnovid)
Drug: KTX-1001: Orally for 28 days each cycle until progression Drug: Dexamethasone: Orally once a week Drug: Pomalidomide (Pomalyst, Imnovid): Orally, for 21 days in each 28-day cycle
Other Names:
  • Dexamethasone
  • Pomalidomide (Pomalyst, Imnovid)
Experimental: Cohort C (carfilzomib/KYPROLIS®): KTX-1001 + carfilzomib + dex
Cohort C1 (carfilzomib/KYPROLIS®): KTX-1001 at RP2D1 + carfilzomib + dex Cohort C2 (carfilzomib/KYPROLIS®): KTX-1001 at RP2D2 + carfilzomib + dex
Drug: Cohort C1 & C2: KTX-1001 + Carfilzomib (KYPROLIS®)
Drug: KTX-1001: Orally for 28 days each cycle until progression Drug: Dexamethasone: Orally once weekly Drug: Carfilzomib (KYPROLIS®): IV, once weekly for 3 weeks in each 28-day cycle
Other Names:
  • Dexamethasone
  • Carfilzomib (KYPROLIS®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Escalation: Determination of Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose (MTD) Dose Expansion: Provide preliminary efficacy data on the antitumor effects of KTX-1001 in combination with other anti-myeloma therapy
Time Frame: Cycle 1 (28 days)
Incidence of dose-limiting toxicity (DLTs), treatment-emergent adverse events (TEAEs), treatment-related AEs, and clinically significant changes in laboratory test results
Cycle 1 (28 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Specific Response to KTX-1001± Combination Therapy
Time Frame: Duration of Study

Objective Response Rate (ORR) Duration of Response (DOR) Progression Free Survival (PFS) Minimal Residual Disease (MRD)

Per IMWG Consensus Criteria for Response and Minimal Residual Disease Assessment in Multiple Myeloma
Duration of Study
Safety profile of KTX-1001± Combination Therapy
Time Frame: Duration of Study
Frequency and severity of TEAEs, treatment-related AEs, and clinically significant changes in laboratory test results
Duration of Study
Pharmacokinetics & Pharmacodynamics KTX-1001± Combination Therapy
Time Frame: Duration of Study
Maximum plasma concentration (Cmax) of KTX-1001 Time to achieve Cmax (tmax) for KTX-1001 Area under the plasma concentration-time curve (AUC) for KTX-1001
Duration of Study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

K36 Therapeutics, Inc.

Collaborators

Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 22, 2023

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

June 30, 2028

Study Registration Dates

First Submitted

December 1, 2022

First Submitted That Met QC Criteria

December 13, 2022

First Posted (Actual)

December 15, 2022

Study Record Updates

Last Update Posted (Actual)

February 10, 2026

Last Update Submitted That Met QC Criteria

February 6, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KTX-MMSET-001
  • EUCTR No: 2022-500801-41-00 (Other Identifier: European Medicines Agency)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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