Relapsed or Refractory Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to confirm the safety and tolerability of elranatamab (PF-06863135) in Japanese participants with relapsed or refractory MM.
Interventions
BCMA-CD3 bispecific antibody
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of multiple myeloma (IMWG criteria) * Measurable disease, as defined by at least 1 of the following 1. Serum myeloma (M) protein ≥0.5 g/dL (5 g/L) 2. Urine M protein ≥200 mg/24 h 3. Serum free light chain (FLC) \>100 mg/L (10 mg/dL) with abnormal kappa:lambda ratio * Participants must have progressed on or been intolerant of at least 3 prior therapies including proteasome inhibitor, IMID drug and anti-CD38 antibody, either in combination or as a single agent * ECOG PS 0, 1 or 2. PS 3 is permitted if PS is due solely to bone pain * Adequate bone marrow, hematological, kidney and liver function * Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1 * Not pregnant and willing to use contraception
Exclusion criteria
* POEMS syndrome * Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ * History of active autoimmune disorders * Any form of primary immunodeficiency * History of severe immune-mediated adverse event with prior immunomodulatory treatment * Stem cell transplant within 12 weeks prior to enrollment * Active graft versus host disease other than Grade 1 skin involvement, or that requiring immunosuppressive treatment * Requirement for systemic immune suppressive medication * Active, uncontrolled bacterial, fungal, or viral infection, including HBV, HCV, known HIV or AIDS related illness and SARS-CoV2 * Previous administration with an investigational drug within 4 weeks or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer) * Known or suspected hypersensitivity to component of elranatamab (PF-06863135), murine and bovine products * Live attenuated vaccine within 4 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | Up to 4 weeks | DLT was defined as any of the following: Treatment Emergent Adverse Events (AEs) occurring in Cycle 0 and Cycle 1 (total 4 weeks): Grade (G) 4 neutropenia lasting greater than (\>)7 days; febrile neutropenia (absolute neutrophil count \[ANC\] less than (\<)1,000 per millimeter cube (/mm\^3) with single temperature \>38.3 degree Celsius (deg C), or sustained temperature of greater than or equal to (\>=) 38deg C for \>1 hour \[h\]); G\>=3 neutropenia with infection; G4 thrombocytopenia (unless the baseline count was \>=25,000/mm\^3 and \<50,000/mm\^3, in which case G4 thrombocytopenia was to be accompanied by \>=G2 bleeding), Platelet count \<10,000/mm\^3 was considered a DLT irrespective of other factors; G3 thrombocytopenia with \>=G2 bleeding; G4 AEs; G3 AE \>=5 days despite optimal supportive care (except AEs attributed to cytokine release syndrome \[CRS\]); G3 CRS (except CRS that have not been maximally treated or improved to \<=G1 within 48h); confirmed drug induced liver injury. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 3 or 4, Grade 5 TEAEs and Treatment Related TEAEs Based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5 Except for CRS and ICANS Graded According to ASTCT Grading Criteria 2019 | From first dose of study intervention and up to 90 days after last dose or start of new anticancer therapy (maximum of 65.1 weeks of treatment) | CTCAEv5.0 G3:severe/clinically significant;G4:life-threatening;G5:death.ASTCT CRS G3:temp\>=38degC,hypotension required vasopressor with/without vasopressin and/or hypoxia required high-flow nasal cannula,facemask,nonrebreather mask or venturi mask;G4:temp\>=38degC,hypotension required multiple vasopressors(excluding vasopressin)and/or hypoxia required positive pressure;G5:death.ICANS G3:ICE score0-2,awakens only to tactile stimulus,clinical seizure focal/generalized resolves rapidly or nonconvulsive seizures on electroencephalography resolve with intervention,focal/local edema on neuroimaging;G4:ICEscore 0(unarousable unable to perform ICE),unarousable or requires vigorous/repetitive tactile stimuli to arouse,stupor/coma,life-threatening prolonged seizure(\>5 min),repetitive clinical/electrical seizure without return to baseline,deep focal motor weakness,diffuse cerebral edema on neuroimaging,decerebrate/decorticate posturing,cranial nerve VI palsy,papilledema,Cushing's triad;G5:death. |
| Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Hematology Parameters by NCI CTCAE v 5.0 | From first dose of study intervention and up to 90 days after last dose or start of new anticancer therapy (maximum of 65.1 weeks of treatment) | Hematology parameters that were assessed included: Anemia, Lymphocyte count decreased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased. Abnormalities were graded based on National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 - Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening. |
| Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | From first dose of study intervention and up to 90 days after last dose or start of new anticancer therapy (maximum of 65.1 weeks of treatment) | Chemistry parameters that were assessed included: Alanine aminotransferase increased, Alkaline phosphatase increased, Aspartate aminotransferase increased, Blood bilirubin increased, Creatinine increased, Hypercalcemia, Hyperkalemia, Hypermagnesemia, Hypernatremia, Hypoalbuminemia, Hypocalcemia, Hypoglycemia, Hypokalemia, Hypomagnesemia, Hyponatremia. Abnormalities were graded based on CTCAE version 5.0- Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening. |
| Maximum Observed Serum Concentration (Cmax) of Elranatamab | Cycle 0: from Cycle 0 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days]; Cycle 1: from Cycle 1 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days] | — |
| Time to Maximum Concentration (Tmax) of Elranatamab | Cycle 0: from Cycle 0 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days]; Cycle 1: from Cycle 1 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days] | — |
| Area Under the Concentration-time Profile From Time Zero to the Time Tau (AUCtau) of Elranatamab | Cycle 0: from Cycle 0 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days]; Cycle 1: from Cycle 1 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days] | Area under the concentration-time profile from time zero to the time tau where the dosing interval (tau = 1 week). AUCtau was determined using the linear/log trapezoidal method. |
| Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | At pre-dose on Day 1 of Cycle 0, 3, 4, 5, 6, 7, 8, 12, 16; at pre-dose on Days 1, 8, 15 of Cycle 1 and 2 | — |
| Number of Participants With Anti-drug Antibodies (ADA) of Elranatamab | From the date of first dose up to maximum of 65.1 weeks of treatment | 'A participant was considered ADA positive if baseline titer was missing or negative and participant had \>=1 post-treatment positive titer, or positive titer at baseline and had a \>=4-fold increase in titer from baseline in \>=1 post-treatment sample. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | From first dose of study intervention and up to 90 days after last dose or start of new anticancer therapy (maximum of 65.1 weeks of treatment) | An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. An SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. A TEAE was defined as an AE that first occurred from the first dose of the study intervention until 90 days after the last dose or the day before starting a new anticancer therapy, whichever occurred first. Treatment related AEs and SAEs were defined as AEs and SAEs which was related to the treatment. |
| Number of Participants With Neutralizing Antibodies (NAb) | From the date of first dose up to maximum of 65.1 weeks of treatment | A participant was considered NAb positive if baseline titer was missing or negative and participant had \>=1 post-treatment positive titer, or positive titer at baseline and had a \>=4-fold increase in titer from baseline in \>=1 post-treatment sample. |
| Objective Response Rate (ORR): Percentage of Participants With Objective Response | From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (maximum of 65.1 weeks of treatment) | ORR:% of participants with best overall response; confirmed stringent complete response(sCR),CR, very good partial response(VGPR) or PR per International Myeloma Working Group criteria.sCR: CR& normal serum free light chain(sFLC)ratio &absence of clonal cells in BMB/BMA by immunohistochemistry, immunofluorescence or flow cytometry.CR: negative immunofixation on serum &urine, disappearance of soft tissue plasmacytoma &\<5% plasma cells in BMA, if disease measured by sFLC only,preceding criteria plus normal sFLC ratio.VGPR:Serum & urine M-protein detectable by immunofixation but not on electrophoresis; or \>=90% reduction in serum&urine M-protein level \<100mg/24h.PR:\>=50% reduction in serum M-protein & reduction in 24h urinary M-protein by \>=90% or \<200 mg/24h. If serum & urine M-protein unmeasurable,VGPR & PR: \>=90% &\>=50% decrease in difference respectively between involved & uninvolved sFLC levels & if present at baseline,\>=90% & \>=50% reduction in soft tissue plasmacytomas' size. |
| Time to Response (TTR) | From date of first dose to the first documentation of objective response that is subsequently confirmed (maximum of 65.1 weeks of treatment) | TTR was defined for participants with confirmed objective response (sCR,CR,VGPR and PR) as the time from first date of study intervention to the date of first documentation of objective response. sCR: CR and normal sFLC ratio with absence of clonal cells in BMB/BMA by immunohistochemistry, immunofluorescence or flow cytometry.CR: negative immunofixation on serum and urine,disappearance of soft tissue plasmacytoma, \<5% plasma cells in BMA, if disease measured by sFLC only,preceding criteria plus normal sFLC ratio.VGPR:Serum and urine M-protein detectable by immunofixation but not on electrophoresis; or \>=90% reduction in serum and urine M-protein level \<100mg/24h.PR:\>=50% reduction in serum M-protein and reduction in 24h urinary M-protein by \>=90% or \<200 mg/24h.If serum and urine M-protein unmeasurable,VGPR & PR: \>=90%,\>=50% decrease in difference respectively between involved and uninvolved sFLC levels,if present at baseline,\>=90%, \>=50% reduction in soft tissue plasmacytomas' size. |
| Duration of Response (DOR) | From first documentation of objective response subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurs first, or censoring date (maximum of 65.1 weeks of treatment) | DOR: time from first documentation of objective response subsequently confirmed, until first documentation of confirmed PD or death due to any cause, whichever occurred first. PD= increase of \>=25% from lowest value in \>=1 of following (serum M-protein \[absolute increase \>=0.5g/dL\]; serum M-protein increase \>=1g/dL \[when lowest M-protein \>=5g/dL\]; urine M-protein \[absolute increase \>=200mg/24h\]; participants without measurable serum & urine M-protein levels, difference between involved & uninvolved sFLC levels \[absolute increase \>10mg/dL\]; in participants without measurable serum, urine M-protein levels & involved sFLC levels: bone marrow plasma-cell % irrespective of baseline status \[absolute increase \>=10%\]; appearance of new lesion,\>=50% increase from nadir in SPD of \>1 lesion, or \>=50% increase in longest diameter of previous lesion \>1cm in short axis; \>=50% increase in circulating plasma cells \[\>=200cells/μL\] if this is the only measure of disease. |
| Progression Free Survival (PFS) | From date of first dose until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurs first, or censoring date (maximum of 65.1 weeks of treatment) | Progression free survival (PFS) was the time from the first date of the study intervention to the date of the first documentation of confirmed progression, or death due to any cause. |
| Overall Survival (OS) | From the date of first dose until death due to any cause or censoring date (maximum of 65.1 weeks of treatment) | Overall survival (OS) was the time from the first date of the study intervention to the date of death due to any cause. Participants not known to have died are censored on the date of last known alive. |
| Minimal Residual Disease (MRD) Negativity Rate | From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (maximum of 65.1 weeks of treatment) | MRD negativity rate was defined as percentage of participants with CR or sCR with negative MRD per IMWG sequencing criteria by bone marrow aspirate (BMA). sCR: CR and normal sFLC ratio with absence of clonal cells in BMB/BMA by immunohistochemistry, immunofluorescence or flow cytometry.CR: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytoma and \<5% plasma cells in BMA, if disease measured by sFLC only, preceding criteria plus normal sFLC ratio. MRD was reported at threshold frequency of 10\^5 and 10\^6. |
| Titers of ADA | Cycle1 Day1, Cycle1 Day15, Cycle2 Day1, Cycle3 Day1, Cycle4 Day1, Cycle6 Day1, Cycle8 Day1, Cycle12 Day1, Cycle16 Day1, End of treatment (maximum of 65.1 weeks of treatment) | Titers of ADA at specified timepoints were reported in this outcome measure. |
Countries
Japan
Participant flow
Pre-assignment details
A total of 4 participants were screened and assigned to study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Elranatamab Participants received an initial priming dose of 600 microgram per kilogram elranatamab subcutaneously on Cycle 0 Day 1 (7 days prior to Cycle 1 Day 1). During treatment cycle, participants were administered 1000 microgram per kilogram elranatamab weekly during each cycle (each cycle was of 3 weeks). | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
Baseline characteristics
| Characteristic | Elranatamab |
|---|---|
| Age, Continuous | 64.0 Years STANDARD_DEVIATION 10.03 |
| Race/Ethnicity, Customized Asian | 4 Participants |
| Sex: Female, Male Female | NA Participants |
| Sex: Female, Male Male | NA Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 3 / 4 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
DLT was defined as any of the following: Treatment Emergent Adverse Events (AEs) occurring in Cycle 0 and Cycle 1 (total 4 weeks): Grade (G) 4 neutropenia lasting greater than (\>)7 days; febrile neutropenia (absolute neutrophil count \[ANC\] less than (\<)1,000 per millimeter cube (/mm\^3) with single temperature \>38.3 degree Celsius (deg C), or sustained temperature of greater than or equal to (\>=) 38deg C for \>1 hour \[h\]); G\>=3 neutropenia with infection; G4 thrombocytopenia (unless the baseline count was \>=25,000/mm\^3 and \<50,000/mm\^3, in which case G4 thrombocytopenia was to be accompanied by \>=G2 bleeding), Platelet count \<10,000/mm\^3 was considered a DLT irrespective of other factors; G3 thrombocytopenia with \>=G2 bleeding; G4 AEs; G3 AE \>=5 days despite optimal supportive care (except AEs attributed to cytokine release syndrome \[CRS\]); G3 CRS (except CRS that have not been maximally treated or improved to \<=G1 within 48h); confirmed drug induced liver injury.
Time frame: Up to 4 weeks
Population: Per Protocol Analysis Set included all enrolled participants who had at least 1 dose of study intervention and either experienced DLT or did not have major treatment deviations during the DLT observation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Elranatamab | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Secondary
Area Under the Concentration-time Profile From Time Zero to the Time Tau (AUCtau) of Elranatamab
Area under the concentration-time profile from time zero to the time tau where the dosing interval (tau = 1 week). AUCtau was determined using the linear/log trapezoidal method.
Time frame: Cycle 0: from Cycle 0 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days]; Cycle 1: from Cycle 1 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days]
Population: Pharmacokinetic parameter analysis population was defined as all enrolled participants treated who did not have protocol deviations influencing PK assessment, and had sufficient information to estimate at least 1 of the PK parameters of interest. Here, 'Number Analyzed' signifies participants evaluable at specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Elranatamab | Area Under the Concentration-time Profile From Time Zero to the Time Tau (AUCtau) of Elranatamab | Cycle 0 Day 1 | 21.16 Microgram*day per milliliter | Geometric Coefficient of Variation 42 |
| Elranatamab | Area Under the Concentration-time Profile From Time Zero to the Time Tau (AUCtau) of Elranatamab | Cycle 1 Day 1 | NA Microgram*day per milliliter | — |
Secondary
Duration of Response (DOR)
DOR: time from first documentation of objective response subsequently confirmed, until first documentation of confirmed PD or death due to any cause, whichever occurred first. PD= increase of \>=25% from lowest value in \>=1 of following (serum M-protein \[absolute increase \>=0.5g/dL\]; serum M-protein increase \>=1g/dL \[when lowest M-protein \>=5g/dL\]; urine M-protein \[absolute increase \>=200mg/24h\]; participants without measurable serum & urine M-protein levels, difference between involved & uninvolved sFLC levels \[absolute increase \>10mg/dL\]; in participants without measurable serum, urine M-protein levels & involved sFLC levels: bone marrow plasma-cell % irrespective of baseline status \[absolute increase \>=10%\]; appearance of new lesion,\>=50% increase from nadir in SPD of \>1 lesion, or \>=50% increase in longest diameter of previous lesion \>1cm in short axis; \>=50% increase in circulating plasma cells \[\>=200cells/μL\] if this is the only measure of disease.
Time frame: From first documentation of objective response subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurs first, or censoring date (maximum of 65.1 weeks of treatment)
Population: SAS included all enrolled participants who received at least 1 dose of study intervention. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Elranatamab | Duration of Response (DOR) | 12.70 Months |
Secondary
Maximum Observed Serum Concentration (Cmax) of Elranatamab
Time frame: Cycle 0: from Cycle 0 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days]; Cycle 1: from Cycle 1 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days]
Population: Pharmacokinetic parameter analysis population was defined as all enrolled participants treated who did not have protocol deviations influencing PK assessment and had sufficient information to estimate at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Elranatamab | Maximum Observed Serum Concentration (Cmax) of Elranatamab | Cycle 0 Day1 | 4.382 Micrograms per milliliter | Geometric Coefficient of Variation 33 |
| Elranatamab | Maximum Observed Serum Concentration (Cmax) of Elranatamab | Cycle 1 Day 1 | 8.846 Micrograms per milliliter | Geometric Coefficient of Variation 39 |
Secondary
Minimal Residual Disease (MRD) Negativity Rate
MRD negativity rate was defined as percentage of participants with CR or sCR with negative MRD per IMWG sequencing criteria by bone marrow aspirate (BMA). sCR: CR and normal sFLC ratio with absence of clonal cells in BMB/BMA by immunohistochemistry, immunofluorescence or flow cytometry.CR: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytoma and \<5% plasma cells in BMA, if disease measured by sFLC only, preceding criteria plus normal sFLC ratio. MRD was reported at threshold frequency of 10\^5 and 10\^6.
Time frame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (maximum of 65.1 weeks of treatment)
Population: SAS included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elranatamab | Minimal Residual Disease (MRD) Negativity Rate | Threshold: 10^5 | 25.0 Percentage of participants |
| Elranatamab | Minimal Residual Disease (MRD) Negativity Rate | Threshold: 10^6 | 25.0 Percentage of participants |
Secondary
Number of Participants With Anti-drug Antibodies (ADA) of Elranatamab
'A participant was considered ADA positive if baseline titer was missing or negative and participant had \>=1 post-treatment positive titer, or positive titer at baseline and had a \>=4-fold increase in titer from baseline in \>=1 post-treatment sample.
Time frame: From the date of first dose up to maximum of 65.1 weeks of treatment
Population: Immunogenicity analysis set included all enrolled participants who received at least one dose of study treatment and had at least one sample tested for ADA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Elranatamab | Number of Participants With Anti-drug Antibodies (ADA) of Elranatamab | 2 Participants |
Secondary
Number of Participants With Grade 3 or 4, Grade 5 TEAEs and Treatment Related TEAEs Based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5 Except for CRS and ICANS Graded According to ASTCT Grading Criteria 2019
CTCAEv5.0 G3:severe/clinically significant;G4:life-threatening;G5:death.ASTCT CRS G3:temp\>=38degC,hypotension required vasopressor with/without vasopressin and/or hypoxia required high-flow nasal cannula,facemask,nonrebreather mask or venturi mask;G4:temp\>=38degC,hypotension required multiple vasopressors(excluding vasopressin)and/or hypoxia required positive pressure;G5:death.ICANS G3:ICE score0-2,awakens only to tactile stimulus,clinical seizure focal/generalized resolves rapidly or nonconvulsive seizures on electroencephalography resolve with intervention,focal/local edema on neuroimaging;G4:ICEscore 0(unarousable unable to perform ICE),unarousable or requires vigorous/repetitive tactile stimuli to arouse,stupor/coma,life-threatening prolonged seizure(\>5 min),repetitive clinical/electrical seizure without return to baseline,deep focal motor weakness,diffuse cerebral edema on neuroimaging,decerebrate/decorticate posturing,cranial nerve VI palsy,papilledema,Cushing's triad;G5:death.
Time frame: From first dose of study intervention and up to 90 days after last dose or start of new anticancer therapy (maximum of 65.1 weeks of treatment)
Population: SAS included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Elranatamab | Number of Participants With Grade 3 or 4, Grade 5 TEAEs and Treatment Related TEAEs Based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5 Except for CRS and ICANS Graded According to ASTCT Grading Criteria 2019 | Grade 3 or 4 TEAEs | 2 Participants |
| Elranatamab | Number of Participants With Grade 3 or 4, Grade 5 TEAEs and Treatment Related TEAEs Based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5 Except for CRS and ICANS Graded According to ASTCT Grading Criteria 2019 | Grade 5 TEAEs | 2 Participants |
| Elranatamab | Number of Participants With Grade 3 or 4, Grade 5 TEAEs and Treatment Related TEAEs Based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5 Except for CRS and ICANS Graded According to ASTCT Grading Criteria 2019 | CRS events | 4 Participants |
| Elranatamab | Number of Participants With Grade 3 or 4, Grade 5 TEAEs and Treatment Related TEAEs Based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5 Except for CRS and ICANS Graded According to ASTCT Grading Criteria 2019 | ICANS events | 0 Participants |
Secondary
Number of Participants With Neutralizing Antibodies (NAb)
A participant was considered NAb positive if baseline titer was missing or negative and participant had \>=1 post-treatment positive titer, or positive titer at baseline and had a \>=4-fold increase in titer from baseline in \>=1 post-treatment sample.
Time frame: From the date of first dose up to maximum of 65.1 weeks of treatment
Population: Immunogenicity analysis set included all enrolled participants who received at least one dose of study treatment and had at least one sample tested for ADA. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Elranatamab | Number of Participants With Neutralizing Antibodies (NAb) | 0 Participants |
Secondary
Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0
Chemistry parameters that were assessed included: Alanine aminotransferase increased, Alkaline phosphatase increased, Aspartate aminotransferase increased, Blood bilirubin increased, Creatinine increased, Hypercalcemia, Hyperkalemia, Hypermagnesemia, Hypernatremia, Hypoalbuminemia, Hypocalcemia, Hypoglycemia, Hypokalemia, Hypomagnesemia, Hyponatremia. Abnormalities were graded based on CTCAE version 5.0- Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Time frame: From first dose of study intervention and up to 90 days after last dose or start of new anticancer therapy (maximum of 65.1 weeks of treatment)
Population: SAS included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Alanine aminotransferase increased | 0 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Alkaline phosphatase increased | 0 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Aspartate aminotransferase increased | 0 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Blood bilirubin increased | 0 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Creatinine increased | 0 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Hypercalcemia | 0 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Hyperkalemia | 0 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Hypermagnesemia | 0 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Hypernatremia | 0 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Hypoalbuminemia | 0 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Hypocalcemia | 0 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Hypoglycemia | 0 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Hypokalemia | 1 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Hypomagnesemia | 0 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 | Hyponatremia | 0 Participants |
Secondary
Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Hematology Parameters by NCI CTCAE v 5.0
Hematology parameters that were assessed included: Anemia, Lymphocyte count decreased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased. Abnormalities were graded based on National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 - Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Time frame: From first dose of study intervention and up to 90 days after last dose or start of new anticancer therapy (maximum of 65.1 weeks of treatment)
Population: SAS included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Hematology Parameters by NCI CTCAE v 5.0 | Anemia | 2 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Hematology Parameters by NCI CTCAE v 5.0 | Lymphocyte count decreased | 4 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Hematology Parameters by NCI CTCAE v 5.0 | Neutrophil count decreased | 3 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Hematology Parameters by NCI CTCAE v 5.0 | Platelet count decreased | 0 Participants |
| Elranatamab | Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Hematology Parameters by NCI CTCAE v 5.0 | White blood cell decreased | 3 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs
An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. An SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. A TEAE was defined as an AE that first occurred from the first dose of the study intervention until 90 days after the last dose or the day before starting a new anticancer therapy, whichever occurred first. Treatment related AEs and SAEs were defined as AEs and SAEs which was related to the treatment.
Time frame: From first dose of study intervention and up to 90 days after last dose or start of new anticancer therapy (maximum of 65.1 weeks of treatment)
Population: SAS included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Elranatamab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | TEAEs | 4 Participants |
| Elranatamab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | Treatment Emergent SAEs | 3 Participants |
| Elranatamab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | Treatment Emergent Treatment Related AEs | 4 Participants |
| Elranatamab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | Treatment Emergent Treatment Related SAEs | 3 Participants |
Secondary
Objective Response Rate (ORR): Percentage of Participants With Objective Response
ORR:% of participants with best overall response; confirmed stringent complete response(sCR),CR, very good partial response(VGPR) or PR per International Myeloma Working Group criteria.sCR: CR& normal serum free light chain(sFLC)ratio &absence of clonal cells in BMB/BMA by immunohistochemistry, immunofluorescence or flow cytometry.CR: negative immunofixation on serum &urine, disappearance of soft tissue plasmacytoma &\<5% plasma cells in BMA, if disease measured by sFLC only,preceding criteria plus normal sFLC ratio.VGPR:Serum & urine M-protein detectable by immunofixation but not on electrophoresis; or \>=90% reduction in serum&urine M-protein level \<100mg/24h.PR:\>=50% reduction in serum M-protein & reduction in 24h urinary M-protein by \>=90% or \<200 mg/24h. If serum & urine M-protein unmeasurable,VGPR & PR: \>=90% &\>=50% decrease in difference respectively between involved & uninvolved sFLC levels & if present at baseline,\>=90% & \>=50% reduction in soft tissue plasmacytomas' size.
Time frame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (maximum of 65.1 weeks of treatment)
Population: SAS included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elranatamab | Objective Response Rate (ORR): Percentage of Participants With Objective Response | 50.0 Percentage of participants |
Secondary
Overall Survival (OS)
Overall survival (OS) was the time from the first date of the study intervention to the date of death due to any cause. Participants not known to have died are censored on the date of last known alive.
Time frame: From the date of first dose until death due to any cause or censoring date (maximum of 65.1 weeks of treatment)
Population: SAS included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Elranatamab | Overall Survival (OS) | NA Months |
Secondary
Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab
Time frame: At pre-dose on Day 1 of Cycle 0, 3, 4, 5, 6, 7, 8, 12, 16; at pre-dose on Days 1, 8, 15 of Cycle 1 and 2
Population: Pharmacokinetic concentration population was defined as all enrolled participants who were treated and had at least 1 analyte concentration. Here, 'Number Analyzed' signifies participants evaluable at specific timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 0 Day1: Predose | NA Microgram per milliliter | — |
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 1 Day1: Predose | 4.267 Microgram per milliliter | Geometric Coefficient of Variation 18 |
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 1 Day8: Predose | 8.326 Microgram per milliliter | Geometric Coefficient of Variation 28 |
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 1 Day15: Predose | 12.32 Microgram per milliliter | Geometric Coefficient of Variation 34 |
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 2 Day1: Predose | 13.40 Microgram per milliliter | Geometric Coefficient of Variation 27 |
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 2 Day8: Predose | 16.26 Microgram per milliliter | Geometric Coefficient of Variation 43 |
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 2 Day15: Predose | 17.83 Microgram per milliliter | Geometric Coefficient of Variation 45 |
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 3 Day1: Predose | 19.75 Microgram per milliliter | Geometric Coefficient of Variation 49 |
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 4 Day1: Predose | 21.68 Microgram per milliliter | Geometric Coefficient of Variation 35 |
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 5 Day1: Predose | 21.71 Microgram per milliliter | Geometric Coefficient of Variation 43 |
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 6 Day1: Predose | 23.99 Microgram per milliliter | Geometric Coefficient of Variation 34 |
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 7 Day1: Predose | 18.03 Microgram per milliliter | Geometric Coefficient of Variation 87 |
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 8 Day1: Predose | 24.27 Microgram per milliliter | Geometric Coefficient of Variation 51 |
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 12 Day1: Predose | 21.30 Microgram per milliliter | Geometric Coefficient of Variation 41 |
| Elranatamab | Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab | Cycle 16 Day1: Predose | NA Microgram per milliliter | — |
Secondary
Progression Free Survival (PFS)
Progression free survival (PFS) was the time from the first date of the study intervention to the date of the first documentation of confirmed progression, or death due to any cause.
