Multiple Myeloma
Conditions
Keywords
elranatamab, relapsed, RRMM, BCMA, C1071020, MagnetisMM, maplipacelt, PF-06863135, carfilzomib, Bispecific antibody, PF-07901801, TTI-622, SIRPα, CD47
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.
Interventions
DRUGElranatamab
BCMA-CD3 bispecific antibody
DRUGCarfilzomib
proteasome inhibitor
DRUGMaplirpacept
CD47-SIRP alpha-directed
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
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. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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 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: 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 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: 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 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: 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: 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: Concentrations of carfilzomib | Once approximately 7 weeks from enrollment. | Pre-dose and post-dose concentrations of cafilzomib |
| 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 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: 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: 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: 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 |
Countries
Israel, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed