MagnetisMM-4: Umbrella Study of Elranatamab (PF-06863135) in Combination With Anti-Cancer Treatments in Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT05090566
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this study is to determine the Recommended Phase 2 Dose and clinical benefit of elranatamab in combination with other anti-cancer therapies in participants with multiple myeloma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
-
Relapsed/refractory multiple myeloma with at least 3 prior lines of therapy
-
Refractory to at least one IMiD, one proteasome inhibitor, and one anti-CD38 antibody
-
Measurable disease defined by at least one of the following:
- Serum M-protein >/= 0.5 g/dL by SPEP
- Urinary M-protein excretion >/= 200 mg/24 hours by UPEP
- Serum immunoglobulin FLC >/= 10 mg/dL (>/= 100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio
-
ECOG performance status 0 -1
-
Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade </= 1
- Active plasma cell leukemia
- Amyloidosis
- Stem cell transplant with 12 weeks prior to enrollment, or active GVHD
- POEMS syndrome
- Any active uncontrolled bacterial, fungal, or viral infection
- Impaired cardiovascular function or clinically significant cardiovascular diseases within 6 months prior to enrollment
- Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of study treatment (whichever is longer)
- Sub-Study A Only: Previous treatment with BCMA bispecific antibody
- Sub-Study B Only: Previous treatment with BCMA directed therapy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sub-Study B Elranatamab + lenalidomide + dexamethasone BCMA-CD3 bispecific antibody + immunomodulatory drug Sub-Study A Elranatamab + Nirogacestat BCMA-CD3 bispecific antibody + gamma secretase inhibitor
- Primary Outcome Measures
Name Time Method Sub-Study B Phase 1 Escalation: Dose Limiting Toxicity approximately 42 days Number of participants with Dose Limiting Toxicity
Sub-Study A Phase 1: Dose Limiting Toxicity approximately 35 days Number of participants with Dose Limiting Toxicity
Sub-Study A Phase 2: Objective Response Rate assessed every 4 weeks (for approximately 2 years) Objective response rate (IMWG response criteria)
- Secondary Outcome Measures
Name Time Method Sub-Study A Phase 1 and Phase 2: Complete Response Rate assessed every 4 weeks (for approximately 2 years) Complete response rate (IMWG response criteria)
Sub-Study B Phase 1 Escalation: Progression Free Survival assessed every 4 weeks (for approximately 2 years) Progression free survival (IMWG response criteria)
Sub-Study A Phase 1: Objective Response Rate assessed every 4 weeks (for approximately 2 years) Objective response rate (IMWG response criteria)
Sub-Study A Phase 1 and Phase 2: Duration of Complete Response assessed every 4 weeks (for approximately 2 years) Duration of complete response (IMWG response criteria)
Sub-Study A Phase 1: Time to Maximum Concentration (Tmax) for elranatamab assessed after first elranatamab dose (approximately 3-7 days) Tmax for elranatamab administration
Sub-Study A Phase 1 and 2: Duration of Response assessed every 4 weeks (for approximately 2 years) Duration of response (IMWG response criteria)
Sub-Study A Phase 1 and Phase 2: Minimal Residual Disease Negativity Rate assessed approximately every 12 months (for approximately 2 years) Minimal residual disease negativity rate (IMWG response criteria)
Sub-Study A Phase 1: Maximum Observed Concentration (Cmax) for elranatamab assessed after first elranatamab dose (approximately 3-7 days) Cmax for elranatamab administration
Sub-Study A Phase 1: Area Under the Concentration versus Time Curve from Time 0 to the Last Measurable Concentration (AUClast) for elranatamab assessed after first elranatamab dose (approximately 3-7 days) AUClast for elranatamab administration
Sub-Study B Phase 1 Escalation: Frequency of Treatment-Emergent Adverse Events assessed for approximately 2 years Type and severity per NCI CTCAE v5 (CRS and ICANS assessed per ASTCT criteria)
Sub-Study B Phase 1 Escalation: Duration of Response assessed every 4 weeks (for approximately 2 years) Duration of response (IMWG response criteria)
Sub-Study B Phase 1 Escalation: Immunogenicity of elranatamab in combination with lenalidomide assessed approximately every 1 to 3 cycles (each cycle approximately 28 days) Anti-drug antibodies and neutralizing antibodies against elranatamab
Sub-Study A Phase 1 and Phase 2: Overall Survival assessed for approximately 2 years Overall survival
Sub-Study A Phase 1 and Phase 2: Frequency of Treatment-Emergent Adverse Events assessed for approximately 2 years Type and severity per NCI CTCAE v5 (CRS and ICANS assessed per ASTCT criteria)
Sub-Study A Phase 1 and Phase 2: Concentrations of elranatamab and/or nirogacestat assessed approximately every 1 to 3 cycles (each cycle approximately 28 days) Pre-dose and post-dose concentrations of elranatamab; pre-dose concentrations of nirogacestat
Sub-Study B Phase 1 Escalation: Frequency of Laboratory Abnormalities assessed every cycle (each cycle approximately 28 days) Type and severity per NCI CTCAE v5
Sub-Study B Phase 1 Escalation: Objective Response Rate assessed every 4 weeks (for approximately 2 years) Objective response rate (IMWG response criteria)
