A Study to Learn About the Study Medicine (Elranatamab) in Participants With Multiple Myeloma That Has Come Back After Responding to Treatment or Has Not Responded to Treatment

Phase 2

Active, not recruiting

• Conditions: Multiple Myeloma
• Interventions: Drug: Elranatamab

• Registration Number: NCT05014412
• Lead Sponsor: Pfizer

Brief Summary

The purpose of the study (Part 1 and Part 2) is to evaluate the safety of a step-up dosing approach (starting with low doses followed by higher doses) of the study medicine (elranatamab) in participants with multiple myeloma that has come back after responding to treatment or has not responded to treatment (relapsed/refractory multiple myeloma). This study will also look at the safety and efficacy of different doses of elranatamab, as well as different intervals between doses.

Participants in the study will receive elranatamab as an injection under the skin at the study clinic. After the initial step-up doses, participants will start receiving one dose every week. The frequency of clinic visits for injections may then decrease over time. Participation will be at least two years.

Detailed Description

The purpose of the study (Part 1 and Part 2) of the study is to evaluate the safety (in particular the rate of Grade ≥ 2 CRS) of a step-up priming dose regimen of elranatamab in participants with relapsed/refractory multiple myeloma. In addition, this study will assess the safety of different dosing regimens of elranatamab and if it can provide a clinical benefit in those participants. Elranatamab is a bispecific antibody: binding of elranatamab to CD3-expressing T-cells and BCMA-expressing multiple myeloma cells causes targeted T-cell-mediated cytotoxicity.

Study Timeline

• Study First Submitted: 2021-08-03
• Study First Submitted QC: 2021-08-17
• Study First Posted: 2021-08-20
• Study Start: 2021-10-07
• Primary Completion: 2023-06-15
• Results First Submitted: 2024-06-11
• Results First Submitted QC: 2024-07-29
• Results First Posted: 2024-07-30
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-10
• Last Update Posted: 2025-04-13
• Study Completion: 2025-05-17

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 86

Inclusion Criteria

• Diagnosis of multiple myeloma (IMWG criteria, Rajkumar et al, 2014)

• Measurable disease, as defined by at least 1 of the following:

  1. Serum M-protein >0.5 g/dL by SPEP
  2. Urinary M-protein excretion >200 mg/24 hours by UPEP
  3. Serum immunoglobulin FLC≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio

• Refractory to at least one IMiD

• Refractory to at least one PI

• Refractory to at least one anti-CD38 antibody

• Relapsed/refractory to last anti-myeloma regimen

• ECOG performance status ≤1

• 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
• POEMS syndrome
• Amyloidosis
• Waldenström's macroglobulinemia
• Known active CNS involvement or clinical signs of myelomatous meningeal involvement
• Stem cell transplant within 12 weeks prior to enrollment or active GVHD
• 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 or Stage 0/1 malignancy with minimal risk of recurrence per investigator.
• Previous treatment with an anti-BCMA bispecific antibody or CAR-T cell therapy.
• Live attenuated vaccine within 4 weeks of the first dose
• 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)
• Known or suspected hypersensitivity to the study intervention, or any of its excipients

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 2B	Elranatamab	Dose expansion
Part 1	Elranatamab	Evaluation of step-up priming dosing
Part 2A	Elranatamab	Dose determination
Part 2C	Elranatamab	To explore higher dose intensity

