MagnetisMM-4: Umbrella Study of Elranatamab (PF-06863135) in Combination With Anti-Cancer Treatments in Multiple Myeloma

A PHASE 1B/2, OPEN LABEL UMBRELLA STUDY OF ELRANATAMAB (PF-06863135), A B-CELL MATURATION ANTIGEN (BCMA) CD3 BISPECIFIC ANTIBODY, IN COMBINATION WITH OTHER ANTI-CANCER TREATMENTS IN PARTICIPANTS WITH MULTIPLE MYELOMA

The purpose of this study is to determine the Recommended Phase 2 Dose and clinical benefit of elranatamab in combination with other anti-cancer therapies in participants with multiple myeloma.

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Elranatamab + Nirogacestat; Drug: Elranatamab + lenalidomide + dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Arthur J.E. Child Comprehensive Cancer Centre
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital - General Campus
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Gilbert, Arizona, United States, 85234
      • Banner Gateway Medical Center
    • Gilbert, Arizona, United States, 85234
      • Banner Gateway Medical Pavilion
    • Phoenix, Arizona, United States, 85012
      • Banner Health d.b.a. Banner MD Anderson Cancer Center
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
    • Encino, California, United States, 91316
      • Clinical Research Advisors
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute (SOCCI)
    • Los Angeles, California, United States, 90020
      • Clinical Research Advisors
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center Oncology IDS Pharmacy Attn:Suwicha Limvorasak ,PharmaD
    • Los Angeles, California, United States, 90048
      • Clinical Research Advisors
    • Tarzana, California, United States, 91356
      • Cedars-Sinai Tarzana
  • Florida
    • Coral Gables, Florida, United States, 33146
      • University of Miami
    • Coral Gables, Florida, United States, 33146
      • Sylvester Comprehensive Cancer Center - The Lennar Foundation Medical Center
    • Deerfield Beach, Florida, United States, 33442
      • Sylvester Comprehensive Cancer Center- Deerfield Beach
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center
    • Miami, Florida, United States, 33136
      • UHealth Tower
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • The Johns Hopkins University School of Medicine
    • Baltimore, Maryland, United States, 21231
      • OIDS, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Baltimore, Maryland, United States, 21231
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Also Imaging Facility)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Relapsed/refractory multiple myeloma with at least 3 prior lines of therapy
• Refractory to at least one IMiD, one proteasome inhibitor, and one anti-CD38 antibody

• Measurable disease defined by at least one 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
• ECOG performance status 0 -1
• Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade </= 1

Exclusion Criteria:

• Active plasma cell leukemia
• Amyloidosis
• Stem cell transplant with 12 weeks prior to enrollment, or active GVHD
• POEMS syndrome
• Any active uncontrolled bacterial, fungal, or viral infection
• Impaired cardiovascular function or clinically significant cardiovascular diseases within 6 months prior to enrollment
• Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of study treatment (whichever is longer)
• Sub-Study A Only: Previous treatment with BCMA bispecific antibody
• Sub-Study B Only: Previous treatment with BCMA directed therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sub-Study A; BCMA-CD3 bispecific antibody + gamma secretase inhibitor	Drug: Elranatamab + Nirogacestat; BCMA-CD3 bispecific antibody + gamma secretase inhibitor; Other Names: PF-06863135, Ogsiveo
Experimental: Sub-Study B; BCMA-CD3 bispecific antibody + immunomodulatory drug	Drug: Elranatamab + lenalidomide + dexamethasone; BCMA-CD3 bispecific antibody + immunomodulatory; Other Names: PF-06863135; Revlimid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SSA: Number of Participants With Dose Limiting Toxicities (DLTs)- Phase 1b Dose Escalation	DLT- Hematological:Grade (G)4 neutropenia >5 days; febrile neutropenia; G>=3 neutropenia, infection; G4 thrombocytopenia; G3 thrombocytopenia and G>=2 bleeding. Non-hematological: G>=4 adverse events(AEs); G3 cytokine release syndrome(CRS) [except CRS not been maximally treated or improved to G<=1 in 48 hours]; G3 AEs (except AEs attributed to CRS, G3 nausea, vomiting, diarrhea that improve to G2<=72 hours after maximal medical management has been initiated, G3 fatigue < 1 week); confirmed drug-induced liver injury meeting Hy's law criteria; G3-4 laboratory abnormalities(except not associated with clinical sequelae and improve to G=<2 in 72 hours); G2 clinically important/persistent AEs(cause significant dose delay/reduction) may be DLT; G3 injection site reaction, allergic reaction, anaphylaxis. Common Terminology Criteria for Adverse Events(CTCAE) version 5.0: G1:mild AE, G2:moderate, G3:severe, G4:life-threatening consequences; urgent intervention indicated, G5:death related to AE.	From Cycle 0 Day 1 through Cycle 1 Day 28 (approximately up to 35 days)
