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

Sponsor

Pfizer (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03269136

Collaborator

(none)

103

Enrollment

Locations

Arms

64.9

Anticipated Duration (Months)

2.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: PF-06863135 monotherapy IV or SC Drug: PF-06863135 + dexamethasone Drug: PF-06863135 + lenalidomide Drug: PF-06863135 + pomalidomide	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

103 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Nov 29, 2017

Anticipated Primary Completion Date :

Apr 28, 2023

Anticipated Study Completion Date :

Apr 28, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PF-06863135 BCMA-CD3 bispecific antibody	Drug: PF-06863135 monotherapy IV or SC PF-06863135 will be administered intravenously or subcutaneously. Other Names: BCMA-CD3 bispecific antibody
Experimental: PF-06863135 + dexamethasone BCMA-CD3 bispecific antibody + dexamethasone	Drug: PF-06863135 + dexamethasone PF-06863135 will be administered intravenously or subcutaneously and dexamethasone orally. Other Names: BCMA-CD3 bispecific antibody + dexamethasone
Experimental: PF-06863135 + lenalidomide BCMA-CD3 bispecific antibody + lenalidomide	Drug: PF-06863135 + lenalidomide PF-06863135 will be administered intravenously or subcutaneously and lenalidomide orally Other Names: BCMA-CD3 bispecific antibody + lenalidomide
Experimental: PF-06863135 + pomalidomide BCMA-CD3 bispecific antibody + pomalidomide	Drug: PF-06863135 + pomalidomide PF-06863135 will be administered intravenously or subcutaneously and pomalidomide orally Other Names: BCMA-CD3 bispecific antibody + pomalidomide

Outcome Measures

Primary Outcome Measures

Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) [At the end of Cycle 1 (each Cycle is 21 or 28 days)]
Number of participants with DLTs
To evaluate anti-myeloma activity by objective response rate (ORR) in dose expansion [From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)]
Percentage of participants with Objective Response Rate (ORR) using the international myeloma working group (IMWG) response criteria for multiple myeloma
To evaluate anti-myeloma activity by duration of response (DOR) in dose expansion [From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)]
Time from first assessment of partial response or better to last assessment of partial response or better by IMWG criteria

Secondary Outcome Measures

To evaluate incidence of treatment emergent adverse events and laboratory abnormalities [From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)]
Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any laboratory abnormalities
To evaluate anti-myeloma activity by objective response rate (ORR) in dose escalation [From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)]
Percentage of participants with Objective Response Rate (ORR) using the international myeloma working group (IMWG) response criteria for multiple myeloma
To evaluate anti-myeloma activity by time to event endpoints [From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)]
Time from start date to date of first documentation of event (response or progression by IMWG criteria or death)
To evaluate anti-myeloma activity by duration of event endpoints [From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)]
Time from first assessment of event endpoint (response or stable disease) to last assessment of (response or stable disease) by IMWG criteria
Impact of treatment on systemic soluble immune factors [9 months on treatment]
Pre and post dose quantification of soluble cytokines in serum.
Maximum plasma concentration (Cmax) of PF-06863135 [Cycle 1 Day 1 and Cycle 2 Day 1 (3 to 4 weeks)]
Peak concentration of PF-06863135 during first cycle
Trough serum concentrations of PF-06863135 and dexamethasone [From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)]
Trough serum concentrations of PF-06863135 and dexamethasone at selected cycles
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 [From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)]
AUC of PF-06863135 will be calculated at selected cycles
Incidence and titers of anti-drug antibodies and neutralizing antibodies against PF-06863135 [From baseline and scheduled timepoints post dose through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years)]
Number of participants with the presence of anti-PF-06863135 antibodies

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSD Medical Center - Encinitas	Encinitas	California	United States	92024
2	UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Hospital)	La Jolla	California	United States	92037
3	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
4	UC San Diego Medical Center - Hillcrest	San Diego	California	United States	92103
5	UCSD Medical Center - Vista	Vista	California	United States	92081
6	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia	United States	30342
7	Northside Hospital	Atlanta	Georgia	United States	30342
8	UChicago Medicine - River East	Chicago	Illinois	United States	60611
9	The University of Chicago Medical Center, CCD - Investigational Drug Service Pharmacy	Chicago	Illinois	United States	60637
10	University of Chicago Medical Center	Chicago	Illinois	United States	60637
11	UChicago Medicine at Ingalls - Flossmoor	Flossmoor	Illinois	United States	60422
12	UChicago Medicine Ingalls Memorial	Harvey	Illinois	United States	60426
13	University of Chicago Comprehensive Cancer Center at Silver Cross Hospital	New Lenox	Illinois	United States	60451
14	The University of Chicago Medicine Center for Advanced Care Orland Park	Orland Park	Illinois	United States	60462
15	UChicago Medicine at Ingalls - Tinley Park	Tinley Park	Illinois	United States	60477
16	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
17	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
18	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
19	Memorial Sloan Kettering Cancer Center at Basking Ridge	Basking Ridge	New Jersey	United States	07920
20	Memorial Sloan Kettering Cancer Center at Monmouth	Middletown	New Jersey	United States	07748
21	Memorial Sloan Kettering Cancer Center at Bergen	Montvale	New Jersey	United States	07645
22	Memorial Sloan Kettering Cancer Center at Commack	Commack	New York	United States	11725
23	Memorial Sloan Kettering Cancer Center at Westchester	Harrison	New York	United States	10604
24	Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care	New York	New York	United States	10021
25	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
26	Memorial Sloan Kettering Cancer Center at Nassau	Uniondale	New York	United States	11553
27	Duke University Health System: Adult Bone Marrow Transplant Clinic	Durham	North Carolina	United States	27705
28	Duke Cancer Center	Durham	North Carolina	United States	27710
29	Duke University Hospital	Durham	North Carolina	United States	27710
30	Henry Joyce Cancer Center	Nashville	Tennessee	United States	37232
31	Baylor University Medical Center	Dallas	Texas	United States	75246
32	Investigational Drug Services, Baylor University Medical Center	Dallas	Texas	United States	75246
33	Unit 57, Special Services Building	Calgary	Alberta	Canada	T2N 2T9
34	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
35	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
36	University Health Network - Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G2M9
37	McGill University Health center	Montreal	Quebec	Canada	H4A 3J1
38	MUHC, GLEN site	Montreal	Quebec	Canada	H4A3J1