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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04892446
Recruitment Status : Recruiting
First Posted : May 19, 2021
Last Update Posted : January 6, 2023
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE May 14, 2021
First Posted Date  ICMJE May 19, 2021
Last Update Posted Date January 6, 2023
Actual Study Start Date  ICMJE November 9, 2021
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2021)
  • Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (Safety Run-in Cohorts) [ Time Frame: First dose date up to the end of the first dosing cycle (Cycle 1=35 days) ]
    A DLT is defined as any Grade 3 or higher hematologic toxicity or Grade 3 or higher nonhematologic toxicity (with some pre-specified exceptions), that has worsened in severity from pretreatment baseline during the DLT assessment period and, in the opinion of the investigator, the adverse event (AE) is at least possibly related to magrolimab.
  • Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAE's) According to the NCI CTCAE Version 5.0 (Safety Run-in Cohorts) [ Time Frame: From date of first dose of any study drug up to the date of last dose of any study drug plus 30 days (Up to 2.5 years) ]
    A treatment-emergent AE will be defined as any AE that begins on or after the date of first dose of any study drug up to the date of last dose of any study drug plus 30 days.
  • Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0 (Safety Run-in Cohorts) [ Time Frame: From baseline to the date of last dose of any study drug plus 30 days (Up to 2.5 years) ]
    Treatment-emergent laboratory abnormalities will be defined as values that increase at least 1 toxicity grade from baseline to the date of last dose of any study drug plus 30 days. If baseline data are missing, then any graded abnormality (ie, at least Grade 1) will be considered a treatment-emergent abnormality.
  • Objective Response Rate (ORR) (Dose Expansion Cohorts) [ Time Frame: Up to 2.5 years ]
    Objective response rate is defined as the percentage of participants who achieve stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) per the International Myeloma Working Group (IMWG) 2016 criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2021)
  • Percentage of Participants Experiencing TEAE's According to the NCI CTCAE Version 5.0 (Dose Expansion Cohorts) [ Time Frame: From date of first dose of any study drug up to the date of last dose of any study drug plus 30 days. (Up to 2.5 years) ]
    A treatment-emergent AE will be defined as any AE that begins on or after the date of first dose of any study drug up to the date of last dose of any study drug plus 30 days.
  • Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0 (Dose Expansion Cohorts) [ Time Frame: From baseline to the date of last dose of any study drug plus 30 days (Up to 2.5 years) ]
    Treatment-emergent laboratory abnormalities will be defined as values that increase at least 1 toxicity grade from baseline to the date of last dose of any study drug plus 30 days. If baseline data are missing, then any graded abnormality (ie, at least Grade 1) will be considered a treatment-emergent abnormality.
  • Duration of Response (Dose Expansion Cohorts) [ Time Frame: Up to 2.5 years ]
    Duration of response is measured from the earliest date of sCR, CR, VGPR, or PR, whichever is first recorded, until the earliest date of documented progression disease (PD), documented relapse, or death from any cause, whichever occurs first. Those who are not observed to have documented relapse, documented PD, or death will be censored at the date of their last response assessment per International Myeloma Working Group (IMWG) 2016 criteria.
  • Progression-free Survival (Dose Expansion Cohorts) [ Time Frame: Up to 2.5 years ]
    Progression-free survival is defined as the duration from the date of the first dose of study treatment to the earliest date of documented relapse, documented PD, or death from any cause, whichever occurs first. Those who are not observed to have documented relapse, documented PD, or death from any cause during the study will be censored at the date of their last response assessment during the study per IMWG 2016 criteria.
  • Overall Survival (Dose Expansion Cohorts) [ Time Frame: Up to 2.5 years ]
    Overall survival is measured from the date of the first dose of study treatment to the date of death from any cause. Those who are not observed to die during the study will be censored at last date they are known to be alive.
  • Serum Concentrations of Magrolimab (Dose Expansion Cohorts) [ Time Frame: Up to end of treatment (approximately 2.5 years) ]
  • Antidrug Antibody (ADA) Against Magrolimab (Dose Expansion Cohorts) [ Time Frame: Up to end of treatment (approximately 2.5 years) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Magrolimab Combinations in Participants With Relapsed/Refractory Multiple Myeloma
Official Title  ICMJE A Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma
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).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Biological: Magrolimab
    Administered IV
    Other Name: GS-4721
  • Drug: Daratumumab
    Administered either SC or IV
  • Drug: Pomalidomide
    Administered orally
  • Drug: Dexamethasone
    Administered orally
  • Drug: Bortezomib
    Administered either SC or IV
  • Drug: Carfilzomib
    Administered IV
Study Arms  ICMJE
  • Experimental: Safety Run-in Cohort (Magrolimab+Daratumumab)

    Participants with relapsed/refractory multiple myeloma who have had 3 or more prior therapies including an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI) will receive magrolimab as per protocol and daratumumab 1800 mg subcutaneously (SC) or 16 milligrams per kilogram (mg/kg) intravenously (IV) on Days 8, 15, 22, 29 of Cycle 1, Days 1, 8, 15, 22 of Cycle 2 and Days 1 and 15 (every 2 weeks) until Cycle 6 (total of 8 doses) followed by Day 1 (every 4 weeks) for subsequent cycles. (Cycle 1=35 days, All other Cycles=28 days)

    .

    Interventions:
    • Biological: Magrolimab
    • Drug: Daratumumab
  • Experimental: Safety Run-in Cohort (Magrolimab+Pomalidomide+Dexamethasone)
    Participants with relapsed/refractory MM who have had 3 or more prior therapies including an IMiD and a PI will receive magrolimab as per protocol and pomalidomide 4 mg on Days 1 to 21 (daily) of Cycle 1, Days 1 to 21 (daily) of Cycle 2 and onward and dexamethasone 40 mg on Days 1, 8, 15, 22, 29 of Cycle 1, Days 1, 8, 15, 22 of Cycle 2 and onward. (Cycle 1=35 days, All other Cycles=28 days)
    Interventions:
    • Biological: Magrolimab
    • Drug: Pomalidomide
    • Drug: Dexamethasone
  • Experimental: Safety Run-in Cohort (Magrolimab+Carfilzomib+Dexamethasone)
    Participants with relapsed/refractory multiple myeloma who have had 3 or more prior therapies including an IMiD and a PI will receive magrolimab as per protocol and carfilzomib 20 mg/m^2 on Days 8, 15, 22 of Cycle 1, Days 1, 8, 15 of Cycle 2 and onward (if the carfilzomib starting dose of 20 mg/m^2 is tolerated after Cycle 1, Day 8, the dose will be escalated to 70 mg/m^2 on Cycle 1, Day 15 and thereafter) and dexamethasone 40 mg on Days 1, 8, 15, 22, 29 of Cycle 1, Days 1, 8, 15, 22 of Cycles 2 to 9 and then Days 1, 8, 15 from Cycle 10 and onward. (Cycle 1=35 days, All other Cycles=28 days)
    Interventions:
    • Biological: Magrolimab
    • Drug: Dexamethasone
    • Drug: Carfilzomib
  • Experimental: Safety Run-in Cohort (Magrolimab+Bortezomib+Dexamethasone)

    Bortezomib + Dexamethasone may be initiated based on the preliminary safety and efficacy of the Carfilzomib + Dexamethasone cohort.

    Participants with relapsed/refractory multiple myeloma who have had 1 or more prior therapies including an IMiD and a PI will receive magrolimab as per protocol and carfilzomib 1.3 mg/m^2 on Days 8, 15, 22, 29 of Cycle 1, Days 1, 8, 15, 22 of Cycle 2 and onward (Maximum of 8 cycles in those who have previously received bortezomib) and dexamethasone 40 mg on Days 1, 8, 15, 22, 29 of Cycle 1, Days 1, 8, 15, 22 of Cycles 2 to 9 and then Days 1, 8, and 15 from Cycle 10 and onward. (Cycle 1=35 days, All other Cycles=28 days)

    Interventions:
    • Biological: Magrolimab
    • Drug: Dexamethasone
    • Drug: Bortezomib
  • Experimental: Dose Expansion Cohort (Magrolimab+Daratumumab)
    Participants with relapsed/refractory multiple myeloma who have had 3 or more prior therapies including an IMiD and a PI will receive magrolimab at the RP2D determined in the Safety Run-in Cohort and daratumumab 1800 mg SC or 16 mg/kg IV on Days 8, 15, 22, 29 of Cycle 1, Days 1, 8, 15, 22 of Cycle 2 and Days 1 and 15 (every 2 weeks) until Cycle 6 (total of 8 doses) followed by Day 1 (every 4 weeks) for subsequent cycles. (Cycle 1=35 days, All other Cycles=28 days)
    Interventions:
    • Biological: Magrolimab
    • Drug: Daratumumab
  • Experimental: Dose Expansion Cohort (Magrolimab+Pomalidomide+Dexamethasone)
    Participants with relapsed/refractory MM who have had 3 or more prior therapies including an IMiD and a PI will receive magrolimab as per protocol and pomalidomide 4 mg on Days 1 to 21 (daily) of Cycle 1, Days 1 to 21 (daily) of Cycle 2 and onward and dexamethasone 40 mg on Days 1, 8, 15, 22, 29 of Cycle 1, Days 1, 8, 15, 22 of Cycle 2 and onward. (Cycle 1=35 days, All other Cycles=28 days)
    Interventions:
    • Biological: Magrolimab
    • Drug: Pomalidomide
    • Drug: Dexamethasone
  • Experimental: Dose Expansion Cohort (Magrolimab+Carfilzomib+Dexamethasone)
    Participants with relapsed/refractory multiple myeloma who have had 3 or more prior therapies including an IMiD and a PI will receive magrolimab at the RP2D determined in the Safety Run-in Cohort and carfilzomib 20 mg/m^2 on Days 8, 15, 22 of Cycle 1, Days 1, 8, 15 of Cycle 2 and onward (if the carfilzomib starting dose of 20 mg/m^2 is tolerated after Cycle 1, Day 8, the dose will be escalated to 70 mg/m^2 on Cycle 1, Day 15 and thereafter) and dexamethasone 40 mg on Days 1, 8, 15, 22, 29 of Cycle 1, Days 1, 8, 15, 22 of Cycles 2 to 9 and then Days 1, 8, 15 from Cycle 10 and onward. (Cycle 1=35 days, All other Cycles=28 days)
    Interventions:
    • Biological: Magrolimab
    • Drug: Dexamethasone
    • Drug: Carfilzomib
  • Experimental: Dose Expansion Cohort (Magrolimab+Bortezomib+Dexamethasone)

    Bortezomib + Dexamethasone may be initiated based on the preliminary safety and efficacy of the Carfilzomib + Dexamethasone cohort.

    Participants with relapsed/refractory multiple myeloma who have had 1 or more prior therapies including an IMiD and a PI will receive magrolimab at the RP2D determined in the Safety Run-in Cohort and bortezomib 1.3 mg/m^2 on Days 8, 15, 22, 29 of Cycle 1, Days 1, 8, 15, 22 of Cycle 2 and onward (Maximum of 8 cycles in those who have previously received bortezomib) and dexamethasone 40 mg on Days 1, 8, 15, 22, 29 of Cycle 1, Days 1, 8, 15, 22 of Cycles 2 to 9 and then Days 1, 8, and 15 from Cycle 10 and onward. (Cycle 1=35 days, All other Cycles=28 days)

    Interventions:
    • Biological: Magrolimab
    • Drug: Dexamethasone
    • Drug: Bortezomib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 14, 2021)
153
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion 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 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gilead Clinical Study Information Center 1-833-445-3230 (GILEAD-0) GileadClinicalTrials@gilead.com
Listed Location Countries  ICMJE Canada,   Czechia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04892446
Other Study ID Numbers  ICMJE GS-US-558-5915
2021-001798-21 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Gilead Sciences
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Gilead Sciences
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP