Multiple Myeloma
Conditions
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.
Interventions
DRUGMagrolimab
Administered IV
DRUGDaratumumab
Administered either SC or IV
DRUGPomalidomide
Administered orally
DRUGDexamethasone
Administered orally
DRUGBortezomib
Administered either SC or IV
DRUGCarfilzomib
Administered IV
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 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). * 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. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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 | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Arm 1: Magrolimab+Daratumumab; Arm 2: Magrolimab+Pomalidomide+Dexamethasone; Arm 3: Magrolimab+Carfilzomib+Dexamethasone. |
| Percentage of Participants With Positive Anti-magrolimab Antibodies | Up to Day 358 | 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. |
| Duration of Response (DoR) | Up to 1.5 years | 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. |
Countries
Canada, Czechia, United States
Participant flow
Recruitment details
43 participants were screened.
Pre-assignment details
Participants were enrolled at study sites in the United States, Czech Republic, and Canada. Magrolimab in combination with bortezomib and dexamethasone cohort was not initiated due to early closure of study. As all participants were dosed with same dose of magrolimab, per prespecified analysis, data for Safety Run-in and corresponding Dose-expansion cohorts were combined except for dose limiting toxicity outcome measure, for which data was collected only in Safety Run-in Cohorts.
Participants by arm
| Arm | Count |
|---|---|
| Magrolimab+Daratumumab Participants in Safety Run-in and Dose-expansion period with relapsed/refractory multiple myeloma who have had 3 or more prior therapies including an IMiD and a PI received magrolimab IV 1 mg/kg on Day 1 and 30 mg/kg on Days 8, 15, 22, 29 of Cycle 1; 30 mg/kg every week on Days 1, 8, 15, 22 of Cycle 2; 30 mg/kg on Days 1, 15 from Cycle 3 onwards.
Participants also received 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, 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). | 14 |
| Magrolimab+Pomalidomide+Dexamethasone Participants in Safety Run-in and Dose-expansion period with relapsed/refractory multiple myeloma who have had 3 or more prior therapies including an IMiD and a PI received magrolimab IV 1 mg/kg on Day 1 and 30 mg/kg on Days 8, 15, 22, 29 of Cycle 1; 30 mg/kg every week on Days 1, 8, 15, 22 of Cycle 2; 30 mg/kg on Days 1, 15 from Cycle 3 onwards.
Participants also received pomalidomide orally 4 mg on Days 1 to 21 (daily) of Cycle 1 and onward and dexamethasone orally 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). | 10 |
| Magrolimab+Carfilzomib+Dexamethasone Participants in Safety Run-in and Dose-expansion period with relapsed/refractory multiple myeloma who have had 3 or more prior therapies including an IMiD and a PI received magrolimab IV 1 mg/kg on Day 1 and 30 mg/kg on Days 8, 15, 22, 29 of Cycle 1; 30 mg/kg every week on Days 1, 8, 15, 22 of Cycle 2; 30 mg/kg on Days 1, 15 from Cycle 3 onwards.
Participants also received carfilzomib IV 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 was tolerated after Cycle 1, Day 8, the dose was escalated to 70 mg/m\^2 on Cycle 1, Day 15 and thereafter) and dexamethasone orally or IV 40 mg on Days 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). | 11 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 4 | 4 | 0 |
| Overall Study | Investigator's discretion | 1 | 1 | 0 |
| Overall Study | Study terminated by sponsor | 0 | 0 | 2 |
| Overall Study | Withdrew consent | 3 | 0 | 1 |
Baseline characteristics
| Characteristic | Magrolimab+Pomalidomide+Dexamethasone | Magrolimab+Carfilzomib+Dexamethasone | Magrolimab+Daratumumab | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 6 Participants | 7 Participants | 19 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 5 Participants | 7 Participants | 16 Participants |
| Age, Continuous | 66 years STANDARD_DEVIATION 10.2 | 68 years STANDARD_DEVIATION 8 | 65 years STANDARD_DEVIATION 9.5 | 66 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 11 Participants | 14 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 10 Participants | 11 Participants | 30 Participants |
| Region of Enrollment Canada | 1 Participants | 4 Participants | 2 Participants | 7 Participants |
| Region of Enrollment Czechia | 4 Participants | 3 Participants | 2 Participants | 9 Participants |
| Region of Enrollment United States | 5 Participants | 4 Participants | 10 Participants | 19 Participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 10 Participants | 17 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 4 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 15 | 4 / 10 | 0 / 11 |
| other Total, other adverse events | 14 / 14 | 10 / 10 | 11 / 11 |
| serious Total, serious adverse events | 5 / 14 | 5 / 10 | 4 / 11 |
Outcome results
Primary
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.
Time frame: Up to 1.5 years
Population: The Full Analysis Set included all participants who took ≥ 1 dose of study drugs with arm designated according to the planned treatment at enrollment.~As all participants were dosed with same dose of magrolimab, per prespecified analysis, data for Safety Run-in and corresponding Dose-expansion cohorts were combined for all 3 arms.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Magrolimab+Daratumumab | Objective Response Rate (ORR) | 14.3 percentage of participants |
| Magrolimab+Pomalidomide+Dexamethasone | Objective Response Rate (ORR) | 20.0 percentage of participants |
| Magrolimab+Carfilzomib+Dexamethasone | Objective Response Rate (ORR) | 36.4 percentage of participants |
Primary
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.
Time frame: Up to 35 days
Population: The DLT-Evaluable Analysis Set included all participants in the Safety Analysis Set who were enrolled in the Safety Run-in cohorts and fulfilled the criteria for evaluation for DLT specified in the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Magrolimab+Daratumumab | 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 | 16.7 percentage of participants |
| Magrolimab+Pomalidomide+Dexamethasone | 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 | 16.7 percentage of participants |
| Magrolimab+Carfilzomib+Dexamethasone | 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 | 0 percentage of participants |
Primary
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.
Time frame: Up to 1.3 years plus 70 days
Population: The Safety Analysis Set included all participants who received at least 1 dose of study treatment with treatment group designated according to the actual treatment received.~As all participants were dosed with same dose of magrolimab, per prespecified analysis, data for Safety Run-in and corresponding Dose-expansion cohorts were combined for all 3 arms.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Magrolimab+Daratumumab | Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAE's) According to the NCI CTCAE Version 5.0 | 100 percentage of participants |
| Magrolimab+Pomalidomide+Dexamethasone | Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAE's) According to the NCI CTCAE Version 5.0 | 100 percentage of participants |
| Magrolimab+Carfilzomib+Dexamethasone | Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAE's) According to the NCI CTCAE Version 5.0 | 100 percentage of participants |
Primary
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.
Time frame: Up to 1.3 years plus 70 days
Population: Participants in the Safety Analysis Set were analyzed. As all participants were dosed with same dose of magrolimab, per prespecified analysis, data for Safety Run-in and corresponding Dose-expansion cohorts were combined for all 3 arms.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Magrolimab+Daratumumab | Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0 | Hematology: Any Grade 1 or Higher | 92.9 percentage of participants |
| Magrolimab+Daratumumab | Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0 | Chemistry: Any Grade 1 or Higher | 92.9 percentage of participants |
| Magrolimab+Pomalidomide+Dexamethasone | Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0 | Hematology: Any Grade 1 or Higher | 100 percentage of participants |
| Magrolimab+Pomalidomide+Dexamethasone | Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0 | Chemistry: Any Grade 1 or Higher | 100 percentage of participants |
| Magrolimab+Carfilzomib+Dexamethasone | Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0 | Chemistry: Any Grade 1 or Higher | 100 percentage of participants |
| Magrolimab+Carfilzomib+Dexamethasone | Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0 | Hematology: Any Grade 1 or Higher | 100 percentage of participants |
Secondary
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.
Time frame: Up to 1.5 years
Population: Participants in the Full Analysis Set who had objective response were analyzed. Participants who were observed to have documented relapse, documented PD, or death were censored at the date of their last response assessment.~As all participants were dosed with same dose of magrolimab, per prespecified analysis, data for Safety Run-in and corresponding Dose-expansion cohorts were combined for all 3 arms.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Magrolimab+Daratumumab | Duration of Response (DoR) | NA months |
| Magrolimab+Pomalidomide+Dexamethasone | Duration of Response (DoR) | NA months |
| Magrolimab+Carfilzomib+Dexamethasone | Duration of Response (DoR) | NA months |
Secondary
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.
Time frame: Up to Day 358
Population: The Immunogenicity Analysis Set included all enrolled participants who received at least 1 dose of magrolimab and have at least 1 evaluable anti-magrolimab antibody test result.~As all participants were dosed with same dose of magrolimab, per prespecified analysis, data for Safety Run-in and corresponding Dose-expansion cohorts were combined for all 3 arms.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Magrolimab+Daratumumab | Percentage of Participants With Positive Anti-magrolimab Antibodies | 0 percentage of participants |
| Magrolimab+Pomalidomide+Dexamethasone | Percentage of Participants With Positive Anti-magrolimab Antibodies | 0 percentage of participants |
| Magrolimab+Carfilzomib+Dexamethasone | Percentage of Participants With Positive Anti-magrolimab Antibodies | 0 percentage of participants |
Secondary
Serum Concentration of Magrolimab
Arm 1: Magrolimab+Daratumumab; Arm 2: Magrolimab+Pomalidomide+Dexamethasone; Arm 3: Magrolimab+Carfilzomib+Dexamethasone.
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
Population: The Pharmacokinetic Analysis Set included all participants who received ≥ 1 dose of magrolimab and had ≥ 1 measurable posttreatment serum concentration of magrolimab. Participants with available data were analyzed.~As all participants were dosed with same dose of magrolimab, per prespecified analysis, data for Safety Run-in and corresponding Dose-expansion cohorts were combined for all 3 arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Magrolimab+Daratumumab | Serum Concentration of Magrolimab | Predose: Cycle 2 Day 1 | 621000 ng/mL | Standard Deviation 233000 |
| Magrolimab+Daratumumab | Serum Concentration of Magrolimab | Predose: Cycle 1 Day 22 | 435000 ng/mL | Standard Deviation 245000 |
| Magrolimab+Daratumumab | Serum Concentration of Magrolimab | Predose: Cycle 13 Day 1 | 295000 ng/mL | — |
| Magrolimab+Daratumumab | Serum Concentration of Magrolimab | Predose: Cycle 3 Day 1 | 853000 ng/mL | Standard Deviation 399000 |
| Magrolimab+Daratumumab | Serum Concentration of Magrolimab | Anytime: Last sample collection day: Up to Day 358 | 445000 ng/mL | Standard Deviation 337000 |
| Magrolimab+Daratumumab | Serum Concentration of Magrolimab | Predose: Cycle 1 Day 1 | NA ng/mL | — |
| Magrolimab+Daratumumab | Serum Concentration of Magrolimab | Predose: Cycle 4 Day 1 | 694000 ng/mL | Standard Deviation 82700 |
| Magrolimab+Daratumumab | Serum Concentration of Magrolimab | Predose: Cycle 5 Day 1 | 517000 ng/mL | Standard Deviation 186000 |
| Magrolimab+Daratumumab | Serum Concentration of Magrolimab | Predose: Cycle 7 Day 1 | 332000 ng/mL | — |
| Magrolimab+Daratumumab | Serum Concentration of Magrolimab | Predose: Cycle 10 Day 1 | 336000 ng/mL | — |
| Magrolimab+Pomalidomide+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 7 Day 1 | 307000 ng/mL | Standard Deviation 153000 |
| Magrolimab+Pomalidomide+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 2 Day 1 | 713000 ng/mL | Standard Deviation 293000 |
| Magrolimab+Pomalidomide+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 1 Day 1 | NA ng/mL | — |
| Magrolimab+Pomalidomide+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 3 Day 1 | 739000 ng/mL | Standard Deviation 365000 |
| Magrolimab+Pomalidomide+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 1 Day 22 | 303000 ng/mL | Standard Deviation 182000 |
| Magrolimab+Pomalidomide+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 5 Day 1 | 373000 ng/mL | Standard Deviation 142000 |
| Magrolimab+Pomalidomide+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 4 Day 1 | 5540 ng/mL | — |
| Magrolimab+Pomalidomide+Dexamethasone | Serum Concentration of Magrolimab | Anytime: Last sample collection day: Up to Day 358 | 179000 ng/mL | Standard Deviation 131000 |
| Magrolimab+Carfilzomib+Dexamethasone | Serum Concentration of Magrolimab | Anytime: Last sample collection day: Up to Day 358 | 86000 ng/mL | Standard Deviation 34000 |
| Magrolimab+Carfilzomib+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 1 Day 1 | NA ng/mL | — |
| Magrolimab+Carfilzomib+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 1 Day 22 | 421000 ng/mL | Standard Deviation 115000 |
| Magrolimab+Carfilzomib+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 2 Day 1 | 675000 ng/mL | Standard Deviation 274000 |
| Magrolimab+Carfilzomib+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 3 Day 1 | 847000 ng/mL | Standard Deviation 238000 |
| Magrolimab+Carfilzomib+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 4 Day 1 | 459000 ng/mL | Standard Deviation 161000 |
| Magrolimab+Carfilzomib+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 5 Day 1 | 448000 ng/mL | Standard Deviation 90700 |
| Magrolimab+Carfilzomib+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 7 Day 1 | 376000 ng/mL | Standard Deviation 140000 |
| Magrolimab+Carfilzomib+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 10 Day 1 | 361000 ng/mL | Standard Deviation 345000 |
| Magrolimab+Carfilzomib+Dexamethasone | Serum Concentration of Magrolimab | Predose: Cycle 13 Day 1 | 624000 ng/mL | — |