SSB: Number of Participants With DLTs- Phase 1b	Hematological: G4 neutropenia >5 days; febrile neutropenia; G>=3 neutropenia with infection; G4 thrombocytopenia; G3 thrombocytopenia with G>=2 bleeding. Non-hematological: G>=4 AEs; G3 CRS (except CRS events: not been maximally treated or improved to grade <=1 within 48 hours); G3 AEs (except: AEs attributed to CRS, G3 nausea, vomiting and diarrhea that improve to G2<=72 hours after maximal medical management has been initiated, G3 fatigue < 1 week); confirmed drug-induced liver injury meeting Hy's law criteria; G 3-4 laboratory abnormalities (except: not associated with clinical sequelae and improve to G=<2 within 72 hours); Other clinically important/persistent AEs (that cause significant dose delay/reduction) may be DLT; G3 injection site reaction. CTCAE version 5.0: G1: Mild AE, G2: Moderate, G3: Severe, G4: Life-threatening consequences; urgent intervention indicated, G5: Death related to AE.	From Cycle 0 Day 1 through Cycle 1 Day 28 (approximately up to 42 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SSA: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs- Phase 1b	An adverse event 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, including both serious and all non-serious adverse events. A serious adverse event (SAE): any untoward medical occurrence that, at any dose resulting 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. Relatedness of any AE to treatment to be judged by investigator.	From treatment initiation till study completion
SSA: Number of Participants With Severity of AEs According to Cytokine Release Syndrome (CRS) Graded According to American Society for Transplantation and Cellular Therapy (ASTCT) Grading Criteria 2019- Phase 1b	CRS: supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T-cells and/or other immune effector cells. Symptoms must include fever at the onset, and may include hypotension, hypoxia and end organ dysfunction. As per ASTCT criteria, G1: fever (temperature >=38 degree Celsius), hypotension and/or hypoxia none; G2: fever, hypotension not requiring vasopressors, hypoxia requiring low-flow nasal cannula/facemask or blow-by; G3: fever, hypotension requiring a vasopressor with or without vasopressin, hypoxia requiring high-flow nasal cannula/facemask, nonrebreather mask, or Venturi mask; G4: fever, hypotension requiring multiple vasopressors (excluding vasopressin), hypoxia requiring positive pressure. Organ toxicities associated with CRS graded according to CTCAE v5.0. G1: mild, G2: moderate, G3: severe, G4: life-threatening consequences; urgent intervention indicated. G5: death related to AE.	From treatment initiation till study completion
SSA: Number of Participants With Severity of AEs According to Immune Effector Cell-associated Neurotoxicity Syndrome ICANS Graded According to ASTCT Grading Criteria 2019- Phase 1b	ASTCT for ICANS [immune effector cell-associated encephalopathy (ICE, overall score range 0-10, higher score = better condition). G1: ICE score 7-9, awakens spontaneously; G2: ICE score 3-6, awakens to voice; G3: ICE score 0-2, awakens only to tactile stimulus, any clinical seizure that resolves rapidly or non-convulsive seizures on electroencephalography that resolve with intervention, focal/local oedema on neuroimaging; G4: ICE score 0 (unarousable and unable to perform ICE), unarousable or requires vigorous or repetitive tactile stimuli to arouse. Stupor or coma, life-threatening prolonged seizure (>5 min); or repetitive clinical or electrical seizures without return to baseline in between, deep focal motor weakness such as hemiparesis or paraparesis, diffuse cerebral oedema on neuroimaging; decerebrate or decorticate posturing; or cranial nerve VI (abducens nerve) palsy; or papilledema; or Cushing's triad; G5: death.	From treatment initiation till study completion
SSA: Number of Participants With Laboratory Abnormalities- Phase 1b	Number of participants with laboratory abnormalities will be reported in this outcome measure.	From treatment initiation till study completion
SSA: Objective Response Rate (ORR) as Per International Myeloma Working Group (IMWG) Criteria as Determined by Investigator- Phase 1b	ORR: % of participants with objective response. Stringent complete response(sCR): CR & normal serum free light chain (sFLC) ratio &absence of clonal cells in BMB/BMA by immunohistochemistry or immunofluorescence. CR: negative immunofixation on serum &urine, disappearance of soft tissue plasmacytomas &<5% plasma cells in BMA. If disease measurable by sFLC only, preceding criteria &normal sFLC ratio. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis; or >=90% reduction in serum M-protein & urine M-protein level <100 mg/24h; PR: >=50% reduction of serum M-protein & reduction in 24h urinary M-protein by >=90% or to <200 mg/24 hours (If disease measurable by sFLC only: VGPR & PR: >=90% &>=50% decrease in difference respectively between involved & uninvolved sFLC levels). In addition, if present at baseline, VGPR & PR: >=90% &>=50% reduction compared with baseline in soft tissue plasmacytomas' size.	From treatment initiation till study completion
SSA: Complete Response Rate (CRR) as Per IMWG Criteria as Determined by Investigator- Phase 1b	CRR was defined as the percentage of participants with a Best Overall Response (BOR) of confirmed sCR/CR per IMWG response criteria as determined by investigator. sCR: i) CR; ii) normal serum FLC ratio and absence of clonal cells in BMB/BMA by immunohistochemistry or immunofluorescence (κ/λ ratio <=4:1 or >=1:2 for κ and λ participants, respectively, after counting >=100 plasma cells; iii) if the only measurable disease was by serum FLC levels, sCR was defined as normal serum FLC ratio of 0.26 to 1.65 plus absence of clonal cells in BMB/BMA b by immunohistochemistry or immunofluorescence (κ/λ ratio <=4:1 or >=1:2 for κ and λ participants, respectively, after counting >=100 plasma cells). CR: i) negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in BMA; ii) if the only measurable disease was by serum FLC levels, CR was defined as normal serum FLC ratio of 0.26 to 1.65 plus criteria (i).	From treatment initiation till study completion
SSA: Time to Response (TTR) as Per IMWG Criteria as Determined by Investigator-Phase 1b	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 is subsequently confirmed.	From treatment initiation till study completion
SSA: Duration of Response (DOR) as Per IMWG Criteria as Determined by Investigator- Phase 1b	DOR (for participants (pts) with objective response (OR) per IMWG)=time from the first OR that is confirmed (conf), until conf PD per IMWG, or death due to any cause, whichever occurred first. PD=any of: (i)Increase (inc) >=25% from lowest conf response value of (a)Serum M-component (absolute (abs) inc >=0.5 g/dL) (b)Serum M-protein inc >=1 g/dL if lowest M component >=5 g/dL (c)Urine M-protein (abs inc >=200 mg/24 h) (d)in pts without measurable (meas) serum and urine M-protein levels, difference between involved and uninvolved serum FLC levels (abs inc >10 mg/dL) (e)in pts without meas serum and urine M-protein levels and without meas involved serum FLC, bone marrow plasma-cell (PC) percentage irrespective of baseline status (abs inc >=10%) (ii)appearance of new lesion(s), >=50% inc from nadir in SPD of >1 lesion, or >= 50% inc in longest diameter of a prior lesion >1 cm in short axis (iii)>=50% inc in circulating PC (minimum 200 cells per microliter) if the only measure of disease.	From treatment initiation till study completion
SSA: Duration of Complete Response (DOCR) as Per IMWG Criteria as Determined by Investigator- Phase 1b	DOCR (for participants (pts) with CR/sCR per IMWG)= time from the first CR/sCR that is confirmed (conf), until conf PD per IMWG, or death due to any cause, whichever occurred first. PD=any of: (i)Increase (inc) >=25% from lowest conf response value of (a)Serum M-component (absolute (abs) inc >=0.5 g/dL) (b)Serum M-protein inc >=1 g/dL if lowest M component >=5 g/dL (c)Urine M-protein (abs inc >=200 mg/24 h) (d)in pts without measurable (meas) serum and urine M-protein levels, difference between involved and uninvolved serum FLC levels (abs inc >10 mg/dL) (e)in pts without meas serum and urine M-protein levels and without meas involved serum FLC, bone marrow plasma-cell (PC) percentage irrespective of baseline status (abs inc >=10%) (ii)appearance of new lesion(s), >=50% inc from nadir in SPD of >1 lesion, or >= 50% inc in longest diameter of a prior lesion >1 cm in short axis (iii)>=50% inc in circulating PC (minimum 200 cells per microliter) if the only measure of disease.	From treatment initiation till study completion
