Multiple MyelomaPhase 1NCT05651932
A Study of an MMSET Inhibitor in Patients With Relapsed and Refractory Multiple Myeloma
A Phase 1 study testing Cohort A1 & A2: KTX-1001, Cohort B1 & B2: KTX-1001+Mezigdomide and Cohort C1 & C2: KTX-1001 + Carfilzomib (KYPROLIS®) in people with Multiple Myeloma and Myeloma, run by K36 Therapeutics, Inc. at 29 sites in 4 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma, Myeloma, Myeloma Multiple
- What is being tested?
- Cohort A1 & A2: KTX-1001, Cohort B1 & B2: KTX-1001+Mezigdomide and Cohort C1 & C2: KTX-1001 + Carfilzomib (KYPROLIS®)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 165 participants
- Where
- 29 sitesin 4 countries
- Study dates
- 22 Feb 2023to 30 Jun 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 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:
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- 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)
Who cannot join
- 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
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- 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.
Trial locations and contacts
29 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
29 sites in 4 countries
United States19 sites, 19 recruiting
- Not yet recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Cancer Answer Line, 800-865-1125, canceranswerline@med.umich.edu
Matthew Pianko, MD
- Recruiting
The Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Geraldine Onwuzor, 404-778-5144, chika.geraldine.onwuzor@emory.edu
Sagar Lonial, MD, FACP
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Andrew Yee, MD, 617-724-4000
Andrew Yee, MD
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Yuxin Liu, MD, yuxin_liu@dfci.harvard.edu
Yuxin Liu, MD
- Recruiting
Medical University of South Carolina (MUSC) - Hollings Cancer Center
Charleston, South Carolina, 29425
Shata Salzer, 843-792-1463, salzers@musc.edu
Anthony Dominick, DO
- Recruiting
Atrium Health, Levine Cancer Institute
Charlotte, North Carolina, 28204
Missy Leahy, melissa.leahy@advocatehealth.org
Cindy Varga, MD
- Recruiting
Cleveland Clinic - Taussig Cancer Institute
Cleveland, Ohio, 44195
Cancer Answer Line, 216-444-7923, CancerAnswer@ccf.org
Louis Williams, MD
- Recruiting
University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center
Dallas, Texas, 75235
Aimaz Afrough, MD, 833-722-6237, aimaz.afrough@utsouthwestern.edu
Aimaz Afrough, MD
- Recruiting
Duke University Hospital
Durham, North Carolina, 27705
Jen Tichon, 919-660-7262, jennifer.tichon@duke.edu
Cristina Gasparetto, MD
- Recruiting
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Palka Anand, 551-996-3040, Palka.Anand@hmhn.org
David S Siegel, MD, PhD
- Recruiting
Oncology Consultants
Houston, Texas, 77030
Dr. Julio A. Peguero, MD, 713-600-0900, Jpeguero@oncologyconsultants.com
Julio A Peguero, MD
- Recruiting
Mayo Clinic Hospital - Florida
Jacksonville, Florida, 32224
Ahsan Rasheed, 904-953-2000, rasheed.ahsan@mayo.edu
Vivek Roy, MD
- Not yet recruiting
University of Miami Don Soffer Clinical Research Center
Miami, Florida, 33136
Michelle Armogan, 305-243-7479, mda182@miami.edu
Dickran Kazandjian, MD
- Recruiting
Tennessee Oncology
Nashville, Tennessee, 37203
Austin Windsor, 629-278-3554, awindsor@tnonc.com
Jesus Berdeja, MD
- Recruiting
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Mary Silverberg, silverb1@mskcc.org
Sharon Kim, kims13@mskcc.org
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Sara Whittington, sara.whittington@pennmedicine.upenn.edu
Ed Stadtmauer, MD
- Recruiting
Mayo Clinic - Transplant Center - Rochester
Rochester, Minnesota, 55905
Thomas Nelson, 855-776-0015, nelson.thomas2@mayo.edu
David Dingli, MD, PhD
- Recruiting
UCSF Medical Center - Hematology and Blood and Marrow Transplant Clinic
San Francisco, California, 94143
Phu Lam, 415-858-7994, phu.lam@ucsf.edu
Alfred Chung, MD
- Recruiting
Northwest Medical Specialties, PLLC
Tacoma, Washington, 98405
Sara Sandefur, 253-380-5299, ssandefur@p1trials.com
Jorge Chaves, MD
France4 sites, 4 recruiting
- Recruiting
Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu
Nantes
Cyrille Touzeau, MD, 33 (0) 2 40 08 32 71, cyrille.touzeau@chu-nantes.fr
Cyrille Touzeau, MD
- Recruiting
Centre Hospitalier Universitaire de Poitiers (CHU de Poitiers)
Poitiers
Romane Giraud, +33 5 16 60 43 06, Romane.giraud@chu-poitiers.fr
Xavier Leleu, MD
- Recruiting
Institut Universitaire du Cancer de Toulouse - Oncopole
Toulouse
Pierre Bories, MD
- Recruiting
Universitaire de Lille
Villeneuve-d'Ascq, France
Salomon Manier, MD, 03 59 50 75 69, Salomon.manier@chru-lille.fr
Salomon Manier, MD
Spain4 sites, 4 recruiting
- Recruiting
Hospital ClÃ-nic de Barcelona
Barcelona
Julio Vidal, +34 93 227 5484, contratoshemato@recerca.clinic.cat
Laura Rosinol, MD, PhD
- Recruiting
Hospital Universitario 12 de Octubre
Madrid
Joaquín Martínez López, MD, +34 91 779 2877, jmarti01@med.ucm.es
Lucía Sánchez Pérez, (+34) 91 779 28 09, luciasanchez12imas@gmail.com
- Recruiting
Clínica Universidad de Navarra
Pamplona, Navarre, 31008
Ana Valcarcel, avalcarcelg@unav.es
Paula Rodriguez, MD, PhD
- Recruiting
Instituto de Investigacion Biomedica de Salamanca (IBSAL)
Salamanca
Carmen Arias, +34 92 329 1100 ext. 56094, ensayosclinicos@ibsal.es
Maria-Victoria Mateos Manteca, MD, PhD
Canada2 sites, 2 recruiting
- Not yet recruiting
Cross Cancer Institute
Edmonton, Alberta, T6G IZ2
Sandhu Iwindeep, 780-432-8221, irwindee@ualberta.ca
Sandhu Irwindeep, MD
- Recruiting
University Health Network (UHN) - Princess Margaret Cancer Centre (Princess Margaret Hospital)
Toronto, Ontario, M5G 2C4
Saima Dean, saima.dean@uhnresearch.ca
Suzanne Trudel, MSc, MD
About this study
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
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).
Read the 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.
- Conditions
- Multiple Myeloma, Myeloma, Myeloma Multiple
- Being tested
- Cohort A1 & A2: KTX-1001, Cohort B1 & B2: KTX-1001+Mezigdomide, Cohort C1 & C2: KTX-1001 + Carfilzomib (KYPROLIS®), Cohort D: KTX-1001+ pomalidomide (Pomalyst, Imnovid)
- Keywords
- NSD2, MMSET, WHSC1, T4;14, T(4;14), translocation, myeloma, RRMM
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cohort A1 & A2: KTX-1001Drug
Also called KTX-1001, Dexamethasone
KTX-1001: Orally for 28 days each cycle until progression. Dexamethasone: Orally once weekly
Cohort B1 & B2: KTX-1001+MezigdomideDrug
Also called 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
Also called Carfilzomib (KYPROLIS®), Dexamethasone
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
Also called Pomalidomide (Pomalyst, Imnovid), Dexamethasone
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 group | Role | What they receive |
|---|---|---|
| Cohort A (Single agent): KTX-1001 + dexamethasone | Experimental | Cohort A1 (single agent): KTX-1001 at RP2D1 + dex Cohort A2 (single agent): KTX-1001 at RP2D2 + dex Receives: Drug: Cohort A1 & A2: KTX-1001 |
| Cohort B (Mezigdomide): KTX-1001 + Mezigdomide + dex | Experimental | Cohort B1 (Mezigdomide): KTX-1001 at RP2D1 + Mezigdomide + dex Cohort B2 (Mezigdomide):: KTX-1001 at RP2D2 + Mezigdomide + dex Receives: Drug: Cohort B1 & B2: KTX-1001+Mezigdomide |
| Cohort C (carfilzomib/KYPROLIS®): KTX-1001 + carfilzomib + dex | Experimental | Cohort C1 (carfilzomib/KYPROLIS®): KTX-1001 at RP2D1 + carfilzomib + dex Cohort C2 (carfilzomib/KYPROLIS®): KTX-1001 at RP2D2 + carfilzomib + dex Receives: Drug: Cohort C1 & C2: KTX-1001 + Carfilzomib (KYPROLIS®) |
| Cohort D (pomalidomide): KTX-1001 + pomalidomide + dex | Experimental | Cohort D (pomalidomide): KTX-1001 at RP2D2 + pomalidomide + dex Receives: Drug: Cohort D: KTX-1001+ pomalidomide (Pomalyst, Imnovid) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Incidence of dose-limiting toxicity (DLTs), treatment-emergent adverse events (TEAEs), treatment-related AEs, and clinically significant changes in laboratory test results
Measured: Cycle 1 (28 days)
Secondary outcomes (3)
Disease Specific Response to KTX-1001± Combination Therapy
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
Measured: Duration of Study
Pharmacokinetics & Pharmacodynamics KTX-1001± Combination Therapy
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
Measured: Duration of Study
Safety profile of KTX-1001± Combination Therapy
Frequency and severity of TEAEs, treatment-related AEs, and clinically significant changes in laboratory test results
Measured: Duration of Study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2022
- Study start22 Feb 2023
- Primary completion31 Dec 2027 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 165 participants (estimated)
Sponsor and investigators
- Lead sponsor
- K36 Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05651932
- Sponsor's protocol ID
- KTX-MMSET-001
- Other IDs
- EUCTR No: 2022-500801-41-00
- Status last verified
- Aug 2026
- First submitted
- 1 Dec 2022
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided