PF-06863135 As Single Agent And In Combination With Immunomodulatory Agents In Relapse/Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03269136
• Other study ID #: C1071001
• Secondary ID: 2019-000822-24
• Status: Completed
• Phase: Phase 1
• Start date: November 29, 2017
• Est. completion date: January 19, 2024

Study information

• Verified date: February 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: January 19, 2024
• Est. primary completion date: January 19, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• PF-06863135 monotherapy IV or SC
PF-06863135 will be administered intravenously or subcutaneously.
• PF-06863135 + dexamethasone
PF-06863135 will be administered intravenously or subcutaneously and dexamethasone orally.
• PF-06863135 + lenalidomide
PF-06863135 will be administered intravenously or subcutaneously and lenalidomide orally
• PF-06863135 + pomalidomide
PF-06863135 will be administered intravenously or subcutaneously and pomalidomide orally

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Unit 57, Special Services Building	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	McGill University Health center	Montreal	Quebec
Canada	MUHC, GLEN site	Montreal	Quebec
Canada	University Health Network - Princess Margaret Cancer Centre	Toronto	Ontario
United States	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Memorial Sloan Kettering Cancer Center at Basking Ridge	Basking Ridge	New Jersey
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The University of Chicago Medical Center, CCD - Investigational Drug Service Pharmacy	Chicago	Illinois
United States	UChicago Medicine - River East	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Memorial Sloan Kettering Cancer Center at Commack	Commack	New York
United States	Baylor University Medical Center	Dallas	Texas
United States	Investigational Drug Services, Baylor University Medical Center	Dallas	Texas
United States	Duke Cancer Center	Durham	North Carolina
United States	Duke University Health System: Adult Bone Marrow Transplant Clinic	Durham	North Carolina
United States	Duke University Hospital	Durham	North Carolina
United States	UCSD Medical Center - Encinitas	Encinitas	California
United States	UChicago Medicine at Ingalls - Flossmoor	Flossmoor	Illinois
United States	Memorial Sloan Kettering Cancer Center at Westchester	Harrison	New York
United States	UChicago Medicine Ingalls Memorial	Harvey	Illinois
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Hospital)	La Jolla	California
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Memorial Sloan Kettering Cancer Center at Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Cancer Center at Bergen	Montvale	New Jersey
United States	Henry Joyce Cancer Center	Nashville	Tennessee
United States	University of Chicago Comprehensive Cancer Center at Silver Cross Hospital	New Lenox	Illinois
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care	New York	New York
United States	The University of Chicago Medicine Center for Advanced Care Orland Park	Orland Park	Illinois
United States	UC San Diego Medical Center - Hillcrest	San Diego	California
United States	UChicago Medicine at Ingalls - Tinley Park	Tinley Park	Illinois
United States	Memorial Sloan Kettering Cancer Center at Nassau	Uniondale	New York
United States	UCSD Medical Center - Vista	Vista	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation: Number of participants with Dose-limiting toxicities (DLT)	Number of participants with DLTs	At the end of Cycle 1 (each Cycle is 21 or 28 days)
Primary	To evaluate anti-myeloma activity by objective response rate (ORR) in dose expansion	Percentage of participants with Objective Response Rate (ORR) using the international myeloma working group (IMWG) response criteria for multiple myeloma	From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)
Primary	To evaluate anti-myeloma activity by duration of response (DOR) in dose expansion	Time from first assessment of partial response or better to last assessment of partial response or better by IMWG criteria	From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)
Secondary	To evaluate incidence of treatment emergent adverse events and laboratory abnormalities	Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any laboratory abnormalities	From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)
Secondary	To evaluate anti-myeloma activity by objective response rate (ORR) in dose escalation	Percentage of participants with Objective Response Rate (ORR) using the international myeloma working group (IMWG) response criteria for multiple myeloma	From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)
Secondary	To evaluate anti-myeloma activity by time to event endpoints	Time from start date to date of first documentation of event (response or progression by IMWG criteria or death)	From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)
Secondary	To evaluate anti-myeloma activity by duration of event endpoints	Time from first assessment of event endpoint (response or stable disease) to last assessment of (response or stable disease) by IMWG criteria	From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)
Secondary	Impact of treatment on systemic soluble immune factors	Pre and post dose quantification of soluble cytokines in serum.	9 months on treatment
Secondary	Maximum plasma concentration (Cmax) of PF-06863135	Peak concentration of PF-06863135 during first cycle	Cycle 1 Day 1 and Cycle 2 Day 1 (3 to 4 weeks)
Secondary	Trough serum concentrations of PF-06863135 and dexamethasone	Trough serum concentrations of PF-06863135 and dexamethasone at selected cycles	From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)
Secondary	Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-06863135	AUC of PF-06863135 will be calculated at selected cycles	From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)
Secondary	Incidence and titers of anti-drug antibodies and neutralizing antibodies against PF-06863135	Number of participants with the presence of anti-PF-06863135 antibodies	From baseline and scheduled timepoints post dose through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)

External Links

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