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A Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma

Description

Brief Summary
The primary objective of this study for the Safety Run-in Cohorts is to evaluate the safety and tolerability of magrolimab in combination with other anticancer therapies and to determine the recommended Phase 2 dose (RP2D) of magrolimab in participants with relapsed/refractory multiple myeloma (MM) for the following combinations: magrolimab + daratumumab, magrolimab + pomalidomide + dexamethasone, and magrolimab + bortezomib + dexamethasone. The primary objective of this study for the Dose Expansion Cohorts is to evaluate the efficacy of magrolimab in combination with other anticancer therapies in participants with relapsed/refractory multiple myeloma as determined by objective response rate (ORR).


Phase

N/A

Inclusion and Exclusion Criteria

  • All Individuals:
  • Have been previously diagnosed with MM based on the IMWG 2016 criteria and currently requires treatment.
  • Must have measurable disease as defined by 1 or more of the following:
  • Serum monoclonal protein (M-protein) ≥ 0.5 grams per deciliter (g/dL) (greater than or equal to [≥] 5 grams per liter [g/L]).
  • Urine M-protein ≥ 200 mg/24 hours (h).
  • Serum free light chain (SFLC) assay: involved SFLC level ≥ 10 mg/dL (100 mg/L) with abnormal SFLC ratio.
  • Has provided informed consent.
  • Is willing and able to comply with clinic visits and procedure outlined in the study protocol.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Life expectancy ≥ 3 months.
  • Absolute neutrophil count (ANC) ≥ 1000 cells/uL (1.0 x 10^9/L); granulocyte colony-stimulating factor (G-CSF) is not permitted within 1 week of screening to meet eligibility criteria.
  • Platelet count ≥ 75,000 cells/uL (75 x 10^9/L); platelet transfusion is not permitted within 1 week of screening to meet eligibility criteria.
  • Hemoglobin ≥ 9 g/dL; prior to initial dose of study treatment. NOTE: Transfusions are allowed to meet hemoglobin eligibility
  • Adequate liver function as demonstrated by the following:
  • Aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN).
  • Alanine aminotransferase (ALT) ≤ 3.0 x ULN.
  • Total bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN and primarily unconjugated if individual has a documented history of Gilbert's syndrome or genetic equivalent).
  • International normalized ratio (INR) ≤ 1.2; Individuals receiving anticoagulation treatment may be allowed to participate if INR is within the therapeutic range prior to alternate assignment.
  • Individuals must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min calculated by the Cockcroft-Gault formula or measured by 24 hours urine collection.
  • Corrected serum calcium ≤ 2.9 millimoles per liter (mmol/L) (11.5 mg/dL); measures to reduce calcium to acceptable levels, such as a short course of steroids, bisphosphonates, hydration, or calcitonin are acceptable.
  • Pretreatment blood cross-match completed.
  • Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
  • Must be willing to consent to mandatory pretreatment and on-treatment bone marrow biopsies (trephines).
  • Magrolimab in Combination with Daratumumab: In addition to fulfilling the inclusion criteria for all individuals, individuals who are assigned to receive magrolimab in combination with daratumumab should fulfill the following:
  • Must have received at least 3 previous lines of therapy for MM including an IMiD such as lenalidomide and a PI such as bortezomib.
  • Individuals must have not had prior anti-CD38 antibody therapy for at least 6 months prior to enrollment.
  • No prior history of discontinuation of daratumumab due to toxicity.
  • Magrolimab in Combination with Pomalidomide and Dexamethasone: In addition to fulfilling the inclusion criteria for all Individuals, Individuals who are assigned to receive magrolimab in combination with pomalidomide and dexamethasone should fulfill the following:
  • Must have received at least 3 previous lines of therapy for MM including an IMiD such as lenalidomide and a PI such as bortezomib.
  • Prior treatment with pomalidomide is allowed if the Individual achieved at least a PR to the most recent pomalidomide therapy and will have had at least a 6-month treatment-free interval from the last dose of pomalidomide until first study treatment.
  • No prior history of discontinuation of pomalidomide due to toxicity.
  • No contraindication to dexamethasone.
  • Magrolimab in Combination with Bortezomib and Dexamethasone: In addition to fulfilling the inclusion criteria for all individuals, individuals who are assigned to receive magrolimab in combination with bortezomib and dexamethasone should fulfill the following:
  • Must have received at least 1 previous line of therapy for MM including an IMiD such as lenalidomide and a PI such as bortezomib.
  • Prior treatment with a PI, including bortezomib, is allowed if the Individual achieved at least a PR to the most recent prior PI therapy, and will have had at least a 6-month PI treatment-free interval from the last dose until first study treatment.
  • No prior history of discontinuation of bortezomib due to toxicity.
  • No contraindication to dexamethasone. Key

  • Individuals with known amyloidosis including myeloma complicated by amyloidosis.
  • Multiple myeloma of immunoglobulin M subtype.
  • Individuals with Waldenstrom's macroglobulinemia.
  • Individuals with myelodysplastic syndrome (MDS).
  • Plasma cell leukemia (defined as either 20% of peripheral blood white blood cell (WBC) count comprised of plasma/CD138-positive cells) or circulating plasma cells ≥ 2 x 10^9/L.
  • Individuals with solitary bone or extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
  • Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes (POEMS) syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes).
  • Glucocorticoid therapy (prednisone > 40 mg/day or equivalent) within 14 days prior to enrollment; corticosteroid therapy for hypercalcemia is allowed.
  • Chemotherapy with approved or investigational anticancer therapeutics within 28 days prior to enrollment.
  • Focal radiation therapy within 7 days prior to enrollment; radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to enrollment (ie, prior radiation must have been to less than 30% of the bone marrow).
  • Immunotherapy within 28 days prior to enrollment.
  • Major surgery (excluding procedures to stabilize the vertebrae) within 28 days prior to enrollment.
  • Positive serum pregnancy test.
  • Breastfeeding female.
  • Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient.
  • Prior treatment with CD47 or signal regulatory protein alpha (SIRP

Sites

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