Cohort A1 & A2: KTX-1001: KTX-1001: Orally for 28 days each cycle until progression. Dexamethasone: Orally once weekly
Cohort 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
Cohort 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
Cohort 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
Study 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).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy 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.
Primary outcome measure(s)
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 — 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
Trial sites (26)
Facility
City
Region
Status
UCSF Medical Center - Hematology and Blood and Marrow Transplant Clinic
San Francisco
California
Recruiting
Mayo Clinic Hospital - Florida
Jacksonville
Florida
Recruiting
University of Miami Don Soffer Clinical Research Center
Miami
Florida
Not Yet Recruiting
The Winship Cancer Institute of Emory University
Atlanta
Georgia
Recruiting
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
Dana-Farber Cancer Institute
Boston
Massachusetts
Recruiting
Mayo Clinic - Transplant Center - Rochester
Rochester
Minnesota
Recruiting
Hackensack University Medical Center
Hackensack
New Jersey
Recruiting
Memorial Sloan-Kettering Cancer Center
New York
New York
Recruiting
Atrium Health, Levine Cancer Institute
Charlotte
North Carolina
Recruiting
Duke University Hospital
Durham
North Carolina
Recruiting
Cleveland Clinic - Taussig Cancer Institute
Cleveland
Ohio
Not Yet Recruiting
University of Pennsylvania
Philadelphia
Pennsylvania
Recruiting
Medical University of South Carolina (MUSC) - Hollings Cancer Center
Charleston
South Carolina
Recruiting
Tennessee Oncology
Nashville
Tennessee
Recruiting
University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center
Dallas
Texas
Recruiting
Northwest Medical Specialties
Tacoma
Washington
Not Yet Recruiting
University Health Network (UHN) - Princess Margaret Cancer Centre (Princess Margaret Hospital)
Toronto
Ontario
Recruiting
Universitaire de Lille
Villeneuve-d'Ascq
France
Recruiting
Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu
Nantes
France
Recruiting
Centre Hospitalier Universitaire de Poitiers (CHU de Poitiers)
Poitiers
France
Recruiting
Institut Universitaire du Cancer de Toulouse - Oncopole
Toulouse
France
Recruiting
Clínica Universidad de Navarra
Pamplona
Navarre
Recruiting
Hospital ClÃ-nic de Barcelona
Barcelona
Spain
Recruiting
Hospital Universitario 12 de Octubre
Madrid
Spain
Recruiting
Instituto de Investigacion Biomedica de Salamanca (IBSAL)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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