NCT05651932

Brief Summary

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).

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
125

participants targeted

Target at P75+ for phase_1 multiple-myeloma

Timeline
26mo left

Started Feb 2023

Typical duration for phase_1 multiple-myeloma

Geographic Reach
4 countries

22 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress60%
Feb 2023Jun 2028

First Submitted

Initial submission to the registry

December 1, 2022

Completed
14 days until next milestone

First Posted

Study publicly available on registry

December 15, 2022

Completed
2 months until next milestone

Study Start

First participant enrolled

February 22, 2023

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2027

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2028

Last Updated

February 10, 2026

Status Verified

January 1, 2026

Enrollment Period

4.9 years

First QC Date

December 1, 2022

Last Update Submit

February 6, 2026

Conditions

Keywords

NSD2MMSETWHSC1T4;14T(4;14)translocationmyelomaRRMM

Outcome Measures

Primary Outcomes (1)

  • 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

    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 Outcomes (3)

  • Disease Specific Response to KTX-1001± Combination Therapy

    Duration of Study

  • Pharmacokinetics & Pharmacodynamics KTX-1001± Combination Therapy

    Duration of Study

  • Safety profile of KTX-1001± Combination Therapy

    Duration of Study

Study Arms (4)

Cohort A (Single agent): KTX-1001 + dexamethasone

EXPERIMENTAL

Cohort A1 (single agent): KTX-1001 at RP2D1 + dex Cohort A2 (single agent): KTX-1001 at RP2D2 + dex

Drug: Cohort A1 & A2: KTX-1001

Cohort B (Mezigdomide): KTX-1001 + Mezigdomide + dex

EXPERIMENTAL

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

Cohort C (carfilzomib/KYPROLIS®): KTX-1001 + carfilzomib + dex

EXPERIMENTAL

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®)

Cohort D (pomalidomide): KTX-1001 + pomalidomide + dex

EXPERIMENTAL

Cohort D (pomalidomide): KTX-1001 at RP2D1 or RP2D2 + pomalidomide + dex

Drug: Cohort D: KTX-1001+ pomalidomide (Pomalyst, Imnovid)

Interventions

KTX-1001: Orally for 28 days each cycle until progression. Dexamethasone: Orally once weekly

Also known as: KTX-1001, Dexamethasone
Cohort A (Single agent): KTX-1001 + dexamethasone

Drug: KTX-1001: Orally for 28 days each cycle until progression Drug: Dexamethasone: Orally once weekly Drug: Mezigdomide Dexamethasone: Orally once weekly

Also known as: Mezigdomide
Cohort B (Mezigdomide): KTX-1001 + Mezigdomide + dex

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

Also known as: Carfilzomib (KYPROLIS®), Dexamethasone
Cohort C (carfilzomib/KYPROLIS®): KTX-1001 + carfilzomib + dex

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

Also known as: Pomalidomide (Pomalyst, Imnovid), Dexamethasone
Cohort D (pomalidomide): KTX-1001 + pomalidomide + dex

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥ 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)

You may not qualify if:

  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (22)

UCSF Medical Center - Hematology and Blood and Marrow Transplant Clinic

San Francisco, California, 94143, United States

RECRUITING

Mayo Clinic Hospital - Florida

Jacksonville, Florida, 32224, United States

RECRUITING

The Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Mayo Clinic - Transplant Center - Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Atrium Health, Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

RECRUITING

Duke University Hospital

Durham, North Carolina, 27705, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center

Dallas, Texas, 75235, United States

RECRUITING

University Health Network (UHN) - Princess Margaret Cancer Centre (Princess Margaret Hospital)

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

Universitaire de Lille

Villeneuve-d'Ascq, France, France

RECRUITING

Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu

Nantes, France

RECRUITING

Centre Hospitalier Universitaire de Poitiers (CHU de Poitiers)

Poitiers, France

RECRUITING

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, France

RECRUITING

Clínica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

Hospital ClÃ-nic de Barcelona

Barcelona, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Spain

RECRUITING

Instituto de Investigacion Biomedica de Salamanca (IBSAL)

Salamanca, Spain

RECRUITING

Related Links

MeSH Terms

Conditions

Multiple MyelomaNeoplasms, Plasma Cell

Interventions

Dexamethasonecarfilzomibpomalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

PregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, Fluorinated

Central Study Contacts

Soo Bang, MHSA

CONTACT

Miriam Barnett, Ph.D.

CONTACT

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 1, 2022

First Posted

December 15, 2022

Study Start

February 22, 2023

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

June 30, 2028

Last Updated

February 10, 2026

Record last verified: 2026-01

Locations