Time frame: From date of first dose until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurs first, or censoring date (maximum of 65.1 weeks of treatment)
Population: SAS included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Elranatamab | Progression Free Survival (PFS) | NA Months |
Secondary
Time to Maximum Concentration (Tmax) of Elranatamab
Time frame: Cycle 0: from Cycle 0 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days]; Cycle 1: from Cycle 1 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days]
Population: Pharmacokinetic parameter analysis population was defined as all enrolled participants treated who did not have protocol deviations influencing PK assessment and had sufficient information to estimate at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Elranatamab | Time to Maximum Concentration (Tmax) of Elranatamab | Cycle 0 Day 1 | 7.00 Days |
| Elranatamab | Time to Maximum Concentration (Tmax) of Elranatamab | Cycle 1 Day 1 | 2.98 Days |
Secondary
Time to Response (TTR)
TTR was defined for participants with confirmed objective response (sCR,CR,VGPR and PR) as the time from first date of study intervention to the date of first documentation of objective response. sCR: CR and normal sFLC ratio with absence of clonal cells in BMB/BMA by immunohistochemistry, immunofluorescence or flow cytometry.CR: negative immunofixation on serum and urine,disappearance of soft tissue plasmacytoma, \<5% plasma cells in BMA, if disease measured by sFLC only,preceding criteria plus normal sFLC ratio.VGPR:Serum and urine M-protein detectable by immunofixation but not on electrophoresis; or \>=90% reduction in serum and urine M-protein level \<100mg/24h.PR:\>=50% reduction in serum M-protein and reduction in 24h urinary M-protein by \>=90% or \<200 mg/24h.If serum and urine M-protein unmeasurable,VGPR & PR: \>=90%,\>=50% decrease in difference respectively between involved and uninvolved sFLC levels,if present at baseline,\>=90%, \>=50% reduction in soft tissue plasmacytomas' size.
Time frame: From date of first dose to the first documentation of objective response that is subsequently confirmed (maximum of 65.1 weeks of treatment)
Population: SAS included all enrolled participants who received at least 1 dose of study intervention. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Elranatamab | Time to Response (TTR) | 1.396 Months |
Secondary
Titers of ADA
Titers of ADA at specified timepoints were reported in this outcome measure.
Time frame: Cycle1 Day1, Cycle1 Day15, Cycle2 Day1, Cycle3 Day1, Cycle4 Day1, Cycle6 Day1, Cycle8 Day1, Cycle12 Day1, Cycle16 Day1, End of treatment (maximum of 65.1 weeks of treatment)
Population: Immunogenicity analysis set included all enrolled participants who received at least one dose of study treatment and had at least one sample tested for ADA. Here, 'Number of Participants Analyzed' signifies ADA positive participants with at least one evaluable sample. 'Number Analyzed' signifies participants with non-missing ADA titers at each time point.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Elranatamab | Titers of ADA | Cycle12 Day1 | NA Titers |
| Elranatamab | Titers of ADA | End of treatment | NA Titers |
| Unknown | Titers of ADA | Cycle16 Day1 | — Titers |
| Unknown | Titers of ADA | Cycle1 Day1 | — Titers |
| Unknown | Titers of ADA | Cycle1 Day15 | — Titers |
| Unknown | Titers of ADA | Cycle6 Day1 | — Titers |
| Unknown | Titers of ADA | Cycle3 Day1 | — Titers |
| Unknown | Titers of ADA | Cycle4 Day1 | — Titers |
| Unknown | Titers of ADA | Cycle2 Day1 | — Titers |
| Unknown | Titers of ADA | Cycle8 Day1 | — Titers |