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

NCT ID: NCT05651932

Last Updated: 2026-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

125 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-22

Study Completion Date

2028-06-30

Brief Summary

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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

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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.

Conditions

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Multiple Myeloma Myeloma Myeloma Multiple

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Cohort A1 & A2: KTX-1001

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

Cohort B1 & B2: KTX-1001+Mezigdomide

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

Cohort C1 & C2: KTX-1001 + Carfilzomib (KYPROLIS®)

Intervention Type DRUG

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

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

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

Group Type EXPERIMENTAL

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

Intervention Type DRUG

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

Interventions

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Cohort A1 & A2: KTX-1001

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

Intervention Type 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

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

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KTX-1001 Dexamethasone Mezigdomide Carfilzomib (KYPROLIS®) Dexamethasone Pomalidomide (Pomalyst, Imnovid) Dexamethasone

Eligibility Criteria

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Inclusion Criteria

* ≥ 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)

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

K36 Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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UCSF Medical Center - Hematology and Blood and Marrow Transplant Clinic

San Francisco, California, United States

Site Status RECRUITING

Mayo Clinic Hospital - Florida

Jacksonville, Florida, United States

Site Status RECRUITING

The Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Mayo Clinic - Transplant Center - Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status RECRUITING

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Atrium Health, Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status RECRUITING

Duke University Hospital

Durham, North Carolina, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Tennessee Oncology

Nashville, Tennessee, United States

Site Status RECRUITING

University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center

Dallas, Texas, United States

Site Status RECRUITING

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

Toronto, Ontario, Canada

Site Status RECRUITING

Universitaire de Lille

Villeneuve-d'Ascq, France, France

Site Status RECRUITING

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

Nantes, , France

Site Status RECRUITING

Centre Hospitalier Universitaire de Poitiers (CHU de Poitiers)

Poitiers, , France

Site Status RECRUITING

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, , France

Site Status RECRUITING

Clínica Universidad de Navarra

Pamplona, Navarre, Spain

Site Status RECRUITING

Hospital ClÃ-nic de Barcelona

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Instituto de Investigacion Biomedica de Salamanca (IBSAL)

Salamanca, , Spain

Site Status RECRUITING

Countries

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United States Canada France Spain

Central Contacts

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Soo Bang, MHSA

Role: CONTACT

1-347-342-7199

Miriam Barnett, Ph.D.

Role: CONTACT

1-716-523-2141

Facility Contacts

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Phu Lam

Role: primary

415-858-7994

Ahsan Rasheed

Role: primary

904-953-2000

Geraldine Onwuzor

Role: primary

404-778-5144

Alicia Marggraf

Role: primary

617-724-7319

Thomas Nelson

Role: primary

855-776-0015

Palka Anand

Role: primary

551-996-3040

Laura Guttentag

Role: primary

646-415-4804

Kelly Bumgarnert

Role: primary

Quinna Lawson

Role: primary

919-668-2556

Sara Whittington

Role: primary

Austin Windsor

Role: primary

629-278-3554

Yu (Joyce) Wang

Role: primary

214-645-9859

Saima Dean

Role: primary

416-946-4501 ext. 5241

Salomon Manier, MD

Role: primary

03 59 50 75 69

Laetitia Mallard

Role: primary

+33 2 40 08 32 14

Romane Giraud

Role: primary

+33 5 16 60 43 06

Alicia Perez

Role: primary

Raquel Antón Saiz

Role: primary

+34 948 255 400 ext. 2754

Julio Vidal

Role: primary

+34 93 227 5484

Joaquín Martínez López, MD

Role: primary

+34 91 779 2877

Carmen Arias

Role: primary

+34 92 321 0960

Related Links

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Other Identifiers

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EUCTR No: 2022-500801-41-00

Identifier Type: OTHER

Identifier Source: secondary_id

KTX-MMSET-001

Identifier Type: -

Identifier Source: org_study_id

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