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

October 23, 2023 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 translocation t(4;14) or a GOF mutation in MMSET (eg, E1099K) will be enrolled. Patients will receive KTX-1001 at the RP2D to further define safety and tolerability and provide preliminary efficacy information.

Study Type

Interventional

Enrollment (Estimated)

60

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)
        • Contact:
        • Contact:
        • Principal Investigator:
          • Suzanne Trudel, MSc, MD
  • France
      • Nantes, France
        • Recruiting
        • Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
        • Principal Investigator:
          • Cyrille Touzeau, MD
        • Contact:
        • Contact:
      • Toulouse, France
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Hospital ClÃ-nic de Barcelona
        • Contact:
        • Contact:
        • Principal Investigator:
          • Laura Rosinol, MD, PhD
      • Salamanca, Spain
        • Recruiting
        • Instituto de Investigacion Biomedica de Salamanca (IBSAL)
        • Contact:
          • Maria-Victoria Mateos Manteca, MD, PhD
          • Phone Number: 56933 +34 92329-1100
          • Email: mvmateos@usal.es
        • Contact:
        • Principal Investigator:
          • Maria-Victoria Mateos Manteca, MD, PhD
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Recruiting
        • Clinica Universidad de Navarra
        • Contact:
        • Contact:
          • Joana Sofia Reis de Carvlaho
          • Phone Number: +34 94825-5400
          • Email: jreis@unav.es
        • Principal Investigator:
          • Paula Rodriguez, MD, PhD
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85259
        • Recruiting
        • Mayo Clinic Hospital - Phoenix
        • Contact:
        • Contact:
        • Principal Investigator:
          • Peter Bergsagel, MD
    • California
      • San Francisco, California, United States, 94143
        • Recruiting
        • UCSF Medical Center - Hematology and Blood and Marrow Transplant Clinic
        • Principal Investigator:
          • Alfred Chung, MD
        • Contact:
        • Contact:
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic Hospital - Florida
        • Contact:
        • Contact:
        • Principal Investigator:
          • Vivek Roy, MD
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • The Winship Cancer Institute of Emory University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Sagar Lonial, MD, FACP
    • Kansas
      • Westwood, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Cancer Center - Fairway
        • Principal Investigator:
          • Al-Ola Abdallah, MD
        • Contact:
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
        • Principal Investigator:
          • Andrew Yee, MD
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic - Transplant Center - Rochester
        • Contact:
        • Contact:
        • Principal Investigator:
          • David Dingli, MD, PhD
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Hackensack University Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • David S Siegel, MD, PhD
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan-Kettering Cancer Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Saad Usmani, MD, MBA, FACP
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Recruiting
        • Duke University Hospital
        • Principal Investigator:
          • Cristina Gasparetto, MD
        • Contact:
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Tennessee Oncology
        • Contact:
        • Principal Investigator:
          • Jesus Berdeja, MD
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75235

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:

  • ≥ 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.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: KTX-1001
KTX-1001 will be administered orally, daily for 28 days.
Drug: KTX-1001
KTX-1001 will be administered orally, daily for 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of dose-limiting toxicity (DLTs)
Time Frame: Cycle 1 (28 days)
Treatment-emergent adverse events (AEs), treatment-related AEs, and clinically significant changes in laboratory test results will be evaluated
Cycle 1 (28 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum plasma concentration (Cmax) of KTX-1001
Time Frame: Cycle 1 (28 days)
Cycle 1 (28 days)
Time to achieve Cmax (tmax) for KTX-1001
Time Frame: Cycle 1 (28 days)
Cycle 1 (28 days)
Area under the plasma concentration-time curve (AUC) for KTX-1001
Time Frame: Cycle 1 (28 days)
Cycle 1 (28 days)
Objective response rate (ORR) for KTX-1001
Time Frame: Cycle 1 (28 days)
Per IMWG Consensus Criteria for Response and Minimal Residual Disease Assessment in Multiple Myeloma
Cycle 1 (28 days)
Duration of response (DOR) for KTX-1001
Time Frame: Cycle 1 (28 days)
Cycle 1 (28 days)
Progression-free survival (PFS) for KTX-1001
Time Frame: Cycle 1 (28 days)
Cycle 1 (28 days)
Overall survival (OS) for KTX-1001
Time Frame: Cycle 1 (28 days)
Cycle 1 (28 days)

Collaborators and Investigators

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

Sponsor

K36 Therapeutics, Inc.

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 1, 2024

Study Completion (Estimated)

October 1, 2025

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)

October 24, 2023

Last Update Submitted That Met QC Criteria

October 23, 2023

Last Verified

October 1, 2023

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)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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