Clinical trial NCT05090566: MagnetisMM-4: Umbrella Study of Elranatamab (PF-06863135) in Combination With Anti-Cancer Treatments in Multiple Myeloma
Official title: A PHASE 1B/2, OPEN LABEL UMBRELLA STUDY OF ELRANATAMAB (PF-06863135), A B-CELL MATURATION ANTIGEN (BCMA) CD3 BISPECIFIC ANTIBODY, IN COMBINATION WITH OTHER ANTI-CANCER TREATMENTS IN PARTICIPANTS WITH MULTIPLE MYELOMA
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: PF-06863135, Multiple Myeloma, BCMA, elranatamab, bispecific antibody, MagnetisMM-4
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-10-25
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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:

  1. Serum M-protein \>/= 0.5 g/dL by SPEP
  2. Urinary M-protein excretion \>/= 200 mg/24 hours by UPEP
  3. 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Sub-Study A Phase 1: Dose Limiting Toxicity
timeFrame: approximately 35 days
measure: Sub-Study A Phase 2: Objective Response Rate
timeFrame: assessed every 4 weeks (for approximately 2 years)
measure: Sub-Study B Phase 1 Escalation: Dose Limiting Toxicity
timeFrame: approximately 42 days
Secondary outcomes:
measure: Sub-Study A Phase 1: Objective Response Rate
timeFrame: assessed every 4 weeks (for approximately 2 years)
measure: Sub-Study A Phase 1 and Phase 2: Complete Response Rate
timeFrame: assessed every 4 weeks (for approximately 2 years)
measure: Sub-Study A Phase 1 and Phase 2: Time to Response
timeFrame: assessed every 4 weeks (for approximately 2 years)
measure: Sub-Study A Phase 1 and 2: Duration of Response
timeFrame: assessed every 4 weeks (for approximately 2 years)
measure: Sub-Study A Phase 1 and Phase 2: Duration of Complete Response
timeFrame: assessed every 4 weeks (for approximately 2 years)
measure: Sub-Study A Phase 1 and Phase 2: Progression Free Survival
timeFrame: assessed every 4 weeks (for approximately 2 years)
measure: Sub-Study A Phase 1 and Phase 2: Overall Survival
timeFrame: assessed for approximately 2 years
measure: Sub-Study A Phase 1 and Phase 2: Minimal Residual Disease Negativity Rate
timeFrame: assessed approximately every 12 months (for approximately 2 years)
measure: Sub-Study A Phase 1 and Phase 2: Frequency of Treatment-Emergent Adverse Events
timeFrame: assessed for approximately 2 years
measure: Sub-Study A Phase 1 and Phase 2: Frequency of Laboratory Abnormalities
timeFrame: assessed every cycle (each cycle approximately 28 days)
measure: Sub-Study A Phase 1 and Phase 2: Immunogenicity of elranatamab in combination with nirogacestat
timeFrame: assessed approximately every 1 to 3 cycles (each cycle approximately 28 days)
measure: Sub-Study A Phase 1 and Phase 2: Concentrations of elranatamab and/or nirogacestat
timeFrame: assessed approximately every 1 to 3 cycles (each cycle approximately 28 days)
measure: Sub-Study A Phase 1: Maximum Observed Concentration (Cmax) for elranatamab
timeFrame: assessed after first elranatamab dose (approximately 3-7 days)
measure: Sub-Study A Phase 1: Time to Maximum Concentration (Tmax) for elranatamab
timeFrame: assessed after first elranatamab dose (approximately 3-7 days)
measure: Sub-Study A Phase 1: Area Under the Concentration versus Time Curve from Time 0 to the Last Measurable Concentration (AUClast) for elranatamab
timeFrame: assessed after first elranatamab dose (approximately 3-7 days)
measure: Sub-Study B Phase 1 Escalation: Frequency of Treatment-Emergent Adverse Events
timeFrame: assessed for approximately 2 years
measure: Sub-Study B Phase 1 Escalation: Frequency of Laboratory Abnormalities
timeFrame: assessed every cycle (each cycle approximately 28 days)
measure: Sub-Study B Phase 1 Escalation: Objective Response Rate
timeFrame: assessed every 4 weeks (for approximately 2 years)
measure: Sub-Study B Phase 1 Escalation: Complete Response Rate
timeFrame: assessed every 4 weeks (for approximately 2 years)
measure: Sub-Study B Phase 1 Escalation: Time to Response
timeFrame: assessed every 4 weeks (for approximately 2 years)
measure: Sub-Study B Phase 1 Escalation: Duration of Response
timeFrame: assessed every 4 weeks (for approximately 2 years)
measure: Sub-Study B Phase 1 Escalation: Duration of Complete Response
timeFrame: assessed every 4 weeks (for approximately 2 years)
measure: Sub-Study B Phase 1 Escalation: Progression Free Survival
timeFrame: assessed every 4 weeks (for approximately 2 years)
measure: Sub-Study B Phase 1 Escalation: Overall Survival
timeFrame: assessed for approximately 2 years
measure: Sub-Study B Phase 1 Escalation: Minimal Residual Disease Negativity Rate
timeFrame: assessed approximately every 12 months (for approximately 2 years)
measure: Sub-Study B Phase 1 Escalation: Immunogenicity of elranatamab in combination with lenalidomide
timeFrame: assessed approximately every 1 to 3 cycles (each cycle approximately 28 days)
measure: Sub-Study B Phase 1 Escalation: Concentrations of elranatamab and/or lenalidomide
timeFrame: assessed approximately every 1 to 3 cycles (each cycle approximately 28 days)
measure: Sub-Study B Phase 1 Escalation: Maximum Observed Concentrations (Cmax) for elranatamab
timeFrame: assessed after first elranatamab dose (approximately 3-7 days)
measure: Sub-Study B Phase 1 Escalation: Time to Maximum Concentration (Tmax) for elranatamab
timeFrame: assessed after first elranatamab dose (approximately 3-7 days)
measure: Sub-Study B Phase 1 Escalation: Area Under the Concentration versus Time Curve from Time 0 to the Last Measurable Concentration (AUClast) for elranatamab
timeFrame: assessed after first elranatamab dose (approximately 3-7 days)
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner Gateway Medical Center
state: Arizona
city: Gilbert
country: United States
facility: Banner Gateway Medical Pavilion
state: Arizona
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences - Winthrop P. Rockefeller Cancer Institute
state: Arkansas
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Encino
country: United States
facility: Clinical Research Advisors
state: California
city: Los Angeles
country: United States
facility: Clinical Research Advisors
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center Oncology IDS Pharmacy Attn:Suwicha Limvorasak ,PharmaD
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute (SOCCI)
state: California
city: Los Angeles
country: United States
facility: Clinical Research Advisors
state: California
city: Coral Gables
country: United States
facility: Sylvester Comprehensive Cancer Center - The Lennar Foundation Medical Center
state: Florida
city: Deerfield Beach
country: United States
facility: Sylvester Comprehensive Cancer Center- Deerfield Beach
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: UHealth Tower
state: Florida
city: Chicago
country: United States
facility: UChicago Medicine - River East
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Flossmoor
country: United States
facility: UChicago Medicine at Ingalls - Flossmoor
state: Illinois
city: Harvey
country: United States
facility: UChicago Medicine Ingalls Memorial
state: Illinois
city: New Lenox
country: United States
facility: University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
state: Illinois
city: Orland Park
country: United States
facility: The University of Chicago Medicine Center for Advanced Care Orland Park
state: Illinois
city: Tinley Park
country: United States
facility: UChicago Medicine at Ingalls - Tinley Park
state: Illinois
city: Baltimore
country: United States
facility: OIDS, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Also Imaging Facility)
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Calgary
country: Canada
facility: Arthur J.E. Child Comprehensive Cancer Centre
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: