A Study of an MMSET Inhibitor in Patients With Relapsed and Refractory Multiple Myeloma
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
K36 Therapeutics, Inc.
125 participants
Feb 22, 2023
INTERVENTIONAL
Conditions
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
Inclusion Criteria14
- ≥ 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)
Exclusion Criteria17
- 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
- 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.
Interventions
KTX-1001: Orally for 28 days each cycle until progression. Dexamethasone: Orally once weekly
Drug: KTX-1001: Orally for 28 days each cycle until progression Drug: Dexamethasone: Orally once weekly Drug: Mezigdomide Dexamethasone: Orally once weekly
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
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
Locations(22)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05651932