Sub-Study B Phase 1 Escalation: Minimal Residual Disease Negativity Rate assessed approximately every 12 months (for approximately 2 years) Minimal residual disease negativity ratio (IMWG response criteria)
Sub-Study B Phase 1 Escalation: Time to Maximum Concentration (Tmax) for elranatamab assessed after first elranatamab dose (approximately 3-7 days) Tmax for elranatamab administration
Sub-Study A Phase 1 and Phase 2: Time to Response assessed every 4 weeks (for approximately 2 years) Time to response (IMWG criteria)
Sub-Study A Phase 1 and Phase 2: Progression Free Survival assessed every 4 weeks (for approximately 2 years) Progression free survival (IMWG response criteria)
Sub-Study A Phase 1 and Phase 2: Frequency of Laboratory Abnormalities assessed every cycle (each cycle approximately 28 days) Type and severity per NCI CTCAE v5
Sub-Study A Phase 1 and Phase 2: Immunogenicity of elranatamab in combination with nirogacestat assessed approximately every 1 to 3 cycles (each cycle approximately 28 days) Anti-drug antibodies and neutralizing antibodies against elranatamab
Sub-Study B Phase 1 Escalation: Time to Response assessed every 4 weeks (for approximately 2 years) Time to response (IMWG criteria)
Sub-Study B Phase 1 Escalation: Duration of Complete Response assessed every 4 weeks (for approximately 2 years) Duration of complete response (IMWG response criteria)
Sub-Study B Phase 1 Escalation: Overall Survival assessed for approximately 2 years Overall survival
Sub-Study B Phase 1 Escalation: Maximum Observed Concentrations (Cmax) for elranatamab assessed after first elranatamab dose (approximately 3-7 days) Cmax for elranatamab administration
Sub-Study B Phase 1 Escalation: Complete Response Rate assessed every 4 weeks (for approximately 2 years) Complete response rate (IMWG response criteria)
Sub-Study B Phase 1 Escalation: Concentrations of elranatamab and/or lenalidomide assessed approximately every 1 to 3 cycles (each cycle approximately 28 days) Pre-dose and post-dose concentrations of elranatamab, pre-dose concentrations of lenalidomide
Sub-Study B Phase 1 Escalation: Area Under the Concentration versus Time Curve from Time 0 to the Last Measurable Concentration (AUClast) for elranatamab assessed after first elranatamab dose (approximately 3-7 days) AUClast for elranatamab administration
Trial Locations
- Locations (40)
Cedars-Sinai Tarzana
🇺🇸Tarzana, California, United States
Banner Gateway Medical Center
🇺🇸Gilbert, Arizona, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
University of Arkansas for Medical Sciences - Winthrop P. Rockefeller Cancer Institute
🇺🇸Little Rock, Arkansas, United States
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
Cedars Sinai Medical Center Oncology IDS Pharmacy Attn:Suwicha Limvorasak ,PharmaD
🇺🇸Los Angeles, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute (SOCCI)
🇺🇸Los Angeles, California, United States
Sylvester Comprehensive Cancer Center - The Lennar Foundation Medical Center
🇺🇸Coral Gables, Florida, United States
Sylvester Comprehensive Cancer Center- Deerfield Beach
🇺🇸Deerfield Beach, Florida, United States
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
UHealth Tower
🇺🇸Miami, Florida, United States
UChicago Medicine - River East
🇺🇸Chicago, Illinois, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
UChicago Medicine at Ingalls - Flossmoor
🇺🇸Flossmoor, Illinois, United States
UChicago Medicine Ingalls Memorial
🇺🇸Harvey, Illinois, United States
University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
🇺🇸New Lenox, Illinois, United States
The University of Chicago Medicine Center for Advanced Care Orland Park
🇺🇸Orland Park, Illinois, United States
UChicago Medicine at Ingalls - Tinley Park
🇺🇸Tinley Park, Illinois, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
The University of Kansas Cancer Center ,Investigational Drug Services
🇺🇸Fairway, Kansas, United States
The University of Kansas Clinical Research Center
🇺🇸Fairway, Kansas, United States
The University of Kansas Hospital Investigational Drug Services
🇺🇸Kansas City, Kansas, United States
The University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
The University of Kansas Medical Center Medical Office Building
🇺🇸Kansas City, Kansas, United States
University of Kansas Hospital Cambridge North Tower A
🇺🇸Kansas City, Kansas, United States
The University of Kansas Cancer Center - Indian Creek Campus
🇺🇸Overland Park, Kansas, United States
The University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
OIDS, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Also Imaging Facility)
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Nebraska Medicine - Bellevue Medical Center
🇺🇸Bellevue, Nebraska, United States
Nebraska Medicine - Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Nebraska Medicine - Cancer Center at Village Pointe Health Center
🇺🇸Omaha, Nebraska, United States
University Of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Arthur J.E. Child Comprehensive Cancer Centre
🇨🇦Calgary, Alberta, Canada
Tom Baker Cancer Center
🇨🇦Calgary, Alberta, Canada
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada