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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
90
BCMA-CD3 bispecific antibody
proteasome inhibitor
CD47-SIRP alpha-directed
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
RECRUITINGBeverly Hills Cancer Center
Beverly Hills, California, United States
RECRUITINGClinical Research Advisors (Encino Satellite Location)
Encino, California, United States
RECRUITINGClinical Research Advisors (Korea Town Satellite Location)
Los Angeles, California, United States
Part 1 Number of participants with dose limiting toxicity (DLT)
Dose limiting toxicity rate based on dose limiting toxicity evaluable participants.
Time frame: 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.
Time frame: 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.
Time frame: From first dose of elranatamab through the first cycle of combination treatment, about 42 days.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Assessed for approximately 2 years.
Part 1: Time of Progression Free Survival (PFS)
Progression free survival (IMWG response criteria)
Time frame: 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.
Time frame: 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.
Time frame: Assessed for approximately 2 years
Part 1: Concentrations of carfilzomib
Pre-dose and post-dose concentrations of cafilzomib
Time frame: Once approximately 7 weeks from enrollment.
Part 1: Concentrations of elranatamab
Pre-dose and post-dose concentrations of elranatamab
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Assessed for approximately 2 years.
Part 2A: Time of Progression Free Survival (PFS)
Progression free survival (IMWG response criteria)
Time frame: 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.
Time frame: 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.
Time frame: Assessed for approximately 2 years
Part 2A: Concentrations of maplirpacept
Pre-dose and post-dose concentrations of maplirpacept
Time frame: Assessed for approximately 2 years.
Part 2A: Concentrations of elranatamab
Pre-dose and post-dose concentrations of elranatamab
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Assessed for approximately 2 years.
Part 2B: Time of Progression Free Survival (PFS)
Progression free survival (IMWG response criteria)
Time frame: 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.
Time frame: 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.
Time frame: Assessed for approximately 2 years
Part 2B: Concentrations of maplirpacept
Pre-dose and post-dose concentrations of maplirpacept
Time frame: Assessed for approximately 2 years.
Part 2B: Concentrations of elranatamab
Pre-dose and post-dose concentrations of elranatamab
Time frame: 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
Time frame: 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
Time frame: Assessed for approximately 2 years.
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