Clinical trial NCT05675449: A Clinical Trial of Four Medicines (Elranatamab Plus Carfilzomib and Dexamethasone or Maplirpacept) in People With Relapsed Refractory Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: elranatamab
relapsed
RRMM
BCMA
C1071020
MagnetisMM
maplipacelt
PF-06863135
carfilzomib
Bispecific antibody
PF-07901801
TTI-622
SIRPα
CD47
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-01-09
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Part 1 Number of participants with dose limiting toxicity (DLT)
timeFrame: From first dose of elranatamab through the end of the first cycle of combination treatment, about 42 days.
measure: Part 2A Number of participants with dose limiting toxicity
timeFrame: From the first dose of maplirpacept through the first cycle of combination treatment, about 64 days.
measure: Part 2B Number of participants with dose limiting Toxicity
timeFrame: From first dose of elranatamab through the first cycle of combination treatment, about 42 days.
Secondary outcomes:
measure: Part 1: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment
timeFrame: Assessed from baseline up to 90 days after last dose of study treatment.
measure: Part 1: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity.
timeFrame: Assessed from baseline up to 90 days after last dose of study treatment.
measure: Part 1: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities
timeFrame: Accessed from baseline up to 90 days after the last dose of study treatment.
measure: Part 1: Percent of participants with Best Overall Response (BOR)
timeFrame: Assessed for approximately 2 years
measure: Part 1: Percentage of Participants with an Objective Response Rate (ORR)
timeFrame: Assessed from enrollment for approximately 2 years.
measure: Part 1: Percentage of participants with a complete response rate (CRR)
timeFrame: Assessed for approximately 2 years
measure: Part 1: Time to Response (TTR)
timeFrame: Assessed for approximately 2 years.
measure: Part 1: Duration of Response (DOR)
timeFrame: Assessed for approximately 2 years.
measure: Part 1: Duration of Complete Response (DOCR)
timeFrame: Assessed for approximately 2 years.
measure: Part 1: Time of Progression Free Survival (PFS)
timeFrame: Assessed from enrollment until Progressive Disease or death for approximately 2 years.
measure: Part 1: Time of Overall Survival (OS)
timeFrame: Assessed for approximately 2 years
measure: Part 1: Minimal Residual Disease (MRD) Negativity Rate
timeFrame: Assessed for approximately 2 years
measure: Part 1: Concentrations of carfilzomib
timeFrame: Once approximately 7 weeks from enrollment.
measure: Part 1: Concentrations of elranatamab
timeFrame: Assessed for approximately 2 years.
measure: Part 1: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab
timeFrame: Assessed for approximately 2 years.
measure: Part 2A: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment
timeFrame: Assessed from baseline up to 90 days after last dose of study treatment.
measure: Part 2A: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity.
timeFrame: Assessed from baseline up to 90 days after last dose of study treatment.
measure: Part 2A: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities
timeFrame: Accessed from baseline up to 90 days after the last dose of study treatment.
measure: Part 2A: Percent of participants with Best Overall Response (BOR)
timeFrame: Assessed for approximately 2 years
measure: Part 2A: Percentage of Participants with an Objective Response Rate (ORR)
timeFrame: Assessed from enrollment for approximately 2 years.
measure: Part 2A: Percentage of participants with a complete response rate (CRR)
timeFrame: Assessed for approximately 2 years
measure: Part 2A: Time to Response (TTR)
timeFrame: Assessed for approximately 2 years.
measure: Part 2A: Duration of Response (DOR)
timeFrame: Assessed for approximately 2 years.
measure: Part 2A: Duration of Complete Response (DOCR)
timeFrame: Assessed for approximately 2 years.
measure: Part 2A: Time of Progression Free Survival (PFS)
timeFrame: Assessed from enrollment until Progressive Disease or death for approximately 2 years.
measure: Part 2A: Time of Overall Survival (OS)
timeFrame: Assessed for approximately 2 years
measure: Part 2A: Minimal Residual Disease (MRD) Negativity Rate
timeFrame: Assessed for approximately 2 years
measure: Part 2A: Concentrations of maplirpacept
timeFrame: Assessed for approximately 2 years.
