Multiple MyelomaPhase 2NCT04892446
Study of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma
A Phase 2 study testing Magrolimab, Daratumumab and Pomalidomide in people with Multiple Myeloma, run by Gilead Sciences at 22 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Magrolimab, Daratumumab and Pomalidomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 22 sitesin 3 countries
- Study dates
- 9 Nov 2021to 25 Apr 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 42Show fewer
- 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-cluster differentiation 38 (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 partial response (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 Carfilzomib and Dexamethasone: In addition to fulfilling the inclusion criteria for all patients, patients who are assigned to receive magrolimab in combination with carfilzomib and dexamethasone should fulfill the following:
- Patient 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 a PI, including carfilzomib, is allowed if the patient 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 carfilzomib 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.
Who cannot join
- 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.
Show all 33Show fewer
- 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.
Trial locations and contacts
22 sites in 3 countries.
22 sites in 3 countries
United States16 sites
Bend Memorial Clinic, P.C. d/b/a Summit Health
Bend, Oregon, 97701
Roswell Park Cancer Institute
Buffalo, New York, 14263
Levine Cancer Institute
Charlotte, North Carolina, 28204
Cleveland Clinic - Taussig Cancer Institute
Cleveland, Ohio, 44195
The Ohio State University
Columbus, Ohio, 43210
US Oncology, Inc. IRB
Dallas, Texas, 75246
Karmanos Cancer Institute
Detroit, Michigan, 48201
Duke University
Durham, North Carolina, 27710
US Oncology, Inc., IRB
Fairfax, Virginia, 22031
US San Diego Moores Cancer Center
La Jolla, California, 92093
Memorial Sloan Kettering Cancer Center - Main Campus
New York, New York, 10065
Hightower Clinical
Oklahoma City, Oklahoma, 73102
Stanford Cancer Institute
Palo Alto, California, 94305
Oregon Health and Science University
Portland, Oregon, 97239
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Arizona Oncology Associates , PC - HOPE
Tucson, Arizona, 85711
Czechia4 sites
Fakultní nemocnice Brno
Brno, 625 00
Fakultní Nemocnice Olomouc
Olomouc, 779 00
Vseobecna fakultni nemocnice v Praze
Prague, 100 34
Fakultní nemocnice Ostrava
Severomoravsky KRAJ, 708 52
Canada2 sites
Cross Cancer Institute
Edmonton, T6G 1Z2
Princess Margaret Cancer Centre
Toronto, M5G 2M9
About this study
Official title: A Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma
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
- Being tested
- Magrolimab, Daratumumab, Pomalidomide, Dexamethasone, Bortezomib
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MagrolimabDrug
Also called GS-4721
Administered IV
DaratumumabDrug
Administered either SC or IV
PomalidomideDrug
Administered orally
DexamethasoneDrug
Administered orally
BortezomibDrug
Administered either SC or IV
CarfilzomibDrug
Administered IV
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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). Receives: 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). Receives: Drug: Magrolimab; Drug: Dexamethasone; Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 1.5 years
Secondary outcomes (3)
Duration of Response (DoR)
DoR was measured from earliest date of sCR, CR, VGPR, or PR, whichever was first recorded, until earliest date of documented progression disease (PD) per IMWG 2016, documented relapse, or death from any cause, whichever occurred first. sCR, CR, VGPR, or PR are defined in outcome measure #4. PD is having any 1 or more of following criteria: increase of 25% from lowest confirmed response value; increase between involved and uninvolved FLC levels >10 mg/dL; increase in BM plasma-cell ≥10%; appearance of new lesion, ≥ 50% increase in sum of products of 2 longest perpendicular diameters of >1 lesion, or ≥ 50% increase in longest diameter of a previous lesion >1 cm in short axis; ≥ 50% increase in circulating plasma cells. Relapse is new soft tissue plasmacytomas or bone lesions; increase in size of existing plasmacytomas or bone lesions; hypercalcemia (> 11 mg/dL); decrease in hemoglobin of ≥ 2 g/dL; rise in serum creatinine by 2 mg/dL; hyperviscosity. Kaplan Meier estimates were used.
Measured: Up to 1.5 years
Serum Concentration of Magrolimab
Arm 1: Magrolimab+Daratumumab; Arm 2: Magrolimab+Pomalidomide+Dexamethasone; Arm 3: Magrolimab+Carfilzomib+Dexamethasone.
Measured: 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
The percentage of participants who had treatment induced or treatment-boosted anti-drug antibody (ADA) based on participants who had non-missing baseline ADA sample and at least one post-treatment ADA result reported in Immunogenicity Analysis Set. Treatment-Induced ADA: participants who had negative baseline ADA sample and at least one positive post-treatment ADA sample based on participants who had both non-missing baseline and at least one post-treatment ADA result reported. Treatment-Boosted ADA: participants who had positive baseline ADA sample and at least one positive post-treatment ADA sample and the (max titer of the posttreatment ADA) / (titer of baseline ADA) >= 4.
Measured: Up to Day 358
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2021
- Study start9 Nov 2021
- Primary completion25 Apr 2024
- Study completion25 Apr 2024
Why it stopped: This study was terminated early due to the Sponsor's decision to discontinue development of the investigational drug and close the program.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04892446
- Sponsor's protocol ID
- GS-US-558-5915
- Other IDs
- 2021-001798-21
- Status last verified
- Apr 2025
- First submitted
- 14 May 2021
- Last updated
- 2 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36779512Paul 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.
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.
PubMed 40485906
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT04892446
- Acronym / sponsor ID
- GS-US-558-5915
- Conditions
- Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated early due to the Sponsor's decision to discontinue development of the investigational drug and close the program.
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 9 Nov 2021 (actual)
- Primary completion
- 25 Apr 2024 (actual)
- Study completion
- 25 Apr 2024 (actual)
- First posted
- 19 May 2021 (actual)
- Results
- Posted 2 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Magrolimab+Daratumumab | Experimental | Drug: Magrolimab, Drug: DaratumumabParticipants 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). |
| Magrolimab+Pomalidomide+Dexamethasone | Experimental | Drug: Magrolimab, Drug: Pomalidomide, Drug: DexamethasoneParticipants 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). |
| Magrolimab+Carfilzomib+Dexamethasone | Experimental | Drug: Magrolimab, Drug: Dexamethasone, Drug: CarfilzomibParticipants 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). |
| Magrolimab+Bortezomib+Dexamethasone | Experimental | Drug: Magrolimab, Drug: Dexamethasone, Drug: BortezomibBortezomib + 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (42 listed)
- 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:
- 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.
Key exclusion criteria (33 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MagrolimabAlso: GS-4721Administered IV | Drug | Magrolimab+Bortezomib+Dexamethasone, Magrolimab+Carfilzomib+Dexamethasone, Magrolimab+Daratumumab, Magrolimab+Pomalidomide+Dexamethasone |
| DaratumumabAdministered either SC or IV | Drug | Magrolimab+Daratumumab |
| PomalidomideAdministered orally | Drug | Magrolimab+Pomalidomide+Dexamethasone |
| DexamethasoneAdministered orally | Drug | Magrolimab+Bortezomib+Dexamethasone, Magrolimab+Carfilzomib+Dexamethasone, Magrolimab+Pomalidomide+Dexamethasone |
| BortezomibAdministered either SC or IV | Drug | Magrolimab+Bortezomib+Dexamethasone |
| CarfilzomibAdministered IV | Drug | Magrolimab+Carfilzomib+Dexamethasone |
Primary outcome
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
Time frame: Up to 35 days
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.
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAE's) According to the NCI CTCAE Version 5.0
Time frame: Up to 1.3 years plus 70 days
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.
Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0
Time frame: Up to 1.3 years plus 70 days
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.
Objective Response Rate (ORR)
Time frame: Up to 1.5 years
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.
3 secondary outcomes
Duration of Response (DoR)
Time frame: Up to 1.5 years
Serum Concentration of Magrolimab
Time frame: 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
Time frame: Up to Day 358
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 36779512Paul 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.
- BackgroundPaul 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.
- Derived from this study: PubMed 40485906Paul 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.
- Gilead Clinical Trials WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Multiple Myeloma
RecruitingPhase 1
A Study to Examine the Effects of Novel Therapy Linvoseltamab in Combination With Other Cancer Treatments for Adult Participants With Multiple Myeloma That is Resistant to Current Standard of Care Treatments
Multiple Myeloma
RecruitingPhase 2
Cevostamab in Combination With Pomalidomide and Dexamethasone After BCMA- Targeting CAR T-Cell Therapy in Participants With Previously Treated Multiple Myeloma
Multiple Myeloma
RecruitingPhase 1/2
A Study Evaluating the Safety and Efficacy of Multiple Treatments in Participants With Multiple Myeloma
Multiple Myeloma
RecruitingPhase 1/2
A Trial to Study if REGN17372 in Combination With Linvoseltamab is Tolerable for Adult Participants With Relapsed/Refractory Multiple Myeloma
Relapsed Refractory Multiple Myeloma (RRMM)
RecruitingObservational study
Biospecimen Procurement for Center for Immuno-Oncology Immunotherapy Protocols
Multiple Myeloma, Lymphoma, Non-Hodgkin
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
22 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Magrolimab, Daratumumab and Pomalidomide in people with Multiple Myeloma, run by Gilead Sciences at 22 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 42 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Czechia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Up to 35 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04892446, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2025.