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

Multiple Myeloma Clinical Trial

— MagnetisMM-20  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05675449
• Other study ID #: C1071020
• Secondary ID: MAGNETISMM-20
• Status: Recruiting
• Phase: Phase 1
• Start date: December 14, 2022
• Est. completion date: March 19, 2028

Study information

• Verified date: June 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: March 19, 2028
• Est. primary completion date: May 11, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Elranatamab
BCMA-CD3 bispecific antibody
• Carfilzomib
proteasome inhibitor
• Maplirpacept
CD47-SIRP alpha-directed

Locations

Country	Name	City	State
Israel	Rambam Health Care Campus	Haifa
Israel	Division of Hematology Hadassah Medical Center - Ein Kerem	Jerusalem
Israel	Hadassah Medical Center - Ein Kerem	Jerusalem
Israel	Hematology Division Davidoff Center, Rabin Medical Center, Bellinson Hospital	Petach Tikvah
Israel	Hematology Division Davidoff Center, Rabin Medical Center, Beilinson Hospital	Petah Tikva
Israel	Hematology Division Davidoff Center, Rabin Medical Center, Beilinson Hospital	Petah Tikva
Israel	The Chaim Sheba Medical Center	Ramat-Gan
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
United States	Emory University Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University School of Medicine Investigational Drug Service	Atlanta	Georgia
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Sylvester Comprehensive Cancer Center - Aventura	Aventura	Florida
United States	Johns Hopkins Medicine	Baltimore	Maryland
United States	Oncology Investigational Drug Service,Department of Pharmacy Services	Baltimore	Maryland
United States	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Sylvester Comprehensive Cancer Center- The Lennar Foundation Medical Center	Coral Gables	Florida
United States	Sylvester Comprehensive Cancer Center - Coral Springs	Coral Springs	Florida
United States	University of Miami Hospital and Clinics - Deerfield Beach	Deerfield Beach	Florida
United States	Sylvester Comprehensive Cancer Center - Hollywood	Hollywood	Florida
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Sylvester Comprehensive Cancer Center - Kendall	Miami	Florida
United States	University of Miami Hospital And Clinics	Miami	Florida
United States	Henry-Joyce Cancer Clinic	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
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 - Main Campus	New York	New York
United States	Sylvester Comprehensive Cancer Center - Plantation	Plantation	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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.
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	Part 1: Concentrations of carfilzomib	Pre-dose and post-dose concentrations of cafilzomib	Once approximately 7 weeks from enrollment.
Secondary	Part 1: Concentrations of elranatamab	Pre-dose and post-dose concentrations of elranatamab	Assessed for approximately 2 years.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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.
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	Part 2A: Concentrations of maplirpacept	Pre-dose and post-dose concentrations of maplirpacept	Assessed for approximately 2 years.
Secondary	Part 2A: Concentrations of elranatamab	Pre-dose and post-dose concentrations of elranatamab	Assessed for approximately 2 years.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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.
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	Part 2B: Concentrations of maplirpacept	Pre-dose and post-dose concentrations of maplirpacept	Assessed for approximately 2 years.
Secondary	Part 2B: Concentrations of elranatamab	Pre-dose and post-dose concentrations of elranatamab	Assessed for approximately 2 years.
Secondary	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.
Secondary	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.

External Links

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