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

Sponsor

K36 Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05651932

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma Myeloma Myeloma Multiple	Drug: KTX-1001	Phase 1

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 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: KTX-1001 KTX-1001 will be administered orally, daily for 28 days.	Drug: KTX-1001 KTX-1001 will be administered orally, daily for 28 days.

Arm

Intervention/Treatment

Experimental: KTX-1001

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

Drug: KTX-1001

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

Outcome Measures

Primary Outcome Measures

Incidence of dose-limiting toxicity (DLTs) [Cycle 1 (28 days)]
Treatment-emergent adverse events (AEs), treatment-related AEs, and clinically significant changes in laboratory test results will be evaluated

Secondary Outcome Measures

Maximum plasma concentration (Cmax) of KTX-1001 [Cycle 1 (28 days)]
Time to achieve Cmax (tmax) for KTX-1001 [Cycle 1 (28 days)]
Area under the plasma concentration-time curve (AUC) for KTX-1001 [Cycle 1 (28 days)]
Objective response rate (ORR) for KTX-1001 [Cycle 1 (28 days)]
Per IMWG Consensus Criteria for Response and Minimal Residual Disease Assessment in Multiple Myeloma
Duration of response (DOR) for KTX-1001 [Cycle 1 (28 days)]
Progression-free survival (PFS) for KTX-1001 [Cycle 1 (28 days)]
Overall survival (OS) for KTX-1001 [Cycle 1 (28 days)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259
2	Mayo Clinic	Jacksonville	Florida	United States	32224
3	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
4	Mayo Clinic	Rochester	Minnesota	United States	55905
5	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
6	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee	United States	37203