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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
First received
Last updated
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
Health authority
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.

Study Design


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)
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