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.