SSA: Progression Free Survival (PFS) as Per IMWG Criteria as Determined by Investigator- Phase 1b	PFS=time from date of first dose until confirmed PD per IMWG criteria or death due to any cause, whichever occurred first. PD=any of: (i)Increase (inc) >=25% from lowest confirmed response value of (a)Serum M-component (absolute (abs) inc >=0.5 g/dL) (b)Serum M-protein inc >=1 g/dL if lowest M component >=5 g/dL (c)Urine M-protein (abs inc >=200 mg/24 h) (d)in pts without measurable (meas) serum and urine M-protein levels, difference between involved and uninvolved serum FLC levels (abs inc >10 mg/dL) (e)in pts without meas serum and urine M-protein levels and without meas involved serum FLC, bone marrow plasma-cell (PC) percentage irrespective of baseline status (abs inc >=10%) (ii)appearance of new lesion(s), >=50% inc from nadir in SPD of >1 lesion, or >= 50% inc in longest diameter of a previous lesion >1 cm in short axis (iii)>=50% inc in circulating PC (minimum 200 cells per microliter) if the only measure of disease.	From treatment initiation till study completion
SSA: Overall Survival (OS)- Phase 1b	OS was defined as 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.	From treatment initiation till study completion
SSA: Minimal Residual Disease (MRD) Negativity Rate as Per IMWG Criteria- Phase 1b	MRD negativity rate is defined as the proportion of participants with CR or better by investigator and negative MRD (assessed by central lab) per IMWG sequencing criteria at any time from the date of first dose until the first documentation of confirmed PD, death or start of new anticancer therapy, whichever occurs first. 1) CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in BMA. If the only measurable disease is by serum FLC levels, CR was defined as normal serum FLC ratio of 0.26 to 1.65; 2) Sequencing MRD-negative: Absence of clonal plasma cells by next generation sequencing (NGS) on BMA in which presence of a clone was defined as <2 identical sequencing reads obtained after DNA sequencing of BMA using the LymphoSIGHT platform (or validated equivalent method) with a minimum sensitivity of 1 in 10^5 nucleated cells.	From treatment initiation till study completion
SSA: Pre- and Post-dose Concentrations of Elranatamab- Phase 1b		From treatment initiation till study completion
SSA: Trough Serum Concentrations of Nirogacestat- Phase 1b		From treatment initiation till study completion
SSA: Number of Participants With Anti-drug Antibodies (ADA)- Phase 1b		From treatment initiation till study completion
SSA: Number of Participants With Neutralizing Antibodies (NAb)- Phase 1b		From treatment initiation till study completion
SSB: Number of Participants With TEAEs and Treatment Related TEAEs- Phase 1b	AE: any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention, including both serious and all non-serious adverse events. A SAE: any untoward medical occurrence that, at any dose resulting 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. Relatedness of any AE to treatment to be judged by investigator.	From treatment initiation till study completion
SSB: Number of Participants With Severity of Adverse Events According to CRS Graded According to ASTCT Grading Criteria 2019- Phase 1b Dose Escalation	CRS: supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T-cells and/or other immune effector cells. Symptoms must include fever at the onset, and may include hypotension, hypoxia and end organ dysfunction. As per ASTCT criteria, G1: fever (temperature >=38 degree Celsius), hypotension and/or hypoxia none; G2: fever, hypotension not requiring vasopressors, hypoxia requiring low-flow nasal cannula/facemask or blow-by; G3: fever, hypotension requiring a vasopressor with or without vasopressin, hypoxia requiring high-flow nasal cannula/facemask, nonrebreather mask, or Venturi mask; G4: fever, hypotension requiring multiple vasopressors (excluding vasopressin), hypoxia requiring positive pressure. Organ toxicities associated with CRS graded according to CTCAE v5.0. G1: mild, G2: moderate, G3: severe, G4: life-threatening consequences; urgent intervention indicated. G5: death related to AE.	From treatment initiation till study completion
SSB: Number of Participants With Severity of Adverse Events According to ICANS Graded According to ASTCT Grading Criteria 2019- Phase 1b Dose Escalation	ASTCT for ICANS (ICE, overall score range 0-10, higher score = better condition). G1: ICE score 7-9, awakens spontaneously; G2: ICE score 3-6, awakens to voice; G3: ICE score 0-2, awakens only to tactile stimulus, any clinical seizure that resolves rapidly or non-convulsive seizures on electroencephalography that resolve with intervention, focal/local oedema on neuroimaging; G4: ICE score 0 (unarousable and unable to perform ICE), unarousable or requires vigorous or repetitive tactile stimuli to arouse. Stupor or coma, life-threatening prolonged seizure (>5 min); or repetitive clinical or electrical seizures without return to baseline in between, deep focal motor weakness such as hemiparesis or paraparesis, diffuse cerebral oedema on neuroimaging; decerebrate or decorticate posturing; or cranial nerve VI (abducens nerve) palsy; or papilledema; or Cushing's triad; G5: death.	From treatment initiation till study completion
SSB: Number of Participants With Laboratory Abnormalities- Phase 1b Dose Escalation	Number of participants with laboratory abnormalities will be reported in this outcome measure.	From treatment initiation till study completion
SSB: ORR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation	ORR: % of participants with objective response. sCR: CR & normal sFLC ratio and absence of clonal cells in BMB/BMA by immunohistochemistry or immunofluorescence. CR: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytomas &<5% plasma cells in BMA. If disease measurable by sFLC only, preceding criteria &normal sFLC ratio. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis; or >=90% reduction in serum M-protein & urine M-protein level <100 mg/24h; PR: >=50% reduction of serum M-protein & reduction in 24h urinary M-protein by >=90% or to <200 mg/24 hours (If disease measurable by sFLC only: VGPR & PR: >=90% &>=50% decrease in difference respectively between involved & uninvolved sFLC levels). In addition, if present at baseline, VGPR & PR: >=90% &>=50% reduction compared with baseline in soft tissue plasmacytomas' size.	From treatment initiation till study completion
SSB: CRR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation	CRR was defined as the percentage of participants with a BOR of confirmed sCR/CR per IMWG response criteria as determined by investigator. sCR: i) CR; ii) normal serum FLC ratio and absence of clonal cells in BMB/BMA by immunohistochemistry or immunofluorescence (κ/λ ratio <=4:1 or >=1:2 for κ and λ participants, respectively, after counting >=100 plasma cells; iii) if the only measurable disease was by serum FLC levels, sCR was defined as normal serum FLC ratio of 0.26 to 1.65 plus absence of clonal cells in BMB/BMA b by immunohistochemistry or immunofluorescence (κ/λ ratio <=4:1 or >=1:2 for κ and λ participants, respectively, after counting >=100 plasma cells). CR: i) negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in BMA; ii) if the only measurable disease was by serum FLC levels, CR was defined as normal serum FLC ratio of 0.26 to 1.65 plus criteria (i).	From treatment initiation till study completion
SSB: TTR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation	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 is subsequently confirmed.	From treatment initiation till study completion
SSB: DOR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation	DOR (for participants (pts) with objective response (OR) per IMWG)=time from the first OR that is confirmed (conf), until conf PD per IMWG, or death due to any cause, whichever occurred first. PD=any of: (i)Increase (inc) >=25% from lowest conf response value of (a)Serum M-component (absolute (abs) inc >=0.5 g/dL) (b)Serum M-protein inc >=1 g/dL if lowest M component >=5 g/dL (c)Urine M-protein (abs inc >=200 mg/24 h) (d)in pts without measurable (meas) serum and urine M-protein levels, difference between involved and uninvolved serum FLC levels (abs inc >10 mg/dL) (e)in pts without meas serum and urine M-protein levels and without meas involved serum FLC, bone marrow plasma-cell (PC) percentage irrespective of baseline status (abs inc >=10%) (ii)appearance of new lesion(s), >=50% inc from nadir in SPD of >1 lesion, or >= 50% inc in longest diameter of a prior lesion >1 cm in short axis (iii)>=50% inc in circulating PC (minimum 200 cells per microliter) if the only measure of disease.	From treatment initiation till study completion
SSB: DOCR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation	DOCR (for participants (pts) with CR/sCR per IMWG)= time from the first CR/sCR that is confirmed (conf), until conf PD per IMWG, or death due to any cause, whichever occurred first. PD=any of: (i)Increase (inc) >=25% from lowest conf response value of (a)Serum M-component (absolute (abs) inc >=0.5 g/dL) (b)Serum M-protein inc >=1 g/dL if lowest M component >=5 g/dL (c)Urine M-protein (abs inc >=200 mg/24 h) (d)in pts without measurable (meas) serum and urine M-protein levels, difference between involved and uninvolved serum FLC levels (abs inc >10 mg/dL) (e)in pts without meas serum and urine M-protein levels and without meas involved serum FLC, bone marrow plasma-cell (PC) percentage irrespective of baseline status (abs inc >=10%) (ii)appearance of new lesion(s), >=50% inc from nadir in SPD of >1 lesion, or >= 50% inc in longest diameter of a prior lesion >1 cm in short axis (iii)>=50% inc in circulating PC (minimum 200 cells per microliter) if the only measure of disease.	From treatment initiation till study completion
SSB: PFS as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation	PFS=time from date of first dose until confirmed PD per IMWG criteria or death due to any cause, whichever occurred first. PD=any of: (i)Increase (inc) >=25% from lowest confirmed response value of (a)Serum M-component (absolute (abs) inc >=0.5 g/dL) (b)Serum M-protein inc >=1 g/dL if lowest M component >=5 g/dL (c)Urine M-protein (abs inc >=200 mg/24 h) (d)in pts without measurable (meas) serum and urine M-protein levels, difference between involved and uninvolved serum FLC levels (abs inc >10 mg/dL) (e)in pts without meas serum and urine M-protein levels and without meas involved serum FLC, bone marrow plasma-cell (PC) percentage irrespective of baseline status (abs inc >=10%) (ii)appearance of new lesion(s), >=50% inc from nadir in SPD of >1 lesion, or >= 50% inc in longest diameter of a previous lesion >1 cm in short axis (iii)>=50% inc in circulating PC (minimum 200 cells per microliter) if the only measure of disease.	From treatment initiation till study completion
SSB: OS- Phase 1b Dose Escalation	OS was defined as 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.	From treatment initiation till study completion
SSB: MRD Negativity Rate as Per IMWG Criteria- Phase 1b Dose Escalation	MRD negativity rate is defined as the proportion of participants with CR or better by investigator and negative MRD (assessed by central lab) per IMWG sequencing criteria at any time from the date of first dose until the first documentation of confirmed PD, death or start of new anticancer therapy, whichever occurs first. 1) CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in BMA. If the only measurable disease is by serum FLC levels, CR was defined as normal serum FLC ratio of 0.26 to 1.65; 2) Sequencing MRD-negative: Absence of clonal plasma cells by next generation sequencing (NGS) on BMA in which presence of a clone was defined as <2 identical sequencing reads obtained after DNA sequencing of BMA using the LymphoSIGHT platform (or validated equivalent method) with a minimum sensitivity of 1 in 10^5 nucleated cells.	From treatment initiation till study completion
SSB: Pre- and Post-dose Concentrations of Elranatamab- Phase 1b Dose Escalation		From treatment initiation till study completion
SSB: Trough Serum Concentrations of Lenalidomide- Phase 1b Dose Escalation		From treatment initiation till study completion
SSA: Number of Participants With ADA- Phase 1b Dose Escalation		From treatment initiation till study completion
SSB: Number of Participants With NAb- Phase 1b Dose Escalation		From treatment initiation till study completion

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2021
• Primary Completion (Actual): February 13, 2025
• Study Completion (Actual): March 11, 2026

Study Registration Dates

• First Submitted: October 8, 2021
• First Submitted That Met QC Criteria: October 21, 2021
• First Posted (Actual): October 25, 2021

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: PF-06863135, Multiple Myeloma, BCMA, elranatamab, bispecific antibody, MagnetisMM-4
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Polycyclic Compounds; Piperidines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Dexamethasone; nirogacestat
• Other Study ID Numbers: C1071004; 2021-003885-11 (EudraCT Number); MAGNETISMM-4; Umbrella Study (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No