Multiple Myeloma
Conditions
Keywords
Myeloma, Multiple Myeloma, relapsed Multiple Myeloma, refractory Multiple Myeloma, PF-06863135, BCMA, bispecific, bispecific antibody, BCMA-CD3 bispecific, Elranatamab, MagnetisMM-3
Brief summary
The purpose of the study is to evaluate whether single-agent Elranatamab (PF-06863135) can provide clinical benefit in participants with relapsed/refractory multiple myeloma. Elranatamab is a bispecific antibody: binding of Elranatamab to CD3-expressing T-cells and BCMA-expressing multiple myeloma cells causes targeted T-cell-mediated cytotoxicity.
Interventions
BCMA-CD3 bispecific antibody
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of multiple myeloma (IMWG criteria, Rajkumar et al, 2014) * Measurable disease, as defined by at least 1 of the following: 1. Serum M-protein \>0.5 g/dL by SPEP 2. Urinary M-protein excretion \>200 mg/24 hours by UPEP 3. Serum immunoglobulin FLC≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio * Refractory to at least one IMiD * Refractory to at least one PI * Refractory to at least one anti-CD38 antibody * Relapsed/refractory to last anti-myeloma regimen * Cohort A: has not received prior BCMA-directed therapy * Cohort B: has received prior BCMA-directed therapy (ADC or CAR T cells) * ECOG performance status ≤2 * Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1 * Not pregnant and willing to use contraception
Exclusion criteria
* Smoldering multiple myeloma * Active Plasma cell leukemia * Amyloidosis * POEMS syndrome * Stem cell transplant within 12 weeks prior to enrollment * Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection * 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. * Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) as Per International Myeloma Working Group (IMWG) Criteria | From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 16 months) | ORR: % of participants with best overall response of confirmed stringent complete response (sCR), CR, very good partial response (VGPR) or PR per IMWG criteria. sCR: CR & normal serum free light chain (sFLC) ratio & absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytoma & \<5% plasma cells in BMA, if disease measurable 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 M-protein & 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 were 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort A Only: Objective Response Rate as Per IMWG Criteria by BICR for Participants With Extramedullary Disease (EMD) at Baseline | From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 16 months) | ORR: % of participants with best overall response of confirmed stringent complete response (sCR), CR, very good partial response (VGPR) or PR per IMWG criteria. sCR: CR & normal serum free light chain (sFLC) ratio & absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytoma & \<5% plasma cells in BMA, if disease measurable 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 M-protein & 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 were 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. |
| Cohort A Only: Objective Response Rate as Per IMWG Criteria by BICR for Participants Without EMD at Baseline | From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 16 months) | ORR: % of participants with best overall response of confirmed stringent complete response (sCR), CR, very good partial response (VGPR) or PR per IMWG criteria. sCR: CR & normal serum free light chain (sFLC) ratio & absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytoma & \<5% plasma cells in BMA, if disease measurable 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 M-protein & 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 were 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. |
| Duration of Response (DOR) as Per IMWG Criteria by BICR | From first documentation of objective response subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months) | 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. |
| Duration of Response as Per IMWG Criteria by Investigator Assessment | From first documentation of objective response subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months) | 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. |
| Complete Response Rate (CRR) as Per IMWG Criteria by BICR | From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 20.14 months) | CRR: % of participants with BOR of confirmed sCR/CR per IMWG criteria. sCR: CR & normal serum free light chain (sFLC) ratio & absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytoma & \<5% plasma cells in BMA, if disease measurable by sFLC only, preceding criteria plus normal sFLC ratio. |
| Complete Response Rate as Per IMWG Criteria by Investigator Assessment | From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 20.14 months) | CRR: % of participants with BOR of confirmed sCR/CR per IMWG criteria. sCR: CR & normal serum free light chain (sFLC) ratio & absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytoma & \<5% plasma cells in BMA, if disease measurable by sFLC only, preceding criteria plus normal sFLC ratio. |
| Objective Response Rate as Per IMWG Criteria by Investigator Assessment | From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 20.14 months) | ORR: % of participants with best overall response of confirmed stringent complete response (sCR), CR, very good partial response (VGPR) or PR per IMWG criteria. sCR: CR & normal serum free light chain (sFLC) ratio & absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytoma & \<5% plasma cells in BMA, if disease measurable 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 M-protein & 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 were 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. |
| Duration of Complete Response (DOCR) as Per IMWG Criteria by BICR | From first documentation of sCR/CR subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months) | DOCR: time from first documentation of sCR/CR 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. |
| Duration of Complete Response (DOCR) as Per IMWG Criteria by Investigator Assessment | From first documentation of objective sCR/CR subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months) | DOCR: time from first documentation of sCR/CR 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) as Per IMWG Criteria by BICR | From date of first dose until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months) | PFS was defined as the time from the date of first dose until 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. |
| Minimal Residual Disease (MRD) Negativity Rate Per IMWG Sequencing Criteria | From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 20.14 months) | MRD negativity rate was the percentage of participants with CR/sCR and with negative MRD per IMWG sequencing criteria. |
| Overall Survival (OS) | From the date of first dose until death due to any cause. Participants not known to have died were censored on the date of last known alive (up to approximately 20.14 months) | Overall survival (OS) was defined as the time from the date of first dose until death due to any cause. |
| Time-to-Response (TTR) as Per IMWG Criteria by BICR | From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 16 months) | TTR was defined, for participants with an objective response per IMWG criteria, as the time from the date of first dose to the first documentation of objective response that was subsequently confirmed. |
| Time-to-Response (TTR) as Per IMWG Criteria by Investigator Assessment | From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 20.14 months) | TTR was defined, for participants with an objective response per IMWG criteria, as the time from the date of first dose to the first documentation of objective response that was subsequently confirmed. |
| Number of Participants With Treatment Emergent Adverse Events (TEAE) Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 20.14 months) | An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered treatment-emergent relative to study intervention if the adverse event start date was during the on-treatment period (i.e. the time from the first dose of study intervention through the minimum of 90 days after last dose, or \[start day of new anticancer therapy - 1 day\]). CTCAE version 5.0 Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening; Grade 5: death. |
| Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Laboratory Parameters by NCI CTCAE v 5.0 | From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 20.14 months) | CTCAE version 5.0 Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening. |
| Number of Participants With Cytokine Release Syndrome (CRS) Graded According to American Society for Transplantation and Cellular Therapy (ASTCT) Criteria | From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 20.14 months) | CRS Grade 1: temperature \>=38°C without hypotension or hypoxia; Grade 2: temperature \>=38°C with hypotension not requiring vasopressors, and/or hypoxia requiring low-flow nasal cannula, facemask or blow-by; Grade 3: temperature \>=38°C with hypotension requiring a vasopressor with or without vasopressin and/or hypoxia requiring high-flow nasal cannula, facemask, nonrebreather mask, or Venturi mask; Grade 4: temperature \>=38°C with hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring positive pressure (eg, continuous positive airway pressure \[CPAP\], bilevel positive airway pressure \[BiPAP\], intubation and mechanical ventilation); Grade 5: death. |
| Number of Participants With Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) Graded According to American Society for Transplantation and Cellular Therapy (ASTCT) Criteria | From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 20.14 months) | ICANS Grade 1: immune effector cell encephalopathy (ICE) score 7-9, participant awakens spontaneously; Grade 2: ICE score 3-6, participant awakens to voice; Grade 3: ICE score 0-2, participant awakens only to tactile stimulus, any clinical seizure focal or generalized that resolved rapidly or nonconvulsive seizures on electroencephalography that resolve with intervention or focal/local edema on neuroimaging; Grade 4: ICE score 0 (participant is unarousable and unable to perform ICE), participant unarousable or requires vigorous or repetitive tactile stimuli to arouse, life-threatening prolonged seizure (\>5 min), repetitive clinical or electrical seizures without return to baseline in between, deep focal motor weakness, diffuse cerebral edema on neuroimaging; decerebrate/decorticate posturing; cranial nerve VI palsy; papilledema, Cushing's triad; Grade 5: death. ICE: measures alterations in speech, orientation, handwriting, attention and receptive aphasia. |
| Serum Concentration of Elranatamab | Pre-dose on Day 1 of Cycle 4 and Pre-dose on Day 1 of Cycle 7 | Total and free concentrations of Elranatamab on Cycle 4 Day 1 (C4D1) and Cycle 7 Day 1 (C7D1) were reported in this outcome measure. |
| Percentage of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) Against Elranatamab | From the date of first dose up to 20.14 months | — |
| Progression Free Survival (PFS) as Per IMWG Criteria by Investigator Assessment | From date of first dose until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months) | PFS was defined as the time from the date of first dose until 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. |
Countries
Australia, Belgium, Canada, France, Germany, Japan, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants with relapsed/refractory multiple myeloma (RRMM), who were refractory to at least 1 proteasome inhibitor, 1 immunomodulatory drug, and 1 anti-cluster of differentiation38 (CD38) monoclonal antibody were included. Study enrolled participants into 2 independent and parallel cohorts: cohort A and B.
Pre-assignment details
A total of 187 participants were enrolled and assigned to study treatment. Results are reported at primary completion date. Data for only those primary and secondary outcome measures whose analysis is complete and final have been reported. Data for remaining secondary outcome measures will be posted upon completion of analysis at secondary completion date.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A BCMA-naïve participants received subcutaneous elranatamab with a priming regimen of 12 milligrams (mg) on Cycle 1 Day 1 and 32 mg on Cycle 1 Day 4 followed by 76 mg weekly thereafter starting from Cycle 1 Day 8. | 123 |
| Cohort B BCMA-exposed participants received subcutaneous elranatamab with a priming regimen of 12 milligrams (mg) on Cycle 1 Day 1 and 32 mg on Cycle 1 Day 4 followed by 76 mg weekly thereafter starting from Cycle 1 Day 8. | 64 |
| Total | 187 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 41 | 26 |
| Overall Study | Ongoing in the study | 75 | 31 |
| Overall Study | Withdrawal by Subject | 7 | 7 |
Baseline characteristics
| Characteristic | Cohort B | Total | Cohort A |
|---|---|---|---|
| Age, Continuous | 65.7 Years STANDARD_DEVIATION 9.42 | 66.6 Years STANDARD_DEVIATION 9.43 | 67.1 Years STANDARD_DEVIATION 9.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 18 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 119 Participants | 85 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 23 Participants | 50 Participants | 27 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 17 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 11 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 17 Participants | 43 Participants | 26 Participants |
| Race (NIH/OMB) White | 44 Participants | 116 Participants | 72 Participants |
| Sex: Female, Male Female | 34 Participants | 89 Participants | 55 Participants |
| Sex: Female, Male Male | 30 Participants | 98 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 43 / 123 | 30 / 64 |
| other Total, other adverse events | 123 / 123 | 63 / 64 |
| serious Total, serious adverse events | 84 / 123 | 44 / 64 |
Outcome results
Primary
Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) as Per International Myeloma Working Group (IMWG) Criteria
ORR: % of participants with best overall response of confirmed stringent complete response (sCR), CR, very good partial response (VGPR) or PR per IMWG criteria. sCR: CR & normal serum free light chain (sFLC) ratio & absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytoma & \<5% plasma cells in BMA, if disease measurable 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 M-protein & 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 were 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 (up to approximately 16 months)
Population: Safety analysis set in each cohort included all enrolled participants in the respective cohort who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A | Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) as Per International Myeloma Working Group (IMWG) Criteria | 61.0 Percentage of participants |
| Cohort B | Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) as Per International Myeloma Working Group (IMWG) Criteria | 34.4 Percentage of participants |
Comparison: Null hypothesis of ORR by BICR for cohort A was 30%.p-value: <0.0001Exact binominal
Comparison: Null hypothesis of ORR by BICR for cohort B was 15%.p-value: <0.0001Exact binominal
Secondary
Cohort A Only: Objective Response Rate as Per IMWG Criteria by BICR for Participants With Extramedullary Disease (EMD) at Baseline
ORR: % of participants with best overall response of confirmed stringent complete response (sCR), CR, very good partial response (VGPR) or PR per IMWG criteria. sCR: CR & normal serum free light chain (sFLC) ratio & absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytoma & \<5% plasma cells in BMA, if disease measurable 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 M-protein & 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 were 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 (up to approximately 16 months)
Population: Safety analysis set included all enrolled participants who received at least one dose of study intervention. Here, 'Overall Number of Participants Analyzed' signifies number of participants with EMD at baseline. This outcome measure was planned only in Cohort A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A | Cohort A Only: Objective Response Rate as Per IMWG Criteria by BICR for Participants With Extramedullary Disease (EMD) at Baseline | 38.5 Percentage of participants |
Comparison: Null hypothesis of ORR by BICR for cohort A was 12%.p-value: <0.0001Exact binominal
Secondary
Cohort A Only: Objective Response Rate as Per IMWG Criteria by BICR for Participants Without EMD at Baseline
ORR: % of participants with best overall response of confirmed stringent complete response (sCR), CR, very good partial response (VGPR) or PR per IMWG criteria. sCR: CR & normal serum free light chain (sFLC) ratio & absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytoma & \<5% plasma cells in BMA, if disease measurable 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 M-protein & 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 were 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 (up to approximately 16 months)
Population: Safety analysis set included all enrolled participants who received at least one dose of study intervention. Here, 'Overall Number of Participants Analyzed' signifies number of participants without EMD at baseline. This outcome measure was planned only in Cohort A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A | Cohort A Only: Objective Response Rate as Per IMWG Criteria by BICR for Participants Without EMD at Baseline | 71.4 Percentage of participants |
Comparison: Null hypothesis of ORR by BICR for cohort A was 38%.p-value: <0.0001Exact binominal
Secondary
Complete Response Rate as Per IMWG Criteria by Investigator Assessment
CRR: % of participants with BOR of confirmed sCR/CR per IMWG criteria. sCR: CR & normal serum free light chain (sFLC) ratio & absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytoma & \<5% plasma cells in BMA, if disease measurable by sFLC only, preceding criteria plus normal sFLC ratio.
Time frame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 20.14 months)
Secondary
Complete Response Rate (CRR) as Per IMWG Criteria by BICR
CRR: % of participants with BOR of confirmed sCR/CR per IMWG criteria. sCR: CR & normal serum free light chain (sFLC) ratio & absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytoma & \<5% plasma cells in BMA, if disease measurable by sFLC only, preceding criteria plus normal sFLC ratio.
Time frame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 20.14 months)
Secondary
Duration of Complete Response (DOCR) as Per IMWG Criteria by BICR
DOCR: time from first documentation of sCR/CR 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 sCR/CR subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months)
Secondary
Duration of Complete Response (DOCR) as Per IMWG Criteria by Investigator Assessment
DOCR: time from first documentation of sCR/CR 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 sCR/CR subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months)
Secondary
Duration of Response as Per IMWG Criteria by Investigator Assessment
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 occurred first, or censoring (up to approximately 20.14 months)
Secondary
Duration of Response (DOR) as Per IMWG Criteria by BICR
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 occurred first, or censoring (up to approximately 20.14 months)
Secondary
Minimal Residual Disease (MRD) Negativity Rate Per IMWG Sequencing Criteria
MRD negativity rate was the percentage of participants with CR/sCR and with negative MRD per IMWG sequencing criteria.
Time frame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 20.14 months)
Secondary
Number of Participants With Cytokine Release Syndrome (CRS) Graded According to American Society for Transplantation and Cellular Therapy (ASTCT) Criteria
CRS Grade 1: temperature \>=38°C without hypotension or hypoxia; Grade 2: temperature \>=38°C with hypotension not requiring vasopressors, and/or hypoxia requiring low-flow nasal cannula, facemask or blow-by; Grade 3: temperature \>=38°C with hypotension requiring a vasopressor with or without vasopressin and/or hypoxia requiring high-flow nasal cannula, facemask, nonrebreather mask, or Venturi mask; Grade 4: temperature \>=38°C with hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring positive pressure (eg, continuous positive airway pressure \[CPAP\], bilevel positive airway pressure \[BiPAP\], intubation and mechanical ventilation); Grade 5: death.
Time frame: From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 20.14 months)
Secondary
Number of Participants With Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) Graded According to American Society for Transplantation and Cellular Therapy (ASTCT) Criteria
ICANS Grade 1: immune effector cell encephalopathy (ICE) score 7-9, participant awakens spontaneously; Grade 2: ICE score 3-6, participant awakens to voice; Grade 3: ICE score 0-2, participant awakens only to tactile stimulus, any clinical seizure focal or generalized that resolved rapidly or nonconvulsive seizures on electroencephalography that resolve with intervention or focal/local edema on neuroimaging; Grade 4: ICE score 0 (participant is unarousable and unable to perform ICE), participant unarousable or requires vigorous or repetitive tactile stimuli to arouse, life-threatening prolonged seizure (\>5 min), repetitive clinical or electrical seizures without return to baseline in between, deep focal motor weakness, diffuse cerebral edema on neuroimaging; decerebrate/decorticate posturing; cranial nerve VI palsy; papilledema, Cushing's triad; Grade 5: death. ICE: measures alterations in speech, orientation, handwriting, attention and receptive aphasia.
Time frame: From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 20.14 months)
Secondary
Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Laboratory Parameters by NCI CTCAE v 5.0
CTCAE version 5.0 Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Time frame: From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 20.14 months)
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAE) Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered treatment-emergent relative to study intervention if the adverse event start date was during the on-treatment period (i.e. the time from the first dose of study intervention through the minimum of 90 days after last dose, or \[start day of new anticancer therapy - 1 day\]). CTCAE version 5.0 Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening; Grade 5: death.
Time frame: From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 20.14 months)
Secondary
Objective Response Rate as Per IMWG Criteria by Investigator Assessment
ORR: % of participants with best overall response of confirmed stringent complete response (sCR), CR, very good partial response (VGPR) or PR per IMWG criteria. sCR: CR & normal serum free light chain (sFLC) ratio & absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytoma & \<5% plasma cells in BMA, if disease measurable 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 M-protein & 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 were 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 (up to approximately 20.14 months)
Secondary
Overall Survival (OS)
Overall survival (OS) was defined as the time from the date of first dose until death due to any cause.
Time frame: From the date of first dose until death due to any cause. Participants not known to have died were censored on the date of last known alive (up to approximately 20.14 months)
Secondary
Percentage of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) Against Elranatamab
Time frame: From the date of first dose up to 20.14 months
Secondary
Progression Free Survival (PFS) as Per IMWG Criteria by BICR
PFS was defined as the time from the date of first dose until 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 date of first dose until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months)
Secondary
Progression Free Survival (PFS) as Per IMWG Criteria by Investigator Assessment
PFS was defined as the time from the date of first dose until 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 date of first dose until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 20.14 months)
Secondary
Serum Concentration of Elranatamab
Total and free concentrations of Elranatamab on Cycle 4 Day 1 (C4D1) and Cycle 7 Day 1 (C7D1) were reported in this outcome measure.
Time frame: Pre-dose on Day 1 of Cycle 4 and Pre-dose on Day 1 of Cycle 7
Population: The pharmacokinetic (PK) analysis set was a subset of safety analysis set and included participants who had at least one post dose concentration measurement. Here, Overall Number of Participants Analyzed signifies maximum participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A | Serum Concentration of Elranatamab | Total elranatamab concentrations (C4D1) | 31100 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49 |
| Cohort A | Serum Concentration of Elranatamab | Total elranatamab concentrations (C7D1) | 37960 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
| Cohort A | Serum Concentration of Elranatamab | Free elranatamab concentrations (C4D1) | 19090 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 89 |
| Cohort A | Serum Concentration of Elranatamab | Free elranatamab concentrations (C7D1) | 32830 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 81 |
| Cohort B | Serum Concentration of Elranatamab | Free elranatamab concentrations (C7D1) | 29880 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49 |
| Cohort B | Serum Concentration of Elranatamab | Total elranatamab concentrations (C4D1) | 22840 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 63 |
| Cohort B | Serum Concentration of Elranatamab | Free elranatamab concentrations (C4D1) | 16170 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 114 |
| Cohort B | Serum Concentration of Elranatamab | Total elranatamab concentrations (C7D1) | 29880 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 77 |
Secondary
Time-to-Response (TTR) as Per IMWG Criteria by BICR
TTR was defined, for participants with an objective response per IMWG criteria, as the time from the date of first dose to the first documentation of objective response that was subsequently confirmed.
Time frame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 16 months)
Population: Safety analysis set in each cohort included all enrolled participants in the respective cohort who received at least one dose of study intervention. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A | Time-to-Response (TTR) as Per IMWG Criteria by BICR | 1.22 Months |
| Cohort B | Time-to-Response (TTR) as Per IMWG Criteria by BICR | 1.92 Months |
Secondary
Time-to-Response (TTR) as Per IMWG Criteria by Investigator Assessment
TTR was defined, for participants with an objective response per IMWG criteria, as the time from the date of first dose to the first documentation of objective response that was subsequently confirmed.
Time frame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 20.14 months)