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NCT05651932PHASE1Recruiting

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

K36 Therapeutics, Inc.

Start Date

2/22/2023

Completion Date

6/30/2028

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).

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.

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion Criteria for Dose-Expansion: * ≥ 18 years of age * ECOG score ≤ 1 * Multiple myeloma (as per IMWG) * Prior therapy for MM: Participants must have received at least 1 and up to 3 prior lines of therapy as defined by IMWG, and the following drug classes: PI, IMiD, and anti-CD38 antibody. For mezigdomide combination Cohorts B1 and B2, participants must have received at least 2 prior lines of therapy * Participants must have a confirmed diagnosis of progressive MM (per IMWG), t(4;14) confirmed by fluorescence in situ hybridization (FISH) testing performed in a centralized Clinical Laboratory Improvement Amendments (CLIA) accredited laboratory via fresh tumor biopsy. * 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: participants with previously treated stable CNS disease are eligible, except for Cohorts B1 and B2 for which known CNS myeloma involvement is completely excluded. * 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 7 days or 5 half-lives (whichever is longer) 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.

Interventions

DRUG

Cohort A1 & A2: KTX-1001

DRUG

Cohort B1 & B2: KTX-1001+Mezigdomide

DRUG

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

DRUG

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

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Conditions

Multiple MyelomaMyelomaMyeloma Multiple

Locations

UCSF Medical Center - Hematology and Blood and Marrow Transplant Clinic

San Francisco, California 94143

United States

Mayo Clinic Hospital - Florida

Jacksonville, Florida 32224

United States

The Winship Cancer Institute of Emory University

Atlanta, Georgia 30322

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

Mayo Clinic - Transplant Center - Rochester

Rochester, Minnesota 55905

United States

Hackensack University Medical Center

Hackensack, New Jersey 07601

United States

Memorial Sloan-Kettering Cancer Center

New York, New York 10065

United States

Atrium Health, Levine Cancer Institute

Charlotte, North Carolina 28204

United States

Duke University Hospital

Durham, North Carolina 27705

United States

University of Pennsylvania

Philadelphia, Pennsylvania 19104

United States

Tennessee Oncology

Nashville, Tennessee 37203

United States

University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center

Dallas, Texas 75235

United States

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

Toronto, Ontario M5G 2C4

Canada

Universitaire de Lille

Villeneuve-d'Ascq, France

France

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

Nantes,

France

Centre Hospitalier Universitaire de Poitiers (CHU de Poitiers)

Poitiers,

France

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse,

France

Clínica Universidad de Navarra

Pamplona, Navarre 31008

Spain

Hospital ClÃ-nic de Barcelona

Barcelona,

Spain

Hospital Universitario 12 de Octubre

Madrid,

Spain

Instituto de Investigacion Biomedica de Salamanca (IBSAL)

Salamanca,

Spain