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RecruitingInterventionalPhase 1

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

NCT ID: NCT05651932Sponsor: K36 Therapeutics, Inc.Last updated: 2026-06-08

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.

Arms & interventions

  • DrugCohort A1 & A2: KTX-1001

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

  • DrugCohort 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

  • DrugCohort 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

  • DrugCohort 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

Outcome measures

Primary

  • 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

    Time frame: Cycle 1 (28 days)

Secondary

  • Disease Specific Response to KTX-1001± Combination Therapy

    Time frame: Duration of Study

  • Pharmacokinetics & Pharmacodynamics KTX-1001± Combination Therapy

    Time frame: Duration of Study

  • Safety profile of KTX-1001± Combination Therapy

    Time frame: Duration of Study

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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.

Study locations (13)

UCSF Medical Center - Hematology and Blood and Marrow Transplant Clinic

San Francisco, California, 94143

Recruiting
Alfred Chung, MD · Principal Investigator

Mayo Clinic Hospital - Florida

Jacksonville, Florida, 32224

Recruiting
Ahsan Rasheed · Contact
Vivek Roy, MD · Principal Investigator

The Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322

Recruiting
Sagar Lonial, MD, FACP · Principal Investigator

Massachusetts General Hospital

Boston, Massachusetts, 02114

Recruiting
Andrew Yee, MD · Contact
Andrew Yee, MD · Principal Investigator

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting
Yuxin Liu, MD · Contact
Yuxin Liu, MD · Principal Investigator

Mayo Clinic - Transplant Center - Rochester

Rochester, Minnesota, 55905

Recruiting
Thomas Nelson · Contact
David Dingli, MD, PhD · Principal Investigator

Hackensack University Medical Center

Hackensack, New Jersey, 07601

Recruiting
Palka Anand · Contact
David S Siegel, MD, PhD · Principal Investigator

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065

Recruiting
Mary Silverberg · Contact
Sharon Kim · Contact
Saad Usmani, MD, FACP · Principal Investigator

Atrium Health, Levine Cancer Institute

Charlotte, North Carolina, 28204

Recruiting
Missy Leahy · Contact
Cindy Varga, MD · Principal Investigator

Duke University Hospital

Durham, North Carolina, 27705

Recruiting
Cristina Gasparetto, MD · Principal Investigator

University of Pennsylvania

Philadelphia, Pennsylvania, 19104

Recruiting
Sara Whittington · Contact
Ed Stadtmauer, MD · Principal Investigator

Tennessee Oncology

Nashville, Tennessee, 37203

Recruiting
Austin Windsor · Contact
Jesus Berdeja, MD · Principal Investigator

University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center

Dallas, Texas, 75235

Recruiting
Aimaz Afrough, MD · Principal Investigator