Clinical trial NCT03269136: PF-06863135 As Single Agent And In Combination With Immunomodulatory Agents In Relapse/Refractory Multiple Myeloma
Official title: MAGNETISMM-1 A PHASE I, OPEN LABEL STUDY TO EVALUATE THE SAFETY, PHARMACOKINETIC, PHARMACODYNAMIC AND CLINICAL ACTIVITY OF ELRANATAMAB (PF-06863135), A B-CELL MATURATION ANTIGEN (BCMA) - CD3 BISPECIFIC ANTIBODY, AS A SINGLE AGENT AND IN COMBINATION WITH IMMUNOMODULATORY AGENTS IN PATIENTS WITH RELAPSED/REFRACTORY ADVANCED MULTIPLE MYELOMA (MM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
relapse/ refractory multiple myeloma
bispecific antibody
bispecific
BCMA
BCMA- CD3 bispecific
Phase 1
PF-06863135
dexamethasone
lenalidomide
pomalidomide
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-08-31
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: To assess the safety and tolerability at increasing dose levels of PF-06863135 in patients with relapse/ refractory multiple myeloma in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.

Detailed description: Study C1071001 is a Phase 1, open label, multi dose, multi center, dose escalation, safety, pharmacokinetic (PK) and pharmacodynamic study of PF-06863135 in adult patients with advanced multiple myeloma who have relapsed from or are refractory to standard therapy. This is a two part study; Part 1 will assess the safety and tolerability of increasing dose levels of PF-06863135 and Part 2 will evaluate safety and anti-myeloma activity of PF-06863135 at the RP2Ds determined in Part 1.

Eligibility criteria: Inclusion Criteria:

* Relapsed/refractory multiple myeloma
* Progressed or are intolerant of established therapies including proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody
* Performance Status of 0- 1 ( Performance Score 2 is permitted only if due to underlying myeloma)
* Adequate bone marrow, hematological, kidney and liver function
* Resolved acute effects of any prior therapy to baseline severity
* Not pregnant

Exclusion Criteria:

* Recent history of other malignancies
* History of active autoimmune disorders
* Any form of primary immunodeficiency
* Active and clinically significant bacterial, fungal, or viral infection
* Evidence of active mucosal or internal bleeding
* History of severe immune-mediated adverse event with prior immunomodulatory treatment
* Major surgery within 4 weeks of study treatment start
* Radiation therapy within 2 weeks of study treatment start
* History of stem cell transplant (autologous or allogeneic) within 100 days prior to study enrollment
* Donor Lymphocyte Infusion (DLI) within 30 days prior to study entry
* Less than 30 days since last dose of antibody based therapies or less than 5 half-lives since last dose of previous therapy
* Requirement for systemic immune suppressive medication except as permitted in the protocol
* Current requirement for chronic blood product support

Primary outcomes:
measure: Part 1: Number of Participants With Drug Limiting Toxicities (DLTs) Graded According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v)4.03
timeFrame: Cycle 1 (21 Days)
measure: Part 2: Objective Response Rate (ORR) as Per International Myeloma Working Group (IMWG) Criteria
timeFrame: From the first dose of study treatment until the first documented sCR or CR or PR or VGPR or new anti-cancer therapies or death, whichever occurred first (maximum up to 34.3 months)
measure: Part 2: Duration of Response (DOR) as Per IMWG Criteria
timeFrame: From the first documentation of objective tumor response to first documentation of objective tumor progression or new anti-cancer therapies or death, whichever occurred first, (maximum up to 34.3 months)
Secondary outcomes:
measure: Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs), Serious AEs, Treatment Related AEs, Grade 3 or 4 AEs and Grade 5 AEs as Graded by NCI CTCAE v4.03
timeFrame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 43.3 months)
measure: Part 1: Number of Participants With Shifts From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post-Baseline in Hematology Parameters
timeFrame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 43.3 months)
measure: Part 1: Number of Participants With Shifts From Grade <= 2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Chemistry Parameters
timeFrame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 43.3 months)
measure: Part 1: Number of Participants With Shifts From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Urinalysis
timeFrame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 43.3 months)
measure: Part 1: ORR as Per IMWG Criteria
timeFrame: From the first dose of study treatment until the first documented sCR or CR or PR or VGPR or new anti-cancer therapies or death, whichever occurred first (maximum up to 63.31 months)
measure: Part 1: Time to Response (TTR) as Per IMWG Criteria
timeFrame: From the first dose of study treatment until the first documented sCR or CR or PR or VGPR or new anti-cancer therapies or death, whichever occurred first (maximum up to 63.31 months)
measure: Part 1: Complete Response Rate (CRR) as Per IMWG Criteria
timeFrame: From the first dose of study treatment until the first documented sCR or CR or new anti-cancer therapies or death, whichever occurred first (maximum up to 63.31 months)
measure: Part 1: DOR as Per IMWG Criteria
timeFrame: From the first documentation of objective tumor response to first documentation of objective tumor progression or new anti-cancer therapies or death, whichever occurred first, (maximum up to 63.31 months)
measure: Part 1: Duration of Complete Response (DoCR) as Per IMWG Criteria
timeFrame: From the first documentation of complete response to the first documentation of tumor progression or death, whichever occurred first (maximum up to 63.31 months)
measure: Part 1: Duration of Stable Disease (DOSD) as Per IMWG Criteria
timeFrame: Time from the first documentation of objective stable disease to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first (maximum up to 63.31 months)
measure: Part 1: Progression Free Survival (PFS) as Per IMWG Criteria
timeFrame: From start date of study treatment to date of first documentation of progression or death due to any cause, whichever occurred first (maximum up to 63.31 months)
measure: Part 1: Overall Survival (OS)
timeFrame: Time from start date of study treatment to date of death due to any cause or last-known-alive date, whichever occurred first (maximum up to 63.31 months)
measure: Part 1: Percentage of Participants With Negative Minimal Residual Disease (MRD) Using IMWG MRD Criteria
timeFrame: Anytime from date of first dose until the first documentation of confirmed PD, death or start of new anticancer therapy, whichever occurred first (maximum up to 63.31 months)
measure: Part 1: Maximum Observed Concentration (Cmax) of PF-06863135
timeFrame: 0 hours (h) on Day 1 of Cycle (C) 0; 0, 2 and 4h on Day 1 of C1 and C2
measure: Part 1: Area Under the Concentration-Time Profile From Time 0 to End of Dosing Interval (AUCtau)
timeFrame: 0 hours (h) on Day 1 of Cycle (C) 0; 0, 2 and 4h on Day 1 of C1 and C2
measure: Part 1C and Part 1D: Plasma Concentration of Lenalidomide and Pomalidomide
timeFrame: Cycle 1 (0 hours post dose on Day 1, 8 and 15); Cycle 2 (0 hours on Day 15)
measure: Part 1: Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF-06863135
timeFrame: From first dose of the study treatment (Day 1) up to end of study treatment (maximum up to 63.31 months)
measure: Part 1: Concentration of Soluble Cytokines in Serum
timeFrame: Part 1: C1 (0, 2, 4 & 8 hours [h] post dose on Day [D] 1, 24h post dose on D2, 72h post dose on D3); Part 1.1, 1C & 1D: C0 (0, 2, 4 & 8h post dose on D1, 24h post dose on D2); C1 (0, 2, 4 & 8h post dose on D1, 24h post dose on D2, 72h post dose on D3)
measure: Part 2: Number of Participants With AEs, Serious AEs, Treatment Related AEs, Grade 3 or 4 AEs and Grade 5 AEs as Graded by NCI CTCAE v4.03
timeFrame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 32.3 months)
measure: Part 2: Number of Participants With Shifts From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Hematology Parameters
timeFrame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 32.3 months)
measure: Part 2: Number of Participants With Shifts From Grade <= 2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Chemistry Parameters
timeFrame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 32.3 months)
measure: Part 2: Number of Participants With Shifts From Grade <=2 to Grade 3 or 4 Post-Baseline in Urinalysis
timeFrame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 32.3 months)
measure: Part 2: CRR as Per IMWG Criteria
timeFrame: From the first dose of study treatment until the first documented sCR or CR or new anti-cancer therapies or death, whichever occurred first (maximum up to 34.3 months)
measure: Part 2: DoCR as Per IMWG Criteria
timeFrame: From the first documentation of complete response to the first documentation of tumor progression or death, whichever occurred first (maximum up to 34.3 months)
measure: Part 2: TTR as Per IMWG Criteria
timeFrame: From the first dose of study treatment until the first documented sCR or CR or PR or VGPR or new anti-cancer therapies or death, whichever occurred first (maximum up to 34.3 months)
measure: Part 2: DOSD as Per IMWG Criteria
timeFrame: Time from the first documentation of objective stable disease to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first (maximum up to 34.3 months)
measure: Part 2: PFS as Per IMWG Criteria
timeFrame: From start date of study treatment to date of first documentation of progression or death due to any cause, whichever occurred first (maximum up to 34.3 months)
measure: Part 2: OS
timeFrame: Time from start date of study treatment to date of death due to any cause or last-known-alive date, whichever occurred first (maximum up to 34.3 months)
measure: Part 2: Percentage of Participants With Negative MRD After Treatment With PF-06863135 Using IMWG MRD Criteria
timeFrame: Anytime from date of first dose until the first documentation of confirmed PD, death or start of new anticancer therapy whichever occurred first (maximum up to 34.3 months)
measure: Part 2: Number of Participants With ADA and NAb Against PF-06863135
timeFrame: From first dose of the study treatment (Day 1) up to end of study treatment (maximum up to 34.3 months)
measure: Part 2: Concentration of Soluble Cytokines in Serum
timeFrame: Cycle 0 (0, 2, 4 and 8 hours post dose on Day 1, 24 hours post dose on Day 2); Cycle 1 (0, 2, 4 and 8 hours post dose on Day 1, 24 hours post dose on Day 2, 72 hours post dose on Day 3)
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: UCSD Medical Center - Encinitas
state: California
city: La Jolla
country: United States
facility: UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Hospital)
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: San Diego
country: United States
facility: UC San Diego Medical Center - Hillcrest
state: California
city: Vista
country: United States
facility: UCSD Medical Center - Vista
state: California
city: Atlanta
country: United States
facility: Blood and Marrow Transplant Group of Georgia
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: UChicago Medicine - River East
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center, CCD - Investigational Drug Service Pharmacy
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: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center at Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Cancer Center at Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Cancer Center at Bergen
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center at Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center at Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Cancer Center at Nassau
state: New York
city: Durham
country: United States
facility: Duke University Health System: Adult Bone Marrow Transplant Clinic
state: North Carolina
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Nashville
country: United States
facility: Henry Joyce Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: Investigational Drug Services, Baylor University Medical Center
state: Texas
city: Calgary
country: Canada
facility: Unit 57, Special Services Building
state: Alberta
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: University Health Network - Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: MUHC, GLEN site
state: Quebec
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: