MAGNETISMM-2: Study of Elranatamab (PF-06863135) in Japanese Participants With Multiple Myeloma
- Conditions
- Relapsed or Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT04798586
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this study is to confirm the safety and tolerability of elranatamab (PF-06863135) in Japanese participants with relapsed or refractory MM.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 4
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Diagnosis of multiple myeloma (IMWG criteria)
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Measurable disease, as defined by at least 1 of the following
- Serum myeloma (M) protein ≥0.5 g/dL (5 g/L)
- Urine M protein ≥200 mg/24 h
- Serum free light chain (FLC) >100 mg/L (10 mg/dL) with abnormal kappa:lambda ratio
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Participants must have progressed on or been intolerant of at least 3 prior therapies including proteasome inhibitor, IMID drug and anti-CD38 antibody, either in combination or as a single agent
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ECOG PS 0, 1 or 2. PS 3 is permitted if PS is due solely to bone pain
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Adequate bone marrow, hematological, kidney and liver function
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Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1
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Not pregnant and willing to use contraception
- POEMS syndrome
- Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
- History of active autoimmune disorders
- Any form of primary immunodeficiency
- History of severe immune-mediated adverse event with prior immunomodulatory treatment
- Stem cell transplant within 12 weeks prior to enrollment
- Active graft versus host disease other than Grade 1 skin involvement, or that requiring immunosuppressive treatment
- Requirement for systemic immune suppressive medication
- Active, uncontrolled bacterial, fungal, or viral infection, including HBV, HCV, known HIV or AIDS related illness and SARS-CoV2
- Previous administration with an investigational drug within 4 weeks or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer)
- Known or suspected hypersensitivity to component of elranatamab (PF-06863135), murine and bovine products
- Live attenuated vaccine within 4 weeks
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Elranatamab (PF-06863135) Elranatamab (PF-06863135) BCMA-CD3 bispecific antibody
- Primary Outcome Measures
Name Time Method Number of Participants With Dose Limiting Toxicities (DLTs) Up to 4 weeks DLT was defined as any of the following: Treatment Emergent Adverse Events (AEs) occurring in Cycle 0 and Cycle 1 (total 4 weeks): Grade (G) 4 neutropenia lasting greater than (\>)7 days; febrile neutropenia (absolute neutrophil count \[ANC\] less than (\<)1,000 per millimeter cube (/mm\^3) with single temperature \>38.3 degree Celsius (deg C), or sustained temperature of greater than or equal to (\>=) 38deg C for \>1 hour \[h\]); G\>=3 neutropenia with infection; G4 thrombocytopenia (unless the baseline count was \>=25,000/mm\^3 and \<50,000/mm\^3, in which case G4 thrombocytopenia was to be accompanied by \>=G2 bleeding), Platelet count \<10,000/mm\^3 was considered a DLT irrespective of other factors; G3 thrombocytopenia with \>=G2 bleeding; G4 AEs; G3 AE \>=5 days despite optimal supportive care (except AEs attributed to cytokine release syndrome \[CRS\]); G3 CRS (except CRS that have not been maximally treated or improved to \<=G1 within 48h); confirmed drug induced liver injury.
- Secondary Outcome Measures
Name Time Method Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs From first dose of study intervention and up to 90 days after last dose or start of new anticancer therapy (maximum of 65.1 weeks of treatment) An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. An SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. A TEAE was defined as an AE that first occurred from the first dose of the study intervention until 90 days after the last dose or the day before starting a new anticancer therapy, whichever occurred first. Treatment related AEs and SAEs were defined as AEs and SAEs which was related to the treatment.
Number of Participants With Grade 3 or 4, Grade 5 TEAEs and Treatment Related TEAEs Based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5 Except for CRS and ICANS Graded According to ASTCT Grading Criteria 2019 From first dose of study intervention and up to 90 days after last dose or start of new anticancer therapy (maximum of 65.1 weeks of treatment) CTCAEv5.0 G3:severe/clinically significant;G4:life-threatening;G5:death.ASTCT CRS G3:temp\>=38degC,hypotension required vasopressor with/without vasopressin and/or hypoxia required high-flow nasal cannula,facemask,nonrebreather mask or venturi mask;G4:temp\>=38degC,hypotension required multiple vasopressors(excluding vasopressin)and/or hypoxia required positive pressure;G5:death.ICANS G3:ICE score0-2,awakens only to tactile stimulus,clinical seizure focal/generalized resolves rapidly or nonconvulsive seizures on electroencephalography resolve with intervention,focal/local edema on neuroimaging;G4:ICEscore 0(unarousable unable to perform ICE),unarousable or requires vigorous/repetitive tactile stimuli to arouse,stupor/coma,life-threatening prolonged seizure(\>5 min),repetitive clinical/electrical seizure without return to baseline,deep focal motor weakness,diffuse cerebral edema on neuroimaging,decerebrate/decorticate posturing,cranial nerve VI palsy,papilledema,Cushing's triad;G5:death.
Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Hematology Parameters by NCI CTCAE v 5.0 From first dose of study intervention and up to 90 days after last dose or start of new anticancer therapy (maximum of 65.1 weeks of treatment) Hematology parameters that were assessed included: Anemia, Lymphocyte count decreased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased. Abnormalities were graded based on National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 - Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Number of Participants With Shift From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post -Baseline in Chemistry Parameters by NCI CTCAE v 5.0 From first dose of study intervention and up to 90 days after last dose or start of new anticancer therapy (maximum of 65.1 weeks of treatment) Chemistry parameters that were assessed included: Alanine aminotransferase increased, Alkaline phosphatase increased, Aspartate aminotransferase increased, Blood bilirubin increased, Creatinine increased, Hypercalcemia, Hyperkalemia, Hypermagnesemia, Hypernatremia, Hypoalbuminemia, Hypocalcemia, Hypoglycemia, Hypokalemia, Hypomagnesemia, Hyponatremia. Abnormalities were graded based on CTCAE version 5.0- Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Maximum Observed Serum Concentration (Cmax) of Elranatamab Cycle 0: from Cycle 0 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days]; Cycle 1: from Cycle 1 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days] Time to Maximum Concentration (Tmax) of Elranatamab Cycle 0: from Cycle 0 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days]; Cycle 1: from Cycle 1 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days] Area Under the Concentration-time Profile From Time Zero to the Time Tau (AUCtau) of Elranatamab Cycle 0: from Cycle 0 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days]; Cycle 1: from Cycle 1 Day 1 (pre dose to the next dose of study intervention) [maximum of 9 days] Area under the concentration-time profile from time zero to the time tau where the dosing interval (tau = 1 week). AUCtau was determined using the linear/log trapezoidal method.
Pre-dose Trough Serum Concentrations After Multiple Doses of Elranatamab At pre-dose on Day 1 of Cycle 0, 3, 4, 5, 6, 7, 8, 12, 16; at pre-dose on Days 1, 8, 15 of Cycle 1 and 2 Number of Participants With Anti-drug Antibodies (ADA) of Elranatamab From the date of first dose up to maximum of 65.1 weeks of treatment 'A participant was considered ADA positive if baseline titer was missing or negative and participant had \>=1 post-treatment positive titer, or positive titer at baseline and had a \>=4-fold increase in titer from baseline in \>=1 post-treatment sample.
Titers of ADA Cycle1 Day1, Cycle1 Day15, Cycle2 Day1, Cycle3 Day1, Cycle4 Day1, Cycle6 Day1, Cycle8 Day1, Cycle12 Day1, Cycle16 Day1, End of treatment (maximum of 65.1 weeks of treatment) Titers of ADA at specified timepoints were reported in this outcome measure.
Number of Participants With Neutralizing Antibodies (NAb) From the date of first dose up to maximum of 65.1 weeks of treatment A participant was considered NAb positive if baseline titer was missing or negative and participant had \>=1 post-treatment positive titer, or positive titer at baseline and had a \>=4-fold increase in titer from baseline in \>=1 post-treatment sample.
Objective Response Rate (ORR): Percentage of Participants With Objective Response From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (maximum of 65.1 weeks of treatment) ORR:% of participants with best overall response; confirmed stringent complete response(sCR),CR, very good partial response(VGPR) or PR per International Myeloma Working Group criteria.sCR: CR\& normal serum free light chain(sFLC)ratio \&absence of clonal cells in BMB/BMA by immunohistochemistry, immunofluorescence or flow cytometry.CR: negative immunofixation on serum \&urine, disappearance of soft tissue plasmacytoma \&\<5% plasma cells in BMA, if disease measured by sFLC only,preceding criteria plus normal sFLC ratio.VGPR:Serum \& urine M-protein detectable by immunofixation but not on electrophoresis; or \>=90% reduction in serum\&urine M-protein level \<100mg/24h.PR:\>=50% reduction in serum M-protein \& reduction in 24h urinary M-protein by \>=90% or \<200 mg/24h. If serum \& urine M-protein unmeasurable,VGPR \& PR: \>=90% \&\>=50% decrease in difference respectively between involved \& uninvolved sFLC levels \& if present at baseline,\>=90% \& \>=50% reduction in soft tissue plasmacytomas' size.
Time to Response (TTR) From date of first dose to the first documentation of objective response that is subsequently confirmed (maximum of 65.1 weeks of treatment) TTR was defined for participants with confirmed objective response (sCR,CR,VGPR and PR) as the time from first date of study intervention to the date of first documentation of objective response. sCR: CR and normal sFLC ratio with absence of clonal cells in BMB/BMA by immunohistochemistry, immunofluorescence or flow cytometry.CR: negative immunofixation on serum and urine,disappearance of soft tissue plasmacytoma, \<5% plasma cells in BMA, if disease measured by sFLC only,preceding criteria plus normal sFLC ratio.VGPR:Serum and urine M-protein detectable by immunofixation but not on electrophoresis; or \>=90% reduction in serum and urine M-protein level \<100mg/24h.PR:\>=50% reduction in serum M-protein and reduction in 24h urinary M-protein by \>=90% or \<200 mg/24h.If serum and urine M-protein unmeasurable,VGPR \& PR: \>=90%,\>=50% decrease in difference respectively between involved and uninvolved sFLC levels,if present at baseline,\>=90%, \>=50% reduction in soft tissue plasmacytomas' size.
Duration of Response (DOR) From first documentation of objective response subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurs first, or censoring date (maximum of 65.1 weeks of treatment) DOR: time from first documentation of objective response subsequently confirmed, until first documentation of confirmed PD or death due to any cause, whichever occurred first. PD= increase of \>=25% from lowest value in \>=1 of following (serum M-protein \[absolute increase \>=0.5g/dL\]; serum M-protein increase \>=1g/dL \[when lowest M-protein \>=5g/dL\]; urine M-protein \[absolute increase \>=200mg/24h\]; participants without measurable serum \& urine M-protein levels, difference between involved \& uninvolved sFLC levels \[absolute increase \>10mg/dL\]; in participants without measurable serum, urine M-protein levels \& involved sFLC levels: bone marrow plasma-cell % irrespective of baseline status \[absolute increase \>=10%\]; appearance of new lesion,\>=50% increase from nadir in SPD of \>1 lesion, or \>=50% increase in longest diameter of previous lesion \>1cm in short axis; \>=50% increase in circulating plasma cells \[\>=200cells/μL\] if this is the only measure of disease.
Progression Free Survival (PFS) From date of first dose until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurs first, or censoring date (maximum of 65.1 weeks of treatment) Progression free survival (PFS) was the time from the first date of the study intervention to the date of the first documentation of confirmed progression, or death due to any cause.
Overall Survival (OS) From the date of first dose until death due to any cause or censoring date (maximum of 65.1 weeks of treatment) Overall survival (OS) was the time from the first date of the study intervention to the date of death due to any cause. Participants not known to have died are censored on the date of last known alive.
Minimal Residual Disease (MRD) Negativity Rate From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (maximum of 65.1 weeks of treatment) MRD negativity rate was defined as percentage of participants with CR or sCR with negative MRD per IMWG sequencing criteria by bone marrow aspirate (BMA). sCR: CR and normal sFLC ratio with absence of clonal cells in BMB/BMA by immunohistochemistry, immunofluorescence or flow cytometry.CR: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytoma and \<5% plasma cells in BMA, if disease measured by sFLC only, preceding criteria plus normal sFLC ratio. MRD was reported at threshold frequency of 10\^5 and 10\^6.
Trial Locations
- Locations (2)
Japanese Red Cross Medical Center
🇯🇵Shibuya-ku, Tokyo, Japan
Nagoya City University Hospital
🇯🇵Nagoya, Aichi, Japan