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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05651932
• Other study ID #: KTX-MMSET-001
• Secondary ID: EUCTR No: 2022-5
• Status: Recruiting
• Phase: Phase 1
• Start date: February 22, 2023
• Est. completion date: October 2025

Study information

• Verified date: October 2023
• Source: K36 Therapeutics, Inc.
• Contact: Soo Bang
• Phone: 1-347-342-7199
• Email: sbang[@]k36tx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 translocation t(4;14) or a GOF mutation in MMSET (eg, E1099K) will be enrolled. Patients will receive KTX-1001 at the RP2D to further define safety and tolerability and provide preliminary efficacy information.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• = 18 years of age
• ECOG score = 2
• Relapsed or refractory multiple myeloma (as per IMWG)
• = 3 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 antibody
• 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, or GOF mutation in MMSET confirmed by local sequencing test (Part B dose expansion cohorts only)
• 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)
• = 1 extramedullary lesion = 1 cm in size and able to be followed by imaging assessments (Part A dose escalation cohorts only)
• Bone marrow plasma cells = 10% (Part A dose escalation cohorts only)

Key Exclusion Criteria:

• Treatment with the following therapies in the specified time period prior to first

dose:

• 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
• History of or 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
• Active malignancy not related to myeloma requiring therapy within < 3 years prior to enrollment, or not in complete remission, with exceptions defined in protocol.

Related Conditions & MeSH terms

• Multiple Myeloma
• Myeloma
• Myeloma Multiple
• Neoplasms, Plasma Cell

Intervention

Drug:
• KTX-1001
KTX-1001 will be administered orally, daily for 28 days.

Locations

Country	Name	City	State
Canada	University Health Network (UHN) - Princess Margaret Cancer Centre (Princess Margaret Hospital)	Toronto	Ontario
France	Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu	Nantes
France	Institut Universitaire du Cancer de Toulouse - Oncopole	Toulouse
Spain	Hospital ClÃ-nic de Barcelona	Barcelona
Spain	Clínica Universidad de Navarra	Pamplona	Navarra
Spain	Instituto de Investigacion Biomedica de Salamanca (IBSAL)	Salamanca
United States	The Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center	Dallas	Texas
United States	Duke University Hospital	Durham	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Mayo Clinic Hospital - Florida	Jacksonville	Florida
United States	Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mayo Clinic Hospital - Phoenix	Phoenix	Arizona
United States	Mayo Clinic - Transplant Center - Rochester	Rochester	Minnesota
United States	UCSF Medical Center - Hematology and Blood and Marrow Transplant Clinic	San Francisco	California
United States	University of Kansas Cancer Center - Fairway	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
K36 Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicity (DLTs)	Treatment-emergent adverse events (AEs), treatment-related AEs, and clinically significant changes in laboratory test results will be evaluated	Cycle 1 (28 days)
Secondary	Maximum plasma concentration (Cmax) of KTX-1001		Cycle 1 (28 days)
Secondary	Time to achieve Cmax (tmax) for KTX-1001		Cycle 1 (28 days)
Secondary	Area under the plasma concentration-time curve (AUC) for KTX-1001		Cycle 1 (28 days)
Secondary	Objective response rate (ORR) for KTX-1001	Per IMWG Consensus Criteria for Response and Minimal Residual Disease Assessment in Multiple Myeloma	Cycle 1 (28 days)
Secondary	Duration of response (DOR) for KTX-1001		Cycle 1 (28 days)
Secondary	Progression-free survival (PFS) for KTX-1001		Cycle 1 (28 days)
Secondary	Overall survival (OS) for KTX-1001		Cycle 1 (28 days)