The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

Geo Regions

Category

Hematological Malignancies

Elranatamab

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
Phase 1
NCT05675449

Active enrolling

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Locations

United States, Israel

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Study design

Participant Group/Arm

EXPERIMENTAL: Part 1 Dose Escalation

Non randomized Elranatamab plus Carfilzomib and Dexamethasone

Intervention/Treatment

DRUG: Elranatamab

BCMA-CD3 bispecific antibody

DRUG: Carfilzomib

proteasome inhibitor
Participant Group/Arm

EXPERIMENTAL: Part 2A Dose Escalation

Non randomized Elranatamab plus Maplirpacept

Intervention/Treatment

DRUG: Elranatamab

BCMA-CD3 bispecific antibody

DRUG: Maplirpacept

CD47-SIRP alpha-directed
Participant Group/Arm

EXPERIMENTAL: Part 2B Dose Randomization

Randomized dose level Elranatamab plus Maplirpacept

Intervention/Treatment

DRUG: Elranatamab

BCMA-CD3 bispecific antibody

DRUG: Maplirpacept

CD47-SIRP alpha-directed
Study design table for Clinical Trial

Key eligibility criteria

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

    • Key dates

    Study start date
    • December 2022
    Estimated primary completion date
    • November 2027

    Key endpoints

    Primary Outcome Measures
    Outcome Measure

    Part 1 Number of participants with dose limiting toxicity (DLT)

    Measure Description

    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.

    Outcome Measure

    Part 2A Number of participants with dose limiting toxicity

    Measure Description

    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.

    Outcome Measure

    Part 2B Number of participants with dose limiting Toxicity

    Measure Description

    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.

    Primary Outcome Measures table for Clinical Trial
    Secondary Outcome Measures:
    Outcome Measure

    Part 1: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment

    Measure Description

    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.

    Outcome Measure

    Part 1: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity.

    Measure Description

    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.

    Outcome Measure

    Part 1: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities

    Measure Description

    Laboratory abnormalities as characterized by type, frequency, severity.

    Time Frame

    Accessed from baseline up to 90 days after the last dose of study treatment.

    Outcome Measure

    Part 1: Percent of participants with Best Overall Response (BOR)

    Measure Description

    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

    Outcome Measure

    Part 1: Percentage of Participants with an Objective Response Rate (ORR)

    Measure Description

    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.

    Outcome Measure

    Part 1: Percentage of participants with a complete response rate (CRR)

    Measure Description

    Complete Response/ stringent Complete Response (CR+sCR) rate per IMWG response criteria as determined by investigator.

    Time Frame

    Assessed for approximately 2 years

    Outcome Measure

    Part 1: Time to Response (TTR)

    Measure Description

    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.

    Outcome Measure

    Part 1: Duration of Response (DOR)

    Measure Description

    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.

    Outcome Measure

    Part 1: Duration of Complete Response (DOCR)

    Measure Description

    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.

    Outcome Measure

    Part 1: Time of Progression Free Survival (PFS)

    Measure Description

    Progression free survival (IMWG response criteria)

    Time Frame

    Assessed from enrollment until Progressive Disease or death for approximately 2 years.

    Outcome Measure

    Part 1: Time of Overall Survival (OS)

    Measure Description

    OS is the duration of time from first dose of study treatment to death.

    Time Frame

    Assessed for approximately 2 years

    Outcome Measure

    Part 1: Minimal Residual Disease (MRD) Negativity Rate

    Measure Description

    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

    Outcome Measure

    Part 1: Concentrations of carfilzomib

    Measure Description

    Pre-dose and post-dose concentrations of cafilzomib

    Time Frame

    Once approximately 7 weeks from enrollment.

    Outcome Measure

    Part 1: Concentrations of elranatamab

    Measure Description

    Pre-dose and post-dose concentrations of elranatamab

    Time Frame

    Assessed for approximately 2 years.

    Outcome Measure

    Part 1: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab

    Measure Description

    Percent of participants with positive ADA to elranatamab when given in combination with carfilzomib and dexamethasone

    Time Frame

    Assessed for approximately 2 years.

    Outcome Measure

    Part 2A: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment

    Measure Description

    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.

    Outcome Measure

    Part 2A: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity.

    Measure Description

    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.

    Outcome Measure

    Part 2A: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities

    Measure Description

    Laboratory abnormalities as characterized by type, frequency, severity.

    Time Frame

    Accessed from baseline up to 90 days after the last dose of study treatment.

    Outcome Measure

    Part 2A: Percent of participants with Best Overall Response (BOR)

    Measure Description

    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

    Outcome Measure

    Part 2A: Percentage of Participants with an Objective Response Rate (ORR)

    Measure Description

    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.

    Outcome Measure

    Part 2A: Percentage of participants with a complete response rate (CRR)

    Measure Description

    Complete Response/ stringent Complete Response (CR+sCR) rate per IMWG response criteria as determined by investigator.

