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

Phase 1

Recruiting

• Conditions: Myeloma; Multiple Myeloma; Myeloma Multiple
• Interventions: Drug: Cohort A1 & A2; Drug: Cohort B1 & B2; Drug: Cohort C1 & C2; Drug: Cohort D

• Registration Number: NCT05651932
• Lead Sponsor: K36 Therapeutics, Inc.

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).

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.

Study Timeline

• Study First Submitted: 2022-12-01
• Study First Submitted QC: 2022-12-13
• Study First Posted: 2022-12-15
• Study Start: 2023-02-22
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-10
• Last Update Posted: 2025-07-15
• Primary Completion: 2025-12-31
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 125

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort A (Single agent): KTX-1001 + dexamethasone	Cohort A1 & A2	Cohort A1 (single agent): KTX-1001 at RP2D1 + dex Cohort A2 (single agent): KTX-1001 at RP2D2 + dex
Cohort B (Mezigdomide): KTX-1001 + Mezigdomide + dex	Cohort B1 & B2	Cohort B1 (Mezigdomide): KTX-1001 at RP2D1 + Mezigdomide + dex Cohort B2 (Mezigdomide):: KTX-1001 at RP2D2 + Mezigdomide + dex
Cohort C (carfilzomib): KTX-1001 + carfilzomib + dex	Cohort C1 & C2	Cohort C1 (carfilzomib): KTX-1001 at RP2D1 + carfilzomib + dex Cohort C2 (carfilzomib): KTX-1001 at RP2D2 + carfilzomib + dex
Cohort D (pomalidomide): KTX-1001 + pomalidomide + dex	Cohort D	Cohort D (pomalidomide): KTX-1001 at RP2D1 or RP2D2 + pomalidomide + dex

Primary Outcome Measures

Name	Time	Method
Dose Escalation: Determination of Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose (MTD)	Cycle 1 (28 days)	Incidence of dose-limiting toxicity (DLTs), treatment-emergent adverse events (TEAEs), treatment-related AEs, and clinically significant changes in laboratory test results

Secondary Outcome Measures

Name	Time	Method
Disease Specific Response to KTX-1001± Combination Therapy	Duration of Study	Objective Response Rate (ORR) Duration of Response (DOR) Progression Free Survival (PFS) Minimal Residual Disease (MRD); Per IMWG Consensus Criteria for Response and Minimal Residual Disease Assessment in Multiple Myeloma
Pharmacokinetics & Pharmacodynamics KTX-1001± Combination Therapy	Duration of Study	Maximum plasma concentration (Cmax) of KTX-1001 Time to achieve Cmax (tmax) for KTX-1001 Area under the plasma concentration-time curve (AUC) for KTX-1001
Safety profile of KTX-1001± Combination Therapy	Duration of Study	Frequency and severity of TEAEs, treatment-related AEs, and clinically significant changes in laboratory test results

Trial Locations

Locations (21)

UCSF Medical Center - Hematology and Blood and Marrow Transplant Clinic; 🇺🇸 San Francisco, California, United States

Mayo Clinic Hospital - Florida; 🇺🇸 Jacksonville, Florida, United States

The Winship Cancer Institute of Emory University; 🇺🇸 Atlanta, Georgia, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Mayo Clinic - Transplant Center - Rochester; 🇺🇸 Rochester, Minnesota, United States

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States

Atrium Health, Levine Cancer Institute; 🇺🇸 Charlotte, North Carolina, United States

Duke University Hospital; 🇺🇸 Durham, North Carolina, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

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