BCMA, BCMA-CD3 Bispecific, Bispecific, Bispecific Antibody, Elranatamab, MagnetisMM-8, Multiple Myeloma, Myeloma, PF-06863135, Refractory Multiple Myeloma, Relapsed Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Neoplasms, Plasma Cell, Neoplasms by Histologic Type, Neoplasms, Hemostatic Disorders, Vascular Diseases, Cardiovascular Diseases, Paraproteinemias, Blood Protein Disorders, Hematologic Diseases, Hemorrhagic Disorders, Lymphoproliferative Disorders, Immunoproliferative Disorders, Immune System Diseases
Brief summary
The purpose of this study is to understand the study medicine (called Elranatamab, or PF-06863135) as potential treatment for refractory multiple myeloma. Multiple myeloma is a form of cancer in the bone that forces healthy blood cells to go out. Sometimes, multiple myeloma does not respond to current therapy or quickly progresses, and this is called refractory multiple myeloma. Elranatamab is a study medicine that target multiple myeloma and activates the human body to fight against this disease. We are seeking Chinese participants to take part in this study. The study will be 2 parts, called part 1b and part 2. In part 1b, participants will receive Elranatamab at 2 steps priming and full dose as a sc (subcutaneous injection) therapy. We will monitor participants' safety and reactions to the study medicine. This will help us understand the dosage of Elranatamab to be used safely. In part 2 of the study, participants will receive Elranatamab and their multiple myeloma growth will be monitored. This will help us understand if Elranatamab, when used alone, may be a therapy for refractory multiple myeloma. Participants in this part of the study are expected to take part for about 2 years.
Interventions
DRUGElranatamab
BCMA-CD3 bispecific antibody
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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: * Serum M-protein ≥0.5 g/dL * Urinary M-protein excretion ≥200 mg/24 hours * 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 * ECOG performance status ≤2 * Adequate BM function characterized by the following: 1. Absolute neutrophil count ≥1.0 × 10\^9/L 2. Platelets ≥ 25 × 10\^9/L 3. Hemoglobin ≥8 g/dL * 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 or active GVHD within 12 weeks prior to enrollment. * Previous treatment with an anti-BCMA directed therapy * Impaired cardiovascular function or clinically significant cardiovascular diseases * Ongoing Grade ≥2 peripheral sensory or motor neuropathy. History of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy. * 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 |
|---|---|---|
| Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT) | Cycle 1 (28 days) | Grade(G)4 neutropenia \>5 day; febrile neutropenia (absolute neutrophil count \[ANC\] \<1000/millimeter cube (mm\^3) with single temperature \>38.3 degree Celsius (deg C) or sustained temp\>=38 deg C for \>1 hour(H); G\>=3 neutropenia with infection; G4 thrombocytopenia (unless baseline count \>=25,000/mm\^3 and \<50,000/mm\^3, in which case G4 thrombocytopenia to be accompanied by \>=G2 bleeding); Platelet count \<10,000/mm\^3; G3 thrombocytopenia with \>=G2 bleeding; G\>=4 AE; G3 cytokine release syndrome(CRS) except CRS not maximally treated/improved to \<=G1 within 48H; G3 AE except AE attributed to CRS, G3 nausea,vomiting,diarrhea improved to G\<=2 within 72H after medical management, G3 fatigue \<1 week, G3 AE recovered to baseline/G1 within 5 day; confirmed drug-induced liver injury; G3-4 laboratory (lab) abnormality except G3-4 lab abnormality improved to G\<=2 within 72H after medical management & without sequelae;G3 injection site reaction; G2/other clinically important AE may be considered DLT. |
| 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 (approximately up to 16 months) | ORR: Percentage 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 |
|---|---|---|
| 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 37 months) | CRR: Percentage 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 (CRR) 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 37 months) | CRR: Percentage 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 (ORR) 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 37 months) | ORR: Percentage 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 37 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 the first documentation of sCR/CR, until confirmed PD per IMWG criteria, or death due to any cause, whichever occurred first (up to approximately 37 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 37 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. |
| 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 37 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. |
| 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 37 months) | OS was defined as time from 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 occurs first (approximately up to 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 occurs first (up to approximately 37 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. |
