Mass General - Division of Clinical Research

for Dose-Expansion: - ≥ 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)

for Dose-Expansion: - Treatment with the following therapies in the specified time period prior to first dose: - 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 - MM with extramedullary disease - 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.