A Clinical Trial of Four Medicines (Elranatamab Plus Carfilzomib and Dexamethasone or Maplirpacept) in People With Relapsed Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT05675449
- Lead Sponsor
- Pfizer
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
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Prior diagnosis of multiple myeloma as defined by IMWG criteria.
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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).
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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.
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Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.
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Not pregnant or breastfeeding and willing to use contraception.
- 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.
- Part 1: Prior treatment with carfilzomib
- 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.
- Intolerance to or participants who have had a severe (Grade ≥3) allergic or anaphylactic reaction to antibodies or therapeutic proteins
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 Dose Escalation Elranatamab Non randomized Elranatamab plus Carfilzomib and Dexamethasone Part 1 Dose Escalation Carfilzomib Non randomized Elranatamab plus Carfilzomib and Dexamethasone Part 2B Dose Randomization Elranatamab Randomized dose level Elranatamab plus Maplirpacept Part 2B Dose Randomization Maplirpacept Randomized dose level Elranatamab plus Maplirpacept Part 2A Dose Escalation Elranatamab Non randomized Elranatamab plus Maplirpacept Part 2A Dose Escalation Maplirpacept Non randomized Elranatamab plus Maplirpacept
- Primary Outcome Measures
Name Time Method Part 1 Number of participants with dose limiting toxicity (DLT) From first dose of elranatamab through the end of the first cycle of combination treatment, about 42 days. Dose limiting toxicity rate based on dose limiting toxicity evaluable participants.
Part 2A Number of participants with dose limiting toxicity From the first dose of maplirpacept through the first cycle of combination treatment, about 64 days. Dose limiting toxicity based on dose limiting toxicity evaluable participants.
Part 2B Number of participants with dose limiting Toxicity From first dose of elranatamab through the first cycle of combination treatment, about 42 days. Dose limiting toxicity rate based on dose limiting toxicity evaluable participants.
- Secondary Outcome Measures
Name Time Method Part 1: Percentage of Participants with an Objective Response Rate (ORR) Assessed from enrollment for approximately 2 years. 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.
Part 1: Minimal Residual Disease (MRD) Negativity Rate Assessed for approximately 2 years 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.
Part 1: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity. Assessed from baseline up to 90 days after last dose of study treatment. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Part 1: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment Assessed from baseline up to 90 days after last dose of study 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.
Part 1: Percent of participants with Best Overall Response (BOR) Assessed for approximately 2 years BOR is defined as the best response recorded from treatment start until disease progression/recurrence based on International Myeloma Working Group (IMWG) response criteria.
Part 1: Percentage of participants with a complete response rate (CRR) Assessed for approximately 2 years Complete Response/ stringent Complete Response (CR+sCR) rate per IMWG response criteria as determined by investigator.
Part 1: Time of Overall Survival (OS) Assessed for approximately 2 years OS is the duration of time from first dose of study treatment to death.
Part 1: Concentrations of elranatamab Assessed for approximately 2 years. Pre-dose and post-dose concentrations of elranatamab
Part 1: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab Assessed for approximately 2 years. Percent of participants with positive ADA to elranatamab when given in combination with carfilzomib and dexamethasone
Part 1: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities Accessed from baseline up to 90 days after the last dose of study treatment. Laboratory abnormalities as characterized by type, frequency, severity.
Part 1: Time to Response (TTR) Assessed for approximately 2 years. 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.
Part 1: Duration of Response (DOR) Assessed for approximately 2 years. 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.
Part 1: Duration of Complete Response (DOCR) Assessed for approximately 2 years. 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.
Part 1: Time of Progression Free Survival (PFS) Assessed from enrollment until Progressive Disease or death for approximately 2 years. Progression free survival (IMWG response criteria)
Part 1: Concentrations of carfilzomib Once approximately 7 weeks from enrollment. Pre-dose and post-dose concentrations of cafilzomib
Part 2A: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment Assessed from baseline up to 90 days after last dose of study 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.
Part 2A: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity. Assessed from baseline up to 90 days after last dose of study treatment. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Part 2A: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities Accessed from baseline up to 90 days after the last dose of study treatment. Laboratory abnormalities as characterized by type, frequency, severity.
Part 2A: Percent of participants with Best Overall Response (BOR) Assessed for approximately 2 years BOR is defined as the best response recorded from treatment start until disease progression/recurrence based on International Myeloma Working Group (IMWG) response criteria.
Part 2A: Percentage of Participants with an Objective Response Rate (ORR) Assessed from enrollment for approximately 2 years. 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.
Part 2A: Percentage of participants with a complete response rate (CRR) Assessed for approximately 2 years Complete Response/ stringent Complete Response (CR+sCR) rate per IMWG response criteria as determined by investigator.
Part 2A: Time to Response (TTR) Assessed for approximately 2 years. 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.
Part 2A: Duration of Response (DOR) Assessed for approximately 2 years. 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.
Part 2A: Duration of Complete Response (DOCR) Assessed for approximately 2 years. 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.
Part 2A: Time of Progression Free Survival (PFS) Assessed from enrollment until Progressive Disease or death for approximately 2 years. Progression free survival (IMWG response criteria)
Part 2A: Time of Overall Survival (OS) Assessed for approximately 2 years OS is the duration of time from first dose of study treatment to death.
Part 2A: Minimal Residual Disease (MRD) Negativity Rate Assessed for approximately 2 years 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.
Part 2A: Concentrations of maplirpacept Assessed for approximately 2 years. Pre-dose and post-dose concentrations of maplirpacept
Part 2A: Concentrations of elranatamab Assessed for approximately 2 years. Pre-dose and post-dose concentrations of elranatamab
Part 2A: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab Assessed for approximately 2 years. Percent of participants with positive ADA to elranatamab when given in combination with maplirpacept
Part 2A: Percentage of participants with positive anti-drug antibodies (ADA) against maplirpacept Assessed for approximately 2 years. Percent of participants with positive ADA to elranatamab when given in combination with elranatamab
Part 2B: Time to Response (TTR) Assessed for approximately 2 years. 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.
Part 2B: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment Assessed from baseline up to 90 days after last dose of study 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.
Part 2B: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity. Assessed from baseline up to 90 days after last dose of study treatment. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Part 2B: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities Accessed from baseline up to 90 days after the last dose of study treatment. Laboratory abnormalities as characterized by type, frequency, severity.
Part 2B: Percent of participants with Best Overall Response (BOR) Assessed for approximately 2 years BOR is defined as the best response recorded from treatment start until disease progression/recurrence based on International Myeloma Working Group (IMWG) response criteria.
Part 2B: Percentage of Participants with an Objective Response Rate (ORR) Assessed from enrollment for approximately 2 years. 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.
Part 2B: Percentage of participants with a complete response rate (CRR) Assessed for approximately 2 years Complete Response/ stringent Complete Response (CR+sCR) rate per IMWG response criteria as determined by investigator.
Part 2B: Duration of Response (DOR) Assessed for approximately 2 years. 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.
Part 2B: Duration of Complete Response (DOCR) Assessed for approximately 2 years. 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.
Part 2B: Time of Progression Free Survival (PFS) Assessed from enrollment until Progressive Disease or death for approximately 2 years. Progression free survival (IMWG response criteria)
Part 2B: Time of Overall Survival (OS) Assessed for approximately 2 years OS is the duration of time from first dose of study treatment to death.
Part 2B: Minimal Residual Disease (MRD) Negativity Rate Assessed for approximately 2 years 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.
Part 2B: Concentrations of maplirpacept Assessed for approximately 2 years. Pre-dose and post-dose concentrations of maplirpacept
Part 2B: Concentrations of elranatamab Assessed for approximately 2 years. Pre-dose and post-dose concentrations of elranatamab
Part 2B: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab Assessed for approximately 2 years. Percent of participants with positive ADA to elranatamab when given in combination with maplirpacept
Part 2B: Percentage of participants with positive anti-drug antibodies (ADA) against maplirpacept Assessed for approximately 2 years. Percent of participants with positive ADA to elranatamab when given in combination with elranatamab
Trial Locations
- Locations (31)
Clinical Research Advisors (Encino Satellite Location)
🇺🇸Encino, California, United States
Clinical Research Advisors (Korea Town Satellite Location)
🇺🇸Los Angeles, California, United States
Clinical Research Advisors (West Hollywood Satellite Location)
🇺🇸Los Angeles, California, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
Sylvester Comprehensive Cancer Center - Aventura
🇺🇸Aventura, Florida, 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
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
University of Miami Hospital And Clinics
🇺🇸Miami, Florida, United States
Sylvester Comprehensive Cancer Center - Kendall
🇺🇸Miami, Florida, United States
Sylvester Comprehensive Cancer Center - Plantation
🇺🇸Plantation, Florida, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, 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
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
MSK Monmouth
🇺🇸Middletown, 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 - Main Campus
🇺🇸New York, New York, United States
Henry-Joyce Cancer Clinic
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Rambam Health Care Campus
🇮🇱Haifa, Israel
Division of Hematology Hadassah Medical Center - Ein Kerem
🇮🇱Jerusalem, 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, Israel