| 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 37 months) | MRD negativity rate was the percentage of participants with CR/sCR and with negative MRD per IMWG sequencing criteria. |
| 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 37 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. |
| 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 37 months) | ASTCT CRS Grading: 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 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 37 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. |
| Maximum Serum Concentration (Cmax) of Free Elranatamab | Cycle 1: Pre-dose, 6 hours post-dose on Day 1, 24, 48 hours post-dose, Day 4: pre-dose, 24 hour post-dose, Day 8 pre-dose, 6 hours post-dose, Day 15,22: pre-dose, Cycles 2, 3 ,4,7: pre-dose (1 cycle =28 days) | — |
| Time To Maximum Serum Concentration (Tmax) of Free Elranatamab | Cycle 1: Pre-dose, 6 hours post-dose on Day 1, 24, 48 hours post-dose, Day 4: pre-dose, 24 hour post-dose, Day 8 pre-dose, 6 hours post-dose, Day 15,22: pre-dose, Cycles 2, 3 ,4,7: pre-dose (1 cycle =28 days) | — |
| Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of Free Elranatamab | Cycle 1: Pre-dose, 6 hours post-dose on Day 1, 24, 48 hours post-dose, Day 4: pre-dose, 24 hour post-dose, Day 8 pre-dose, 6 hours post-dose, Day 15,22: pre-dose, Cycles 2, 3 ,4,7: pre-dose (1 cycle =28 days) | — |
| Serum Concentration of Free Elranatamab | Up to 37 months | — |
| Percentage of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) Against Elranatamab | From the date of first dose up to 37 months | — |
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life of Cancer Participants Core Module (EORTC QLQ-C30) | Baseline and up to 37 months | EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale. All the scales and single-item measures range in score from 0 to 100. Higher scores on the functional scales represent higher levels of functioning. Higher scores on the global health status/quality of life scale represent higher health status/quality of life. Higher scores on symptom scales/items represent a greater presence of symptoms. |
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Myeloma-Specific Module (EORTC QLQ-MY20) | Baseline and up to 37 months | EORTC MY20 is a myeloma-specific module developed by the EORTC group specifically to assess quality of life in participants with multiple myeloma. It contains 20 items which can be grouped into a disease symptom subscale (6 items), side effects of treatment subscale (10 items), body image (1 item) and future perspective subscale (3 items). All transformed scale scores range from 0 to 100 with higher scores indicating worse symptoms (Disease Symptoms and Side Effects of Treatment) or better support/functioning (Future Perspective and Body Image). |
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ CIPN20) | Baseline and up to 37 months | EORTC QLQ CIPN20 is a module developed by the EORTC group to assess chemotherapy-induced peripheral neuropathy. It contains 20 items which can be grouped into a sensory subscale (9 items), motor subscale (8 items) and autonomic subscale (3 items). Sensory scale scores range from 1 to 36, motor scale scores range from 1 to 32, and autonomic scale scores range from 1 to 12 for men and 1-8 for women (erect dysfunction item excluded). Higher scores indicate worse neuropathy. |
| Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Index Score and in EQ-5D Visual Analogue Score (VAS) (EQ-VAS) | Baseline and up to 37 months | The EQ-5D is a 6-item questionnaire with 2 components, a Health State Profile which has individuals rate their level of problems in 5 areas (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and a VAS in which patients rate their overall health status from 0 (worst imaginable) to 100 (best imaginable). Overall scores range from 0 to 1, with lower scores representing higher levels of dysfunction. EQ-VAS records the participant's self-rated health on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state). |
| Number of Participants With Treatment Emergent Adverse Events (TEAE), Serious TEAEs, Treatment Related TEAEs, Serious Treatment Related TEAEs as 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 37 months) | AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to study intervention. 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. An AE was considered treatment-emergent if it 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. CTCAE version 5.0 Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening; Grade 5: death. |
| Duration of Response (DOR) 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 37 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. |
Countries
China
Participant flow
Recruitment details
Chinese participants with relapsed/refractory multiple myeloma (RRMM), who were refractory to at least 1 proteasome inhibitor (PI), 1 immunomodulatory drug (IMiD), and 1 anti-cluster of differentiation38 monoclonal antibody (anti-CD38 mAB) were included.
Pre-assignment details
A total of 38 participants were enrolled and assigned to study treatment. 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 study completion date.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1b Participants received SC elranatamab with a priming regimen of 12 mg on C1D1 and 32 mg on C1D4 followed by 76 mg QW thereafter starting from Cycle 1 Day 8. | 8 |
| Phase 2 Participants received SC elranatamab with a priming regimen of 12 mg on C1D1 and 32 mg on C1D4 followed by 76 mg QW thereafter starting from Cycle 1 Day 8. | 30 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 6 | 11 |
| Overall Study | Ongoing | 1 | 11 |
| Overall Study | Withdrawal by Subject | 1 | 8 |
Baseline characteristics
| Characteristic | Phase 2 | Total | Phase 1b |
|---|---|---|---|
| Age, Continuous | 62.3 Years STANDARD_DEVIATION 7.53 | 60.7 Years STANDARD_DEVIATION 9.07 | 54.8 Years STANDARD_DEVIATION 12.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 38 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 30 Participants | 38 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 12 Participants | 16 Participants | 4 Participants |
| Sex: Female, Male Male | 18 Participants | 22 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 8 | 13 / 30 | 19 / 38 |
| other Total, other adverse events | 8 / 8 | 30 / 30 | 38 / 38 |
| serious Total, serious adverse events | 6 / 8 | 23 / 30 | 29 / 38 |
Outcome results
Primary
Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) as Per International Myeloma Working Group (IMWG) Criteria
ORR: Percentage 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 (approximately up to 16 months)
Population: The primary analysis of ORR as planned per protocol included participants who started with the recommended phase 2 dose \[RP2D\] (including the participants from both Phase 1b and Phase 2 parts). Safety analysis set included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b | Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) as Per International Myeloma Working Group (IMWG) Criteria | 37.5 Percentage of participants |
| Phase 2 | Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) as Per International Myeloma Working Group (IMWG) Criteria | 53.3 Percentage of participants |
| Phase 1b + Phase 2 | Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) as Per International Myeloma Working Group (IMWG) Criteria | 50.0 Percentage of participants |
p-value: 0.0076Exact binomial test
Primary
Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT)
Grade(G)4 neutropenia \>5 day; febrile neutropenia (absolute neutrophil count \[ANC\] \<1000/millimeter cube (mm\^3) with single temperature \>38.3 degree Celsius (deg C) or sustained temp\>=38 deg C for \>1 hour(H); G\>=3 neutropenia with infection; G4 thrombocytopenia (unless baseline count \>=25,000/mm\^3 and \<50,000/mm\^3, in which case G4 thrombocytopenia to be accompanied by \>=G2 bleeding); Platelet count \<10,000/mm\^3; G3 thrombocytopenia with \>=G2 bleeding; G\>=4 AE; G3 cytokine release syndrome(CRS) except CRS not maximally treated/improved to \<=G1 within 48H; G3 AE except AE attributed to CRS, G3 nausea,vomiting,diarrhea improved to G\<=2 within 72H after medical management, G3 fatigue \<1 week, G3 AE recovered to baseline/G1 within 5 day; confirmed drug-induced liver injury; G3-4 laboratory (lab) abnormality except G3-4 lab abnormality improved to G\<=2 within 72H after medical management & without sequelae;G3 injection site reaction; G2/other clinically important AE may be considered DLT.
Time frame: Cycle 1 (28 days)
Population: DLT evaluable analysis set included all participants enrolled to Phase 1b part and who had a DLT in the DLT observation period or completed the DLT observation period without DLT. Participants without DLTs and without the minimum required exposure for reasons other than treatment-related toxicity were not evaluable for DLTs and were replaced.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b | Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT) | 1 Participants |
Secondary
Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of Free Elranatamab
Time frame: Cycle 1: Pre-dose, 6 hours post-dose on Day 1, 24, 48 hours post-dose, Day 4: pre-dose, 24 hour post-dose, Day 8 pre-dose, 6 hours post-dose, Day 15,22: pre-dose, Cycles 2, 3 ,4,7: pre-dose (1 cycle =28 days)
Population: PK parameter analysis set included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single dose and/or multiple-dose PK part. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b | Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of Free Elranatamab | 3.482 Microgram*day per milliliter | Geometric Coefficient of Variation 74 |
| Phase 2 | Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of Free Elranatamab | 3.864 Microgram*day per milliliter | Geometric Coefficient of Variation 37 |
| Phase 1b + Phase 2 | Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of Free Elranatamab | 3.653 Microgram*day per milliliter | Geometric Coefficient of Variation 56 |
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life of Cancer Participants Core Module (EORTC QLQ-C30)
EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale. All the scales and single-item measures range in score from 0 to 100. Higher scores on the functional scales represent higher levels of functioning. Higher scores on the global health status/quality of life scale represent higher health status/quality of life. Higher scores on symptom scales/items represent a greater presence of symptoms.
Time frame: Baseline and up to 37 months
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ CIPN20)
EORTC QLQ CIPN20 is a module developed by the EORTC group to assess chemotherapy-induced peripheral neuropathy. It contains 20 items which can be grouped into a sensory subscale (9 items), motor subscale (8 items) and autonomic subscale (3 items). Sensory scale scores range from 1 to 36, motor scale scores range from 1 to 32, and autonomic scale scores range from 1 to 12 for men and 1-8 for women (erect dysfunction item excluded). Higher scores indicate worse neuropathy.
Time frame: Baseline and up to 37 months
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Myeloma-Specific Module (EORTC QLQ-MY20)
EORTC MY20 is a myeloma-specific module developed by the EORTC group specifically to assess quality of life in participants with multiple myeloma. It contains 20 items which can be grouped into a disease symptom subscale (6 items), side effects of treatment subscale (10 items), body image (1 item) and future perspective subscale (3 items). All transformed scale scores range from 0 to 100 with higher scores indicating worse symptoms (Disease Symptoms and Side Effects of Treatment) or better support/functioning (Future Perspective and Body Image).
Time frame: Baseline and up to 37 months
Secondary
Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Index Score and in EQ-5D Visual Analogue Score (VAS) (EQ-VAS)
The EQ-5D is a 6-item questionnaire with 2 components, a Health State Profile which has individuals rate their level of problems in 5 areas (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and a VAS in which patients rate their overall health status from 0 (worst imaginable) to 100 (best imaginable). Overall scores range from 0 to 1, with lower scores representing higher levels of dysfunction. EQ-VAS records the participant's self-rated health on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time frame: Baseline and up to 37 months
Secondary
Complete Response Rate (CRR) as Per IMWG Criteria by BICR
CRR: Percentage 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 37 months)
Secondary
Complete Response Rate (CRR) as Per IMWG Criteria by Investigator Assessment
CRR: Percentage 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 37 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 37 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 the first documentation of sCR/CR, until confirmed PD per IMWG criteria, or death due to any cause, whichever occurred first (up to approximately 37 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 37 months)
Secondary
Duration of Response (DOR) 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 37 months)
Secondary
Maximum Serum Concentration (Cmax) of Free Elranatamab
Time frame: Cycle 1: Pre-dose, 6 hours post-dose on Day 1, 24, 48 hours post-dose, Day 4: pre-dose, 24 hour post-dose, Day 8 pre-dose, 6 hours post-dose, Day 15,22: pre-dose, Cycles 2, 3 ,4,7: pre-dose (1 cycle =28 days)
Population: Pharmacokinetic (PK) parameter analysis set included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single dose and/or multiple-dose PK part. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b | Maximum Serum Concentration (Cmax) of Free Elranatamab | 0.8762 Microgram per milliliter | Geometric Coefficient of Variation 66 |
| Phase 2 | Maximum Serum Concentration (Cmax) of Free Elranatamab | 0.8039 Microgram per milliliter | Geometric Coefficient of Variation 24 |
| Phase 1b + Phase 2 | Maximum Serum Concentration (Cmax) of Free Elranatamab | 0.8420 Microgram per milliliter | Geometric Coefficient of Variation 48 |
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 37 months)
Secondary
Number of Participants With Cytokine Release Syndrome (CRS) Graded According to American Society for Transplantation and Cellular Therapy (ASTCT) Criteria
ASTCT CRS Grading: 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 37 months)
Secondary
Number of Participants With Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Graded According to 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 37 months)
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAE), Serious TEAEs, Treatment Related TEAEs, Serious Treatment Related TEAEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to study intervention. 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. An AE was considered treatment-emergent if it 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. 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 37 months)
Secondary
Objective Response Rate (ORR) as Per IMWG Criteria by Investigator Assessment
ORR: Percentage 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 37 months)
Secondary
Overall Survival (OS)
OS was defined as time from 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 37 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 37 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 37 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 37 months)
Secondary
Serum Concentration of Free Elranatamab
Time frame: Up to 37 months
Secondary
Time To Maximum Serum Concentration (Tmax) of Free Elranatamab
Time frame: Cycle 1: Pre-dose, 6 hours post-dose on Day 1, 24, 48 hours post-dose, Day 4: pre-dose, 24 hour post-dose, Day 8 pre-dose, 6 hours post-dose, Day 15,22: pre-dose, Cycles 2, 3 ,4,7: pre-dose (1 cycle =28 days)
Population: PK parameter analysis set included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single dose and/or multiple-dose PK part. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b | Time To Maximum Serum Concentration (Tmax) of Free Elranatamab | 7.00 Days |
| Phase 2 | Time To Maximum Serum Concentration (Tmax) of Free Elranatamab | 8.00 Days |
| Phase 1b + Phase 2 | Time To Maximum Serum Concentration (Tmax) of Free Elranatamab | 7.00 Days |
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 occurs first (approximately up to 16 months)
Population: Safety analysis set included all enrolled participants who received at least 1 dose of study intervention. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b | Time-to-Response (TTR) as Per IMWG Criteria by BICR | 2.04 Months |
| Phase 2 | Time-to-Response (TTR) as Per IMWG Criteria by BICR | 1.45 Months |
| Phase 1b + Phase 2 | Time-to-Response (TTR) as Per IMWG Criteria by BICR | 1.51 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 occurs first (up to approximately 37 months)