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 D; Drug: Cohort A1 & A2; Drug: Cohort C1 & C2

• 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 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: 2024-12
• Last Update Submitted: 2024-12-11
• Last Update Posted: 2024-12-16
• 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 D (pomalidomide): KTX-1001 + DEX + pomalidomide	Cohort D	Cohort D (pomalidomide): KTX-1001 at RP2D1/2 + DEX + pomalidomide
Cohort A (Single agent): KTX-1001 + dexamethasone (DEX)	Cohort A1 & A2	Cohort A1 (single agent): KTX-1001 at RP2D1 + DEX Cohort A2 (single agent): KTX-1001 at RP2D2 + DEX
Cohort C (carfilzomib): KTX-1001 + DEX + carfilzomib	Cohort C1 & C2	Cohort C1 (carfilzomib): KTX-1001 at RP2D1 + DEX + carfilzomib Cohort C2 (carfilzomib): KTX-1001 at RP2D2 + DEX + carfilzomib

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	Cycle 1 (28 days)	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 (19)

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

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

Universitaire de Lille; 🇫🇷 Villeneuve-d'Ascq, France

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

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

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center; 🇺🇸 Dallas, Texas, United States

University Health Network (UHN) - Princess Margaret Cancer Centre (Princess Margaret Hospital); 🇨🇦 Toronto, Ontario, Canada

Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu; 🇫🇷 Nantes, France

Clínica Universidad de Navarra; 🇪🇸 Pamplona, Navarra, Spain

Institut Universitaire du Cancer de Toulouse - Oncopole; 🇫🇷 Toulouse, France

Hospital ClÃ-nic de Barcelona; 🇪🇸 Barcelona, Spain

Instituto de Investigacion Biomedica de Salamanca (IBSAL); 🇪🇸 Salamanca, Spain