Primary Outcome Measures

Name	Time	Method
Number of Participants With Grade 2 or Higher Cytokine Release Syndrome (CRS) During Cycle 1: Parts 1 and 2	Parts 1 and 2: Cycle 1 (28 days)	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, Grade (G) 1: fever (temperature \>=38 degree Celsius), hypotension and/or hypoxia none; G 2: fever, hypotension not requiring vasopressors, hypoxia requiring low-flow nasal cannula/ facemask or blow-by; G 3: fever, hypotension requiring a vasopressor with or without vasopressin, hypoxia requiring high-flow nasal cannula/ facemask, nonrebreather mask, or Venturi mask; G 4: fever, hypotension requiring multiple vasopressors (excluding vasopressin), hypoxia requiring positive pressure. Organ toxicities associated with CRS graded according to CTCAE v5.0. G 1: Mild, G 2: Moderate, G 3: severe, and G 4: life-threatening consequences; urgent intervention indicated. G 5: death related to AE.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicities (DLTs): Part 2A	Part 2A: 28 days starting from the first 116 or 152 mg dose	Hematological: grade 4 neutropenia lasting \>5 days; febrile neutropenia; grade \>=3 neutropenia with infection; grade 4 thrombocytopenia; grade 3 thrombocytopenia with grade \>=2 bleeding. Non-hematological: grade \>=4 adverse events (AEs); grade 3 CRS (except CRS events: not been maximally treated or improved to grade \<=1 within 48 hours); grade 3 AEs (except: AEs attributed to a CRS event; grade 3 nausea, vomiting and diarrhea that improve to grade \<= 2 within 72 hours after maximal medical management has been initiated, grade 3 fatigue lasting \<1 week; grade 3 AEs that recover to baseline or grade 1 within 5 days); confirmed drug-induced liver injury meeting Hy's law criteria; grade 3-4 laboratory abnormalities; other clinically important or persistent AEs; Grade 3 injection site reaction. CTCAE version 5.0: Grade 1: Mild AE, Grade 2: Moderate, Grade 3: severe, and grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: death related to AE.
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [All Causalities and Treatment Related]: Parts 1 and 2	Day 1 of dosing up to 90 days post last dose (maximum treatment duration 25 cycles, follow up to 790 days)	An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose, meets 1 or more of the criteria listed below: Results in death, requires inpatient hospitalization or prolongation of existing hospitalization, life-threatening, congenital anomaly/birth defect etc. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator.
Number of Participants With Maximum Grade 3 or 4 and Grade 5 AEs [All Causalities and Treatment Related] Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5: Parts 1 and 2	Day 1 of dosing up to 90 days post last dose (maximum treatment duration 25 cycles, follow up to 790 days)	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. AEs were graded according to NCI CTCAE version 5.0 as Grade 1 indicates Mild AE, Grade 2 indicates Moderate AE, Grade 3 indicates severe AE, and grade 4 indicates life-threatening consequences; urgent intervention indicated. Grade 5 indicates death related to AE.
Number of Participants With Adverse Events of Special Interest (AESI)- CRS and Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) [All Causalities and Treatment Related]: Parts 1 and 2	Day 1 of dosing up to 90 days post last dose (maximum treatment duration 25 cycles, follow up to 790 days)	CRS and ICANS were assessed according to ASTCT criteria. ASTCT for ICANS: Grade 1 \[immune effector cell-associated encephalopathy (ICE, overall score range 0-10, higher score = better condition) score 7-9, awakens spontaneously\]; Grade 2 \[ICE score 3-6, awakens to voice\]; Grade 3 \[ICE score 0-2, awakens only to tactile stimulus, any clinical seizure that resolves rapidly or non-convulsive seizures on EEG that resolve with intervention, focal/local oedema on neuroimaging\]; Grade 4 \[ICE 0 (unarousable and unable to perform ICE), Unarousable or requires vigorous or repetitive tactile stimuli to arouse. Stupor or coma, Life-threatening prolonged seizure (\>5 min); or repetitive clinical or electrical seizures without return to baseline in between, deep focal motor weakness such as hemiparesis or paraparesis, Diffuse cerebral oedema on neuroimaging; decerebrate or decorticate posturing; or cranial nerve VI (abducens nerve) palsy; or papilledema; or Cushing's triad\].
Number of Participants With Hematological Measures With Baseline CTCAE Grade >=2 Shifted to a Maximum CTCAE Grade 3-4: Parts 1 and 2	Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)	Hematology results were graded according to the NCI CTCAE version 5.0 for relevant parameters, Grade 1 indicates Mild AE, Grade 2 indicates Moderate AE, Grade 3 indicates severe AE, and grade 4 indicates life-threatening consequences; urgent intervention indicated, Grade 5 indicates death related to AE. Hematological measures included Hemoglobin, Platelet count, WBC count, Plasma cell count. Absolute: Neutrophils, Eosinophils, Monocytes, Basophils, Lymphocytes, Plasma cells etc.
Number of Participants With Liver Function Tests Abnormalities: Parts 1 and 2	Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)	Alanine aminotransferase, aspartate aminotransferase, Alkaline Phosphatase, and total bilirubin (TBILI) were used to assess possible drug induced liver toxicity.
Time to Response (TTR) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2	Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)	Time to response 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: Parts 1 and 2	Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)	MRD negativity rate was defined as the percentage of participants with negative MRD (assessed by central laboratory) 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 occurred first. Sequencing MRD negative included: 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) 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.
Pre- and Post-dose Concentrations of Elranatamab: Parts 1 and 2	Parts 1 and 2: Till study completion approximately 3 years 7 months
Number of Participants With Anti-Drug Antibody (ADA) and Neutralizing Antibody (Nab) Against Elranatamab: Parts 1 and 2	Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)
Number of Participants With Clinical Chemistry Parameters With Baseline CTCAE Grade >=2 Shifted to a Maximum CTCAE Grade 3-4: Parts 1 and 2	Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)	Clinical chemistry data included BUN (Blood urea nitrogen), Creatinine, Glucose (non-fasting), Total Calcium, Sodium, Potassium, Chloride, Magnesium, Phosphorus or Phosphates, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Total bilirubin, Alkaline phosphatase, Albumin, Chloride, Total CO2 (bicarbonate), Total protein, Lactate dehydrogenase (LDH), Uric acid, Serum beta-2 microglobulin.
Objective Response Rate (ORR) Per International Myeloma Working Group (IMWG) Response Criteria as Determined by Investigator: Parts 1 and 2	Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)	ORR: % of participants with objective response. stringent complete response (sCR):CR; ii) normal serum free light chain (FLC) ratio; absence of clonal cells in bone marrow biopsy (BMB)/ bone marrow aspirate (BMA) by immunohistochemistry or immunofluorescence. 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 normal serum FLC ratio of 0.26-1.65. VGPR:Serum and urine M-protein detectable by immunofixation but not on electrophoresis;\>=90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 h; if only measurable disease is by serum FLC levels, VGPR:\>=90% decrease in difference between involved and uninvolved serum FLC levels; in addition if present at baseline, \>90% reduction compared to baseline in size of soft tissue plasmacytomas. PR:≥50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by ≥90% or to \<200 mg/24 h.
Complete Response Rate (CRR) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2	Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)	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).
Duration of Response (DOR) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2	Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)	DOR: time from the first documentation of objective response, until confirmed PD, or death due to any cause, whichever occurred first. PD: Increase of \>=25% from lowest confirmed response value in any 1 or more of following: serum M-component (absolute increase must be \>=0.5 g/dL); serum M-protein increase \>=1 g/dL, if lowest M component was \>=5 g/dL; urine M-protein (absolute increase must be \>=200 mg/24 h). In participants without measurable serum and urine M-protein levels, difference between involved and uninvolved serum FLC levels (absolute increase must be \>10 mg/dL). In participants without measurable serum, urine M-protein levels and involved serum FLC levels, BM plasma-cell % irrespective of baseline status (must be \>=10%). Appearance of a new lesion, \>=50% increase from nadir in SPD of \>1 lesion, or \>=50% increase in longest diameter of a previous lesion \>1 cm in short axis. \>=50% increase in circulating plasma cells (minimum of 200 cells per mcL) if only measure of disease.
Duration of Complete Response Rate (DOCR) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2	Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)	DOCR was defined as the time from the first documentation of sCR or CR that was subsequently confirmed, until confirmed PD per IMWG criteria, or death due to any cause, whichever occurred first. 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).
Progression Free Survival (PFS) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2	Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)	PFS was defined as the time from the date of first dose until confirmed PD per IMWG criteria, or death due to any cause, whichever occurred first. Analysis was performed using Kaplan-Meier method. Participants with no PD event or death or who started a new anticancer therapy prior to an event or with an event after a gap of 2 or more missing disease assessments were censored on the date of last adequate disease assessment. Participants who did not have an adequate post-baseline disease assessment were censored on the date of first dose of study intervention unless death occurred on or before the time of the second planned disease assessment (\<=8 weeks after the date of first dose) in which case the death was considered an event.
Overall Survival (OS): Parts 1 and 2	Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)	OS was defined as the time from the date of first dose until death due to any cause. If a participant was not known to have died, survival was censored at the date of last contact. Analysis was performed using Kaplan-Meier method.

Trial Locations

Locations (38)

Mayo Clinic Hospital; 🇺🇸 Phoenix, Arizona, United States

Mayo Clinic; 🇺🇸 Scottsdale, Arizona, United States

Poudre Valley Hospital; 🇺🇸 Fort Collins, Colorado, United States

Cancer Care & Hematology - Fort Collins; 🇺🇸 Fort Collins, Colorado, United States

UCHealth Cancer Care & Hematology - Greeley; 🇺🇸 Greeley, Colorado, United States

UCHealth Cancer Care & Hematology - Loveland; 🇺🇸 Loveland, Colorado, United States

UF Health Shands Cancer Hospital; 🇺🇸 Gainesville, Florida, United States

UF Health Shands Hospital Pharmacy Investigational Drug Service - Main; 🇺🇸 Gainesville, Florida, United States

UF Health Shands Hospital; 🇺🇸 Gainesville, Florida, United States

East Jefferson General Hospital Bone Marrow Transplant Clinic; 🇺🇸 Metairie, Louisiana, United States

East Jefferson General Hospital; 🇺🇸 Metairie, Louisiana, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

MSK Bergen; 🇺🇸 Montvale, New Jersey, United States

Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care (74th Street).; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

MSK Nassau; 🇺🇸 Uniondale, New York, United States

Cleveland Clinic Taussig Cancer Institute; 🇺🇸 Cleveland, Ohio, United States

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

St. David's South Austin Medical Center; 🇺🇸 Austin, Texas, United States

Blood Cancer and Stem Cell Transplant Clinic; 🇺🇸 San Antonio, Texas, United States

Methodist Healthcare System of San Antonio dba Methodist Hospital; 🇺🇸 San Antonio, Texas, United States

Methodist Hospital Investigational Pharmacy; 🇺🇸 San Antonio, Texas, United States

Methodist Plaza Clinical Trials Office; 🇺🇸 San Antonio, Texas, United States

Huntsman Cancer Institute, University of Utah; 🇺🇸 Salt Lake City, Utah, United States

Nagoya City University Hospital; 🇯🇵 Nagoya, Aichi, Japan

Kobe City Medical Center General Hospital; 🇯🇵 Kobe-city, Hyogo, Japan

National Cancer Center Hospital; 🇯🇵 Chuo-ku, Tokyo, Japan

Japanese Red Cross Medical Center; 🇯🇵 Shibuya-ku, Tokyo, Japan

University Hospital,Kyoto Prefectural University of Medicine; 🇯🇵 Kyoto, Japan

China Medical University Hospital; 🇨🇳 Taichung, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei City, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

The Royal Marsden NHS Foundation Trust; 🇬🇧 Sutton, Surrey, United Kingdom

University Hospitals Birmingham NHS Foundation Trust; 🇬🇧 Birmingham, United Kingdom

Guy's and St Thomas' NHS Foundation Trust; 🇬🇧 London, United Kingdom

King's College Hospital NHS Foundation Trust; 🇬🇧 London, United Kingdom

University College London Hospitals NHS Foundation Trust NIHR; 🇬🇧 London, United Kingdom