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

What this study is about

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).

Who can join (things the study team will check)

✅ You may be able to join if…

• ≥ 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)

🚫 You may not be able to join if…

• 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.

Where this trial is running

• UCSF Medical Center - Hematology and Blood and Marrow Transplant Clinic, San Francisco, California, United States
• Mayo Clinic Hospital - Florida, Jacksonville, Florida, United States
• The Winship Cancer Institute of Emory University, Atlanta, Georgia, United States
• Massachusetts General Hospital, Boston, Massachusetts, United States
• Dana-Farber Cancer Institute, Boston, Massachusetts, United States
• Mayo Clinic - Transplant Center - Rochester, Rochester, Minnesota, United States
• Hackensack University Medical Center, Hackensack, New Jersey, United States
• Memorial Sloan-Kettering Cancer Center, New York, New York, United States
• Atrium Health, Levine Cancer Institute, Charlotte, North Carolina, United States
• Duke University Hospital, Durham, North Carolina, United States
• University of Pennsylvania, Philadelphia, Pennsylvania, United States
• Tennessee Oncology, Nashville, Tennessee, United States

+ 10 more sites.

Who to contact

Soo Bang, MHSA · 1-347-342-7199 · sbang@k36tx.com

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT05651932.