measure: Part 2A: Concentrations of elranatamab
timeFrame: Assessed for approximately 2 years.
measure: Part 2A: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab
timeFrame: Assessed for approximately 2 years.
measure: Part 2A: Percentage of participants with positive anti-drug antibodies (ADA) against maplirpacept
timeFrame: Assessed for approximately 2 years.
measure: Part 2B: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment
timeFrame: Assessed from baseline up to 90 days after last dose of study treatment.
measure: Part 2B: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity.
timeFrame: Assessed from baseline up to 90 days after last dose of study treatment.
measure: Part 2B: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities
timeFrame: Accessed from baseline up to 90 days after the last dose of study treatment.
measure: Part 2B: Percent of participants with Best Overall Response (BOR)
timeFrame: Assessed for approximately 2 years
measure: Part 2B: Percentage of Participants with an Objective Response Rate (ORR)
timeFrame: Assessed from enrollment for approximately 2 years.
measure: Part 2B: Percentage of participants with a complete response rate (CRR)
timeFrame: Assessed for approximately 2 years
measure: Part 2B: Time to Response (TTR)
timeFrame: Assessed for approximately 2 years.
measure: Part 2B: Duration of Response (DOR)
timeFrame: Assessed for approximately 2 years.
measure: Part 2B: Duration of Complete Response (DOCR)
timeFrame: Assessed for approximately 2 years.
measure: Part 2B: Time of Progression Free Survival (PFS)
timeFrame: Assessed from enrollment until Progressive Disease or death for approximately 2 years.
measure: Part 2B: Time of Overall Survival (OS)
timeFrame: Assessed for approximately 2 years
measure: Part 2B: Minimal Residual Disease (MRD) Negativity Rate
timeFrame: Assessed for approximately 2 years
measure: Part 2B: Concentrations of maplirpacept
timeFrame: Assessed for approximately 2 years.
measure: Part 2B: Concentrations of elranatamab
timeFrame: Assessed for approximately 2 years.
measure: Part 2B: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab
timeFrame: Assessed for approximately 2 years.
measure: Part 2B: Percentage of participants with positive anti-drug antibodies (ADA) against maplirpacept
timeFrame: Assessed for approximately 2 years.
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Encino
country: United States
facility: Clinical Research Advisors (Encino Satellite Location)
state: California
city: Los Angeles
country: United States
facility: Clinical Research Advisors (Korea Town Satellite Location)
state: California
city: Los Angeles
country: United States
facility: Clinical Research Advisors (West Hollywood Satellite Location)
state: California
city: Aventura
country: United States
facility: Sylvester Comprehensive Cancer Center - Aventura
state: Florida
city: Coral Gables
country: United States
facility: Sylvester Comprehensive Cancer Center- The Lennar Foundation Medical Center
state: Florida
city: Coral Springs
country: United States
facility: Sylvester Comprehensive Cancer Center - Coral Springs
state: Florida
city: Deerfield Beach
country: United States
facility: University of Miami Hospital and Clinics - Deerfield Beach
state: Florida
city: Hollywood
country: United States
facility: Sylvester Comprehensive Cancer Center - Hollywood
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital And Clinics
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center - Kendall
state: Florida
city: Plantation
country: United States
facility: Sylvester Comprehensive Cancer Center - Plantation
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Baltimore
country: United States
facility: Oncology Investigational Drug Service,Department of Pharmacy Services
state: Maryland
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Middletown
country: United States
facility: MSK Monmouth
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care (74th Street).
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - Main Campus
state: New York
city: Nashville
country: United States
facility: Henry-Joyce Cancer Clinic
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Division of Hematology Hadassah Medical Center - Ein Kerem
city: Petah Tikva
country: Israel
facility: Hematology Division Davidoff Center, Rabin Medical Center, Beilinson Hospital
city: Ramat-Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: