MagnetisMM-9: A Study to Learn About the Study Medicine (Elranatamab) in Participants With Multiple Myeloma That Has Come Back After Responding to Treatment or Has Not Responded to Treatment

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05014412

Collaborator

(none)

Enrollment

Locations

Arms

41.9

Anticipated Duration (Months)

2.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety of a step-up dosing approach (starting with low doses followed by higher doses) of the study medicine (elranatamab) in participants with multiple myeloma that has come back after responding to treatment or has not responded to treatment (relapsed/refractory multiple myeloma). This study will also look at the safety and efficacy of different doses of elranatamab, as well as different intervals between doses.

Participants in the study will receive elranatamab as an injection under the skin at the study clinic. After the initial step-up doses, participants will start receiving one dose every week. The frequency of clinic visits for injections may then decrease over time. Participation will be at least two years.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Elranatamab	Phase 2

Detailed Description

The purpose of this study is to evaluate the safety (in particular the rate of Grade ≥ 2 CRS) of a step-up priming dose regimen of elranatamab in participants with relapsed/refractory multiple myeloma. In addition, this study will assess the safety of different dosing regimens of elranatamab and if it can provide a clinical benefit in those participants. Elranatamab is a bispecific antibody: binding of elranatamab to CD3-expressing T-cells and BCMA-expressing multiple myeloma cells causes targeted T-cell-mediated cytotoxicity.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

76 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A PHASE 1/2, OPEN-LABEL, MULTICENTER STUDY TO EVALUATE A DOSING REGIMEN WITH TWO STEP-UP PRIMING DOSES AND LONGER DOSING INTERVALS OF ELRANATAMAB (PF-06863135) MONOTHERAPY IN PARTICIPANTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA

Actual Study Start Date :

Oct 7, 2021

Anticipated Primary Completion Date :

Jun 27, 2023

Anticipated Study Completion Date :

Apr 3, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 Evaluation of step-up priming dosing	Drug: Elranatamab BCMA-CD3 bispecific antibody
Experimental: Part 2A Dose determination	Drug: Elranatamab BCMA-CD3 bispecific antibody
Experimental: Part 2B Dose expansion	Drug: Elranatamab BCMA-CD3 bispecific antibody
Experimental: Part 2C To explore higher dose intensity	Drug: Elranatamab BCMA-CD3 bispecific antibody

Outcome Measures

Primary Outcome Measures

Proportion of participants with Grade 2 or higher Cytokine Release Syndrome (CRS) [Cycle 1 (28 days)]
Cytokine release syndrome severity assessed by American Society for Transplantation and Cellular Therapy (ASTCT) criteria

Secondary Outcome Measures

Incidence of Dose Limiting Toxicities (Part 2A only) [Cycle 2 (28 days)]
Frequency of Adverse Events [Up to 90 days after last dose and for approximately 2 years]
Adverse Events as characterized by type, frequency, severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5, timing, seriousness, and relationship to elranatamab
Frequency of laboratory abnormalities [Assessed at every cycles [each cycle approximately 28 days]]
Objective response rate [Assessed approximately every 28 days and for approximately 2 years]
Objective response rate per International Myeloma Working Group (IMWG) response criteria
Cumulative Complete Response Rate [Assessed approximately every 28 days and for approximately 2 years]
Cumulative Complete Response Rate per IMWG response criteria
Time to response [Assessed approximately every 28 days and for approximately 2 years]
Time to response per IMWG response criteria
Duration of response [Assessed approximately every 28 days and for approximately 2 years]
Duration of response per IMWG response criteria
Duration of cumulative complete response rate [Assessed approximately every 28 days and for approximately 2 years]
Duration of cumulative complete response rate per IMWG response criteria
Progression Free Survival [Assessed approximately every 28 days for approximately 2 years]
Overall Survival [Approximately 2 years]
Minimal Residual Disease negativity rate [Assessed approximately every 12 months and for approximately 2 years]
Minimal Residual Disease negativity rate assessed by central lab per IMWG sequencing criteria
Pre- and postdose concentrations of elranatamab [Assessed approximately every 1 to 3 cycles [cycle of approximately 28 days]]
Pharmacokinetic of elranatamab
Incidence and titers of Anti-Drug Antibody and Neutralizing Antibody against elranatamab [Assessed approximately every 1 to 6 cycles [cycle of approximately 28 days]]
Immunogenicity of elranatamab

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of multiple myeloma (IMWG criteria, Rajkumar et al, 2014)
Measurable disease, as defined by at least 1 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

Refractory to at least one IMiD
Refractory to at least one PI
Refractory to at least one anti-CD38 antibody
Relapsed/refractory to last anti-myeloma regimen
ECOG performance status ≤1
Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1
Not pregnant and willing to use contraception

Exclusion Criteria:

Smoldering multiple myeloma
Active Plasma cell leukemia
POEMS syndrome
Amyloidosis
Stem cell transplant within 12 weeks prior to enrollment or active GVHD
Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection
Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
Previous treatment with an anti-BCMA bispecific antibody.
Live attenuated vaccine within 4 weeks of the first dose
Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
2	Cancer Care & Hematology - Fort Collins	Fort Collins	Colorado	United States	80528
3	UCHealth Cancer Care & Hematology - Greeley	Greeley	Colorado	United States	80634
4	UCHealth Cancer Care & Hematology - Loveland	Loveland	Colorado	United States	80538
5	UF Health Shands Cancer Hospital	Gainesville	Florida	United States	32608
6	UF Health Shands Hospital	Gainesville	Florida	United States	32610
7	Pikeville Medical Center, INC	Pikeville	Kentucky	United States	41501
8	Tulane Cancer Center	New Orleans	Louisiana	United States	70112
9	Tulane Medical Center	New Orleans	Louisiana	United States	70112
10	Tufts Medical Center	Boston	Massachusetts	United States	02111
11	University of Michigan	Ann Arbor	Michigan	United States	48109
12	Henry Ford Hospital	Detroit	Michigan	United States	48202
13	Cleveland Clinic Taussig Cancer Institute	Cleveland	Ohio	United States	44195
14	Fox Chase Cancer Center Anatomic Pathology	Philadelphia	Pennsylvania	United States	19111
15	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
16	Jeanes Hospital Department of Pathology	Philadelphia	Pennsylvania	United States	19111
17	St. David's South Austin Medical Center	Austin	Texas	United States	78704
18	Blood Cancer and Stem Cell Transplant Clinic	San Antonio	Texas	United States	78229
19	Methodist Healthcare System of San Antonio dba Methodist Hospital	San Antonio	Texas	United States	78229
20	Huntsman Cancer Institute, University of Utah	Salt Lake City	Utah	United States	84112
21	Nagoya City University Hospital	Nagoya	Aichi	Japan	467-8602
22	Kobe City Medical Center General Hospital	Kobe-city	Hyogo	Japan	650-0047
23	National Cancer Center Hospital	Chuo-ku	Tokyo	Japan	104-0045
24	Japanese Red Cross Medical Center	Shibuya-ku	Tokyo	Japan	150-8935
25	University Hospital,Kyoto Prefectural University of Medicine	Kyoto		Japan	602-8566
26	China Medical University Hospital	Taichung		Taiwan	40447
27	National Cheng Kung University Hospital	Tainan		Taiwan	704
28	Taipei Veterans General Hospital	Taipei City		Taiwan	11217
29	National Taiwan University Hospital	Taipei		Taiwan	10002
30	University Hospital Southampton NHS Foundation Trust	Southampton	Hampshire	United Kingdom	SO16 6YD
31	The Royal Marsden NHS Foundation Trust	Sutton	Surrey	United Kingdom	SM2 5PT
32	Guy's and St Thomas' NHS Foundation Trust	London		United Kingdom	SE1 9RT
33	King's College Hospital NHS Foundation Trust	London		United Kingdom	SE5 9RS
34	University College London Hospitals NHS Foundation Trust NIHR	London		United Kingdom	W1T 7HA