A Study to Learn About the Study Medicine (Elranatamab) Either Alone or in Combination With Dexamethasone in Participants With Multiple Myeloma That Has Come Back After Responding to Treatment or Has Not Responded to Treatment

Study Overview
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Brief Summary
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The purpose of Part 1 and Part 2 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). The purpose of Part 3 of the study is to evaluate the safety and efficacy of elranatamab in combination with dexamethasone during the first 6 cycles followed by elranatamab monotherapy. 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.

Detailed Description
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The purpose of Part 1 and Part 2 of the 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. The purpose of Part 3 is to evaluate the safety and efficacy of elranatamab in combination with dexamethasone during the first 6 cycles followed by elranatamab monotherapy. 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.

Official Title
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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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Elranatamab
* Drug: Elranatamab+ dexamethasone


Participation Criteria
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Eligibility Criteria
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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 Waldenström's macroglobulinemia Known active CNS involvement or clinical signs of myelomatous meningeal involvement 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 or Stage 0/1 malignancy with minimal risk of recurrence per investigator. Previous treatment with an anti-BCMA bispecific antibody or CAR-T cell therapy. 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) Known or suspected hypersensitivity to the study intervention, or any of its excipients or unable to tolerate systemic corticosteroids at doses planned to be administered in the study Part 3

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>Evaluation of step-up priming dosing | Drug: Elranatamab<br>* BCMA-CD3 bispecific antibody<br>|
| Experimental: Part 2A<br>Dose determination | Drug: Elranatamab<br>* BCMA-CD3 bispecific antibody<br>|
| Experimental: Part 2B<br>Dose expansion | Drug: Elranatamab<br>* BCMA-CD3 bispecific antibody<br