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

Key Inclusion Criteria for Dose-Expansion:

• ≥ 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)

Key Exclusion Criteria for Dose-Expansion:

• 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.