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

NCT04892446 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-558-59152021-001798-21
• Study Type: interventional
• Target: 36
• Locations: 3 countries
• Sites: 22

Brief Summary

The goal of this clinical study is to learn more about the safety and dosing of the study drug, magrolimab, in combination with other anticancer therapies in participants with relapsed/refractory multiple myeloma.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (4)

• 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

  A DLT was defined as any Grade 3 or higher hematologic toxicity or Grade 3 or higher nonhematologic toxicity, that had worsened in severity from pretreatment baseline during the DLT assessment period and, in the opinion of the investigator, the adverse event (AE) was at least possibly related to magrolimab. Percentages are rounded off.

  Up to 35 days

• Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAE's) According to the NCI CTCAE Version 5.0

  An AE is any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not the AE is considered related to the study drug. A treatment-emergent AE was defined as any AE that began on or after the date of first dose of any study drug up to the date of last dose of any study drug plus 70 days.

  Up to 1.3 years plus 70 days

• Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0

  Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and included the date of last dose of study drug plus 70 days for participants who permanently discontinued study drug, or the day before initiation of new anticancer therapy including stem cell transplant (SCT) (whichever was earlier). If the relevant baseline laboratory value was missing, any abnormality of at least Grade 1 observed within the time frame specified above was considered treatment emergent. Percentages are rounded off.

  Up to 1.3 years plus 70 days

• Objective Response Rate (ORR)

  Objective response rate is defined as the percentage of participants who achieve confirmed stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR), as assessed by the investigator per the International Myeloma Working Group (IMWG) 2016 criteria. CR defined as negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow (BM) aspirates; sCR defined as CR as above plus normal serum free light-chain (FLC) assay ratio and absence of clonal cells in BM biopsy by immunohistochemistry; VGPR defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein plus urine M-protein \<100 mg/24 h; PR defined as ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 h. Percentages are rounded off.

  Up to 1.5 years

Secondary Outcomes (3)

• Duration of Response (DoR)

  Up to 1.5 years

• Serum Concentration of Magrolimab

  Arm 1, 2, 3: Predose: Days 1 and 22 of Cycle 1, Day 1 of Cycles 2, 3, 4, 5, 7, and on last sample collection day (anytime; up to Day 358); Arm 1 and 3: Predose: Day 1 of Cycles 10 and 13

• Percentage of Participants With Positive Anti-magrolimab Antibodies

  Up to Day 358

Study Arms (4)

Magrolimab+Daratumumab

EXPERIMENTAL

Participants with relapsed/refractory multiple myeloma (MM) 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).

Drug: Magrolimab; Drug: Daratumumab

Magrolimab+Pomalidomide+Dexamethasone

EXPERIMENTAL

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 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).

Drug: Magrolimab; Drug: Pomalidomide; Drug: Dexamethasone

Magrolimab+Carfilzomib+Dexamethasone

EXPERIMENTAL

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).

Drug: Magrolimab; Drug: Dexamethasone; Drug: Carfilzomib

Magrolimab+Bortezomib+Dexamethasone

EXPERIMENTAL

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).

Drug: Magrolimab; Drug: Dexamethasone; Drug: Bortezomib

Interventions

Magrolimab DRUG

Administered IV

Also known as: GS-4721

Magrolimab+Bortezomib+Dexamethasone; Magrolimab+Carfilzomib+Dexamethasone; Magrolimab+Daratumumab; Magrolimab+Pomalidomide+Dexamethasone

Daratumumab DRUG

Administered either SC or IV

Magrolimab+Daratumumab

Pomalidomide DRUG

Administered orally

Magrolimab+Pomalidomide+Dexamethasone

Dexamethasone DRUG

Administered orally

Magrolimab+Bortezomib+Dexamethasone; Magrolimab+Carfilzomib+Dexamethasone; Magrolimab+Pomalidomide+Dexamethasone

Bortezomib DRUG

Administered either SC or IV

Magrolimab+Bortezomib+Dexamethasone

Carfilzomib DRUG

Administered IV

Magrolimab+Carfilzomib+Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Individuals:
• Have been previously diagnosed with MM based on the International Myeloma Working Group (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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (22)

Arizona Oncology Associates , PC - HOPE

Tucson, Arizona, 85711, United States

Location

US San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Stanford Cancer Institute

Palo Alto, California, 94305, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center - Main Campus

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic - Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Hightower Clinical

Oklahoma City, Oklahoma, 73102, United States

Location

Bend Memorial Clinic, P.C. d/b/a Summit Health

Bend, Oregon, 97701, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

US Oncology, Inc. IRB

Dallas, Texas, 75246, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

US Oncology, Inc., IRB

Fairfax, Virginia, 22031, United States

Location

Cross Cancer Institute

Edmonton, T6G 1Z2, Canada

Location

Princess Margaret Cancer Centre

Toronto, M5G 2M9, Canada

Location

Fakultní nemocnice Brno

Brno, 625 00, Czechia

Location

Fakultní Nemocnice Olomouc

Olomouc, 779 00, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 100 34, Czechia

Location

Fakultní nemocnice Ostrava

Severomoravsky KRAJ, 708 52, Czechia

Location

Related Publications (3)

• Paul B, Liedtke M, Khouri J, Rifkin R, Gandhi MD, Kin A, Levy MY, Silbermann R, Cottini F, Sborov DW, Sandhu I, Villarreal L, Murphy M, Gu L, Chen A, Rajakumaraswamy N, Usmani SZ. A phase II multi-arm study of magrolimab combinations in patients with relapsed/refractory multiple myeloma. Future Oncol. 2023 Jan;19(1):7-17. doi: 10.2217/fon-2022-0975. Epub 2023 Feb 13.

  PMID: 36779512 BACKGROUND

• Paul B, Minarik J, Cottini F, Gasparetto C, Khouri J, Gandhi M, et al. Safety and Tolerability of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma: Safety Run-in Results From a Phase 2 Study [Poster 3383]. 65th American Society of Hematology (ASH) Annual Meeting; 2023 December 9-12; San Diego, California.

  BACKGROUND

• Paul B, Minarik J, Cottini F, Gasparetto C, Khouri J, Gandhi M, Hillengass J, Levy M, Liedtke M, Manda S, Sandhu I, Sborov D, Spicka I, Usmani S, Dong M, Gu L, Leung C, Doshi P, Chen C, Pour L. Final Results of a Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma. EJHaem. 2025 Jun 6;6(3):e70072. doi: 10.1002/jha2.70072. eCollection 2025 Jun.

  PMID: 40485906 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Multiple Myeloma

Interventions

magrolimab; daratumumab; pomalidomide; Dexamethasone; Bortezomib; carfilzomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

This study was terminated early due to the Sponsor's decision to discontinue development of the investigational drug and program closure. Due to early termination of the study, reported findings should be interpreted in the context of the study's early closure.

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2021
• First Posted: May 19, 2021
• Study Start: November 9, 2021
• Primary Completion: April 25, 2024
• Study Completion: April 25, 2024
• Last Updated: May 2, 2025
• Results First Posted: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (4); US (16); CA (2)