Clinical trial NCT05651932: A Study of an MMSET Inhibitor in Patients with Relapsed and Refractory Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Myeloma
Myeloma Multiple
Keywords: NSD2
MMSET
WHSC1
T4;14
T(4;14)
translocation
myeloma
RRMM
Lead sponsor: K36 Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-12-15
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Key Inclusion Criteria for Dose-Expansion:

* ≥ 18 years of age
* ECOG score ≤ 1
* Multiple myeloma (as per IMWG)

  * ≥ 3 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 antibody
  * Patients must be refractory to their last prior therapy
  * Cohorts A1/A2: 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
* 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:

  * 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
* MM with extramedullary disease
* 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
* 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 outcomes:
measure: Dose Escalation: Determination of Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose (MTD)
timeFrame: Cycle 1 (28 days)
Secondary outcomes:
measure: Disease Specific Response to KTX-1001± Combination Therapy
timeFrame: Duration of Study
measure: Pharmacokinetics & Pharmacodynamics KTX-1001± Combination Therapy
timeFrame: Cycle 1 (28 days)
measure: Safety profile of KTX-1001± Combination Therapy
timeFrame: Duration of Study
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Medical Center - Hematology and Blood and Marrow Transplant Clinic
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Hospital - Florida
state: Florida
city: Atlanta
country: United States
facility: The Winship Cancer Institute of Emory University
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Transplant Center - Rochester
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Atrium Health, Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center
state: Texas
city: Toronto
country: Canada
facility: University Health Network (UHN) - Princess Margaret Cancer Centre (Princess Margaret Hospital)
state: Ontario
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse - Oncopole
city: Villeneuve-d'Ascq
country: France
facility: Universitaire de Lille
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital ClÃ-nic de Barcelona
city: Salamanca
country: Spain
facility: Instituto de Investigacion Biomedica de Salamanca (IBSAL)
Study officials:
References: