A Clinical Trial of Four Medicines (Elranatamab Plus Carfilzomib and Dexamethasone or Maplirpacept) in People With Relapsed Refractory Multiple Myeloma (MagnetisMM-20)

A PHASE 1B, OPEN-LABEL STUDY OF ELRANATAMAB IN COMBINATION WITH CARFILZOMIB PLUS DEXAMETHASONE AND ELRANATAMAB IN COMBINATION WITH PF-07901801 IN PARTICIPANTS WITH RELAPSED REFRACTORY MULTIPLE MYELOMA

The main purpose of the study is to evaluate the safety and tolerability of the combination of elranatamab and carfilzomib and dexamethasone or elranatamab and maplirpacept.

There are 2 parts to this study. Part 1 will evaluate the safety and tolerability of elranatamab when given in combination with carfilzomib plus dexamethasone. Part 2 has 2 arms. The first will evaluate the safety and tolerability of elranatamab when given in combination with maplirpacept. The second will identify the optimal dose(s) of elranatamab plus maplirpacept.

All study medicines are given over 4-week cycles. Everyone taking part in this study will receive elranatamab as a shot under the skin. Participants in Part 1 will also receive weekly carfilzomib as an IV infusion (given directly into a vein) and dexamethasone either by mouth (as a pill) or by IV infusion. Participants in Part 2 will receive elranatamab in combination with maplirpacept as an IV infusion (given directly into a vein)

The investigators will examine the experiences of people receiving the study medicines. This will help determine if the study medicines are safe and can be used for multiple myeloma treatment. Participants will take part in this study for about 2 years after the first dose.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Elranatamab; Drug: Carfilzomib; Drug: Maplirpacept

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• Israel
  • Haifa, Israel, 3109601
    • Not yet recruiting
    • Rambam Health Care Campus
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Medical Center - Ein Kerem
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Division of Hematology Hadassah Medical Center - Ein Kerem
  • Petach Tikvah, Israel, 4941494
    • Not yet recruiting
    • Hematology Division Davidoff Center, Rabin Medical Center, Bellinson Hospital
  • Petah Tikva, Israel, 4941494
    • Not yet recruiting
    • Hematology Division Davidoff Center, Rabin Medical Center, Beilinson Hospital
  • Petah Tikva, Israel, 4941492
    • Not yet recruiting
    • Hematology Division Davidoff Center, Rabin Medical Center, Beilinson Hospital
  • Ramat-Gan, Israel, 5265601
    • Not yet recruiting
    • The Chaim Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Not yet recruiting
    • Tel-Aviv Sourasky Medical Center
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Not yet recruiting
      • University of Arkansas for Medical Sciences
  • California
    • Beverly Hills, California, United States, 90211
      • Recruiting
      • Beverly Hills Cancer Center
  • Florida
    • Aventura, Florida, United States, 33180
      • Recruiting
      • Sylvester Comprehensive Cancer Center - Aventura
    • Coral Gables, Florida, United States, 33146
      • Recruiting
      • Sylvester Comprehensive Cancer Center- The Lennar Foundation Medical Center
    • Coral Springs, Florida, United States, 33065
      • Recruiting
      • Sylvester Comprehensive Cancer Center - Coral Springs
    • Deerfield Beach, Florida, United States, 33442
      • Recruiting
      • University of Miami Hospital and Clinics - Deerfield Beach
    • Hollywood, Florida, United States, 33021
      • Recruiting
      • Sylvester Comprehensive Cancer Center - Hollywood
    • Miami, Florida, United States, 33136
      • Recruiting
      • Sylvester Comprehensive Cancer Center
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami Hospital and Clinics
    • Miami, Florida, United States, 33176
      • Recruiting
      • Sylvester Comprehensive Cancer Center - Kendall
    • Plantation, Florida, United States, 33324
      • Recruiting
      • Sylvester Comprehensive Cancer Center - Plantation
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30308
      • Not yet recruiting
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Winship Cancer Institute
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospitals and Clinics
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Medicine
    • Baltimore, Maryland, United States, 21231
      • Recruiting
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Baltimore, Maryland, United States, 21231
      • Recruiting
      • Oncology Investigational Drug Service,Department of Pharmacy Services
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10065
      • Not yet recruiting
      • Memorial Sloan Kettering Cancer Center - Main Campus
    • New York, New York, United States, 10021
      • Not yet recruiting
      • Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care (74th Street).

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Prior diagnosis of multiple myeloma as defined by IMWG criteria.

• Measurable disease based on IMWG criteria 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 (<0.26 or >1.65).
• Part 1: Received at least 1 but not more than 3 prior lines of therapy for multiple myeloma (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy).
• Part 2: Received at least 3 prior lines of therapy for multiple myeloma who are refractory to at least one IMiD, one PI and one anti-CD38 antibody.
• ECOG performance status 0-1.
• Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.
• Not pregnant or breastfeeding and willing to use contraception.
• Prior therapy with carfilzomib is allowed as long as the participant had (all apply): responded to most recent therapy with carfilzomib; Carfilzomib was not discontinued due to toxicity; Did not relapse within 60 days from discontinuation of carfilzomib; Will have at least a 6-month carfilzomib treatment-free interval from last dose received until first study treatment.

Exclusion Criteria:

• Plasma cell leukemia, Smouldering MM, Waldenströms macroglobulinemia, Amyloidosis, POEMS Syndrome, Primary refractory MM
• Impaired cardiovascular function or clinically significant cardiovascular diseases.
• Participants with any active, uncontrolled bacterial, fungal, or viral infection.
• Stem cell transplant within 12 weeks prior to enrollment, or active graft versus host disease.
• 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.
• Part 1: Previous treatment with a BCMA-directed therapy.
• Part 2: Previous treatment with any anti-BCMA directed therapy, with the exception of CAR-T. Previous treatment with a CD47-SIRP alpha-directed therapy.
• Live attenuated vaccine within 4 weeks of the first dose of study intervention.
• Administration with an investigational product (e.g. drug or vaccine) concurrent with study intervention or within 30 days preceding the first dose of study intervention used in this study.
• Any of the following within 3 months of enrollment: erosive esophagitis, treatment resistant peptic ulcer, infectious or inflammatory bowel disease, pulmonary embolism or uncontrolled thromboembolic event.
• Participants who are unable to tolerate carfilzomib due to suspected carfilzomib-related congestive heart failure or thrombotic microangiopathy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Dose Escalation; Non randomized Elranatamab plus Carfilzomib and Dexamethasone	Drug: Elranatamab; BCMA-CD3 bispecific antibody; Other Names: PF-06863135; Drug: Carfilzomib; proteasome inhibitor; Other Names: Kyprolis
Experimental: Part 2A Dose Escalation; Non randomized Elranatamab plus Maplirpacept	Drug: Elranatamab; BCMA-CD3 bispecific antibody; Other Names: PF-06863135; Drug: Maplirpacept; CD47-SIRP alpha-directed; Other Names: PF-07901801, TTI-622
Experimental: Part 2B Dose Randomization; Randomized dose level Elranatamab plus Maplirpacept	Drug: Elranatamab; BCMA-CD3 bispecific antibody; Other Names: PF-06863135; Drug: Maplirpacept; CD47-SIRP alpha-directed; Other Names: PF-07901801, TTI-622

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 Number of participants with dose limiting toxicity (DLT)	Dose limiting toxicity rate based on dose limiting toxicity evaluable participants.	From first dose of elranatamab through the end of the first cycle of combination treatment, about 42 days.
Part 2A Number of participants with dose limiting toxicity	Dose limiting toxicity based on dose limiting toxicity evaluable participants.	From the first dose of maplirpacept through the first cycle of combination treatment, about 64 days.
Part 2B Number of participants with dose limiting Toxicity	Dose limiting toxicity rate based on dose limiting toxicity evaluable participants.	From first dose of elranatamab through the first cycle of combination treatment, about 42 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment	Counts of participants who had TEAEs, defined as newly occurring or worsening after first dose. Relatedness to study drug was assessed by the investigator. Participants with multiple occurrences of an AE within a category were counted once within the category.	Assessed from baseline up to 90 days after last dose of study treatment.
Part 1: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity.	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	Assessed from baseline up to 90 days after last dose of study treatment.
Part 1: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities	Laboratory abnormalities as characterized by type, frequency, severity.	Accessed from baseline up to 90 days after the last dose of study treatment.
Part 1: Percent of participants with Best Overall Response (BOR)	BOR is defined as the best response recorded from treatment start until disease progression/recurrence based on International Myeloma Working Group (IMWG) response criteria.	Assessed for approximately 2 years
Part 1: Percentage of Participants with an Objective Response Rate (ORR)	ORR rate is defined as the percent of participants having a Best Overall Response (BOR) of confirmed Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR) according to IMWG.	Assessed from enrollment for approximately 2 years.
Part 1: Percentage of participants with a complete response rate (CRR)	Complete Response/ stringent Complete Response (CR+sCR) rate per IMWG response criteria as determined by investigator.	Assessed for approximately 2 years
Part 1: Time to Response (TTR)	TTR is 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.	Assessed for approximately 2 years.
Part 1: Duration of Response (DOR)	DOR is defined, for participants with an objective response per IMWG criteria, as the time from the first documentation of objective response that is subsequently confirmed, until the first documentation of confirmed progressive disease (PD) per IMWG criteria.	Assessed for approximately 2 years.
Part 1: Duration of Complete Response (DOCR)	DOCR is defined, for participants with a Complete Response/stringent Complete Response (CR+sCR) per IMWG criteria, as the time from the first documentation of CR/sCR that is subsequently confirmed, until the first documentation of confirmed progressive disease (PD) per IMWG criteria.	Assessed for approximately 2 years.
Part 1: Time of Progression Free Survival (PFS)	Progression free survival (IMWG response criteria)	Assessed from enrollment until Progressive Disease or death for approximately 2 years.
Part 1: Time of Overall Survival (OS)	OS is the duration of time from first dose of study treatment to death.	Assessed for approximately 2 years
Part 1: Minimal Residual Disease (MRD) Negativity Rate	MRD negativity rate is the proportion of participants acheiving CR+sCR with negative MRD, per IMWG sequencing criteria, from the date of first dose until the first documentation of confirmed progressive disease (PD), death or start of new anticancer therapy.	Assessed for approximately 2 years
Part 1: Concentrations of carfilzomib	Pre-dose and post-dose concentrations of cafilzomib	Once approximately 7 weeks from enrollment.
Part 1: Concentrations of elranatamab	Pre-dose and post-dose concentrations of elranatamab	Assessed for approximately 2 years.
Part 1: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab	Percent of participants with positive ADA to elranatamab when given in combination with carfilzomib and dexamethasone	Assessed for approximately 2 years.
Part 2A: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment	Counts of participants who had TEAEs, defined as newly occurring or worsening after first dose. Relatedness to study drug was assessed by the investigator. Participants with multiple occurrences of an AE within a category were counted once within the category.	Assessed from baseline up to 90 days after last dose of study treatment.
Part 2A: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity.	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	Assessed from baseline up to 90 days after last dose of study treatment.
Part 2A: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities	Laboratory abnormalities as characterized by type, frequency, severity.	Accessed from baseline up to 90 days after the last dose of study treatment.
Part 2A: Percent of participants with Best Overall Response (BOR)	BOR is defined as the best response recorded from treatment start until disease progression/recurrence based on International Myeloma Working Group (IMWG) response criteria.	Assessed for approximately 2 years
Part 2A: Percentage of Participants with an Objective Response Rate (ORR)	ORR rate is defined as the percent of participants having a Best Overall Response (BOR) of confirmed Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR) according to IMWG.	Assessed from enrollment for approximately 2 years.
Part 2A: Percentage of participants with a complete response rate (CRR)	Complete Response/ stringent Complete Response (CR+sCR) rate per IMWG response criteria as determined by investigator.	Assessed for approximately 2 years
Part 2A: Time to Response (TTR)	TTR is 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.	Assessed for approximately 2 years.
Part 2A: Duration of Response (DOR)	DOR is defined, for participants with an objective response per IMWG criteria, as the time from the first documentation of objective response that is subsequently confirmed, until the first documentation of confirmed progressive disease (PD) per IMWG criteria.	Assessed for approximately 2 years.
Part 2A: Duration of Complete Response (DOCR)	DOCR is defined, for participants with a Complete Response/stringent Complete Response (CR+sCR) per IMWG criteria, as the time from the first documentation of CR/sCR that is subsequently confirmed, until the first documentation of confirmed progressive disease (PD) per IMWG criteria.	Assessed for approximately 2 years.
Part 2A: Time of Progression Free Survival (PFS)	Progression free survival (IMWG response criteria)	Assessed from enrollment until Progressive Disease or death for approximately 2 years.
Part 2A: Time of Overall Survival (OS)	OS is the duration of time from first dose of study treatment to death.	Assessed for approximately 2 years
Part 2A: Minimal Residual Disease (MRD) Negativity Rate	MRD negativity rate is the proportion of participants achieving CR+sCR with negative MRD, per IMWG sequencing criteria, from the date of first dose until the first documentation of confirmed progressive disease (PD), death or start of new anticancer therapy.	Assessed for approximately 2 years
Part 2A: Concentrations of maplirpacept	Pre-dose and post-dose concentrations of maplirpacept	Assessed for approximately 2 years.
Part 2A: Concentrations of elranatamab	Pre-dose and post-dose concentrations of elranatamab	Assessed for approximately 2 years.
Part 2A: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab	Percent of participants with positive ADA to elranatamab when given in combination with maplirpacept	Assessed for approximately 2 years.
Part 2A: Percentage of participants with positive anti-drug antibodies (ADA) against maplirpacept	Percent of participants with positive ADA to elranatamab when given in combination with elranatamab	Assessed for approximately 2 years.
Part 2B: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment	Counts of participants who had TEAEs, defined as newly occurring or worsening after first dose. Relatedness to study drug was assessed by the investigator. Participants with multiple occurrences of an AE within a category were counted once within the category.	Assessed from baseline up to 90 days after last dose of study treatment.
Part 2B: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity.	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	Assessed from baseline up to 90 days after last dose of study treatment.
Part 2B: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities	Laboratory abnormalities as characterized by type, frequency, severity.	Accessed from baseline up to 90 days after the last dose of study treatment.
Part 2B: Percent of participants with Best Overall Response (BOR)	BOR is defined as the best response recorded from treatment start until disease progression/recurrence based on International Myeloma Working Group (IMWG) response criteria.	Assessed for approximately 2 years
Part 2B: Percentage of Participants with an Objective Response Rate (ORR)	ORR rate is defined as the percent of participants having a Best Overall Response (BOR) of confirmed Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR) according to IMWG.	Assessed from enrollment for approximately 2 years.
Part 2B: Percentage of participants with a complete response rate (CRR)	Complete Response/ stringent Complete Response (CR+sCR) rate per IMWG response criteria as determined by investigator.	Assessed for approximately 2 years
Part 2B: Time to Response (TTR)	TTR is 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.	Assessed for approximately 2 years.
Part 2B: Duration of Response (DOR)	DOR is defined, for participants with an objective response per IMWG criteria, as the time from the first documentation of objective response that is subsequently confirmed, until the first documentation of confirmed progressive disease (PD) per IMWG criteria.	Assessed for approximately 2 years.
Part 2B: Duration of Complete Response (DOCR)	DOCR is defined, for participants with a Complete Response/stringent Complete Response (CR+sCR) per IMWG criteria, as the time from the first documentation of CR/sCR that is subsequently confirmed, until the first documentation of confirmed progressive disease (PD) per IMWG criteria.	Assessed for approximately 2 years.
Part 2B: Time of Progression Free Survival (PFS)	Progression free survival (IMWG response criteria)	Assessed from enrollment until Progressive Disease or death for approximately 2 years.
Part 2B: Time of Overall Survival (OS)	OS is the duration of time from first dose of study treatment to death.	Assessed for approximately 2 years
Part 2B: Minimal Residual Disease (MRD) Negativity Rate	MRD negativity rate is the proportion of participants achieving CR+sCR with negative MRD, per IMWG sequencing criteria, from the date of first dose until the first documentation of confirmed progressive disease (PD), death or start of new anticancer therapy.	Assessed for approximately 2 years
Part 2B: Concentrations of maplirpacept	Pre-dose and post-dose concentrations of maplirpacept	Assessed for approximately 2 years.
Part 2B: Concentrations of elranatamab	Pre-dose and post-dose concentrations of elranatamab	Assessed for approximately 2 years.
Part 2B: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab	Percent of participants with positive ADA to elranatamab when given in combination with maplirpacept	Assessed for approximately 2 years.
Part 2B: Percentage of participants with positive anti-drug antibodies (ADA) against maplirpacept	Percent of participants with positive ADA to elranatamab when given in combination with elranatamab	Assessed for approximately 2 years.

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): December 14, 2022
• Primary Completion (Estimated): August 19, 2025
• Study Completion (Estimated): November 20, 2027

Study Registration Dates

• First Submitted: December 7, 2022
• First Submitted That Met QC Criteria: December 21, 2022
• First Posted (Actual): January 9, 2023

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: RRMM; relapsed; PF-06863135; BCMA; CD47; Bispecific antibody; MagnetisMM; SIRPα; TTI-622; carfilzomib; elranatamab; C1071020; PF-07901801; maplipacelt
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: C1071020; MAGNETISMM-20 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• 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