Study of Magrolimab Combinations in Participants With Relapsed/Refractory Multiple Myeloma

• Status: Not yet recruiting
• Trial end date: 2023-09-01
• Target enrollment: 0
• Participant gender: All

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: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gilead Sciences
• Treatments: Bortezomib; Daratumumab; Dexamethasone; Magrolimab; Pomalidomide

Criteria

Key Inclusion Criteria:

All Individuals:

• Individual has been previously diagnosed with MM based on the IMWG 2016 criteria and currently requires treatment.

• Individuals 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.

• Individuals must have received at least 3 previous lines of therapy for MM including an IMiD such as lenalidomide and a PI such as bortezomib.

• Individual has provided informed consent.

• Individual 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/dL (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/dL (75 x 10^9/L); platelet transfusion is not permitted within 1 week of screening to meet eligibility criteria.

• Hemoglobin ≥ 9.0 g/dL; no more than 4 units of packed Red blood cells (RBCs) are allowed in the 30 days prior to screening.

• For Individuals with prior cardiac history such as ischemic heart disease, left ventricular ejection fraction ≤ 45%, symptomatic congestive heart failure, New York Heart Association (NYHA) Class III or IV heart failure, or other conditions that may be sensitive to demand ischemia, the hemoglobin must be ≥ 9.5 g/dL prior to initial dose of study treatment. Transfusions are allowed to meet hemoglobin eligibility criterion.

• 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).

• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time ≤ 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.

• Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.

• Individuals 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:

• Individuals must have CD38-positive myeloma and 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:

• 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:

• 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 Exclusion Criteria:

• 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 (SIRPα)-targeting agents.

• Current participation in another interventional clinical trial.

• Autologous stem cell transplant < 100 days prior to enrollment.

• Considered eligible to receive autologous or allogeneic stem cell transplant (SCT) at the time of enrollment.

• Allogeneic SCT for the treatment of MM within 6 months of enrollment or active graft-versus-host disease requiring immunosuppression.

• Significant neuropathy (Grade 3 to 4, or Grade 2 with pain) within 14 days prior to enrollment.

• Known inherited or acquired bleeding disorders.

• Known cirrhosis.

• Clinical suspicion or documentation of central nervous system (CNS) disease.

• Significant disease or medical conditions, as assessed by the investigator and sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, congestive heart failure, or New York Heart Association (NYHA) Class III or IV heart failure.

• Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed against reactivation) or antifungal agents within 14 days prior to enrollment.

• Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which patients are not on active anticancer therapies and have had no evidence of active malignancy for at least 1 year. Other exceptions may be considered with sponsor approval. Previous hormonal therapy with luteinizing hormone-releasing hormone agonists for prostate cancer and treatment with bisphosphonates and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors are not criteria for exclusion.

• Known active or chronic hepatitis B or C infection or human immunodeficiency virus (HIV) infection in medical history.

• Active hepatitis B virus (HBV) and/or active hepatitis C virus (HCV), and/or HIV infection following testing at screening:

• Individuals who test positive for hepatitis B surface antigen (HBsAg). Patients who test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA by quantitative polymerase chain reaction (PCR) for confirmation of active disease.

• Individuals who test positive for HCV antibody. Patients who test positive for HCV antibody will require HCV ribonucleic acid (RNA) by quantitative PCR for confirmation of active disease.

• Individuals who test positive for HIV.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.