    Time Frame

    Assessed for approximately 2 years

    Outcome Measure

    Part 2A: Time to Response (TTR)

    Measure Description

    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.

    Outcome Measure

    Part 2A: Duration of Response (DOR)

    Measure Description

    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.

    Outcome Measure

    Part 2A: Duration of Complete Response (DOCR)

    Measure Description

    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.

    Outcome Measure

    Part 2A: Time of Progression Free Survival (PFS)

    Measure Description

    Progression free survival (IMWG response criteria)

    Time Frame

    Assessed from enrollment until Progressive Disease or death for approximately 2 years.

    Outcome Measure

    Part 2A: Time of Overall Survival (OS)

    Measure Description

    OS is the duration of time from first dose of study treatment to death.

    Time Frame

    Assessed for approximately 2 years

    Outcome Measure

    Part 2A: Minimal Residual Disease (MRD) Negativity Rate

    Measure Description

    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

    Outcome Measure

    Part 2A: Concentrations of maplirpacept

    Measure Description

    Pre-dose and post-dose concentrations of maplirpacept

    Time Frame

    Assessed for approximately 2 years.

    Outcome Measure

    Part 2A: Concentrations of elranatamab

    Measure Description

    Pre-dose and post-dose concentrations of elranatamab

    Time Frame

    Assessed for approximately 2 years.

    Outcome Measure

    Part 2A: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab

    Measure Description

    Percent of participants with positive ADA to elranatamab when given in combination with maplirpacept

    Time Frame

    Assessed for approximately 2 years.

    Outcome Measure

    Part 2A: Percentage of participants with positive anti-drug antibodies (ADA) against maplirpacept

    Measure Description

    Percent of participants with positive ADA to elranatamab when given in combination with elranatamab

    Time Frame

    Assessed for approximately 2 years.

    Outcome Measure

    Part 2B: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment

    Measure Description

    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.

    Outcome Measure

    Part 2B: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity.

    Measure Description

    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.

    Outcome Measure

    Part 2B: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities

    Measure Description

    Laboratory abnormalities as characterized by type, frequency, severity.

    Time Frame

    Accessed from baseline up to 90 days after the last dose of study treatment.

    Outcome Measure

    Part 2B: Percent of participants with Best Overall Response (BOR)

    Measure Description

    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

    Outcome Measure

    Part 2B: Percentage of Participants with an Objective Response Rate (ORR)

    Measure Description

    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.

    Outcome Measure

    Part 2B: Percentage of participants with a complete response rate (CRR)

    Measure Description

    Complete Response/ stringent Complete Response (CR+sCR) rate per IMWG response criteria as determined by investigator.

    Time Frame

    Assessed for approximately 2 years

    Outcome Measure

    Part 2B: Time to Response (TTR)

    Measure Description

    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.

    Outcome Measure

    Part 2B: Duration of Response (DOR)

    Measure Description

    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.

    Outcome Measure

    Part 2B: Duration of Complete Response (DOCR)

    Measure Description

    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.

    Outcome Measure

    Part 2B: Time of Progression Free Survival (PFS)

    Measure Description

    Progression free survival (IMWG response criteria)

    Time Frame

    Assessed from enrollment until Progressive Disease or death for approximately 2 years.

    Outcome Measure

    Part 2B: Time of Overall Survival (OS)

    Measure Description

    OS is the duration of time from first dose of study treatment to death.

    Time Frame

    Assessed for approximately 2 years

    Outcome Measure

    Part 2B: Minimal Residual Disease (MRD) Negativity Rate

    Measure Description

    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

    Outcome Measure

    Part 2B: Concentrations of maplirpacept

    Measure Description

    Pre-dose and post-dose concentrations of maplirpacept

    Time Frame

    Assessed for approximately 2 years.

    Outcome Measure

    Part 2B: Concentrations of elranatamab

    Measure Description

    Pre-dose and post-dose concentrations of elranatamab

    Time Frame

    Assessed for approximately 2 years.

    Outcome Measure

    Part 2B: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab

    Measure Description

    Percent of participants with positive ADA to elranatamab when given in combination with maplirpacept

    Time Frame

    Assessed for approximately 2 years.

    Outcome Measure

    Part 2B: Percentage of participants with positive anti-drug antibodies (ADA) against maplirpacept

    Measure Description

    Percent of participants with positive ADA to elranatamab when given in combination with elranatamab

    Time Frame

    Assessed for approximately 2 years.

    Secondary Outcome Measures table for Clinical Trial

    Number of participants

    90

    Collaborators and investigators

    Sponsor: Pfizer

    Collaborator: None

    This information is current as of August 16th 2024.
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    When calling, please reference this study number:

    More Information Close NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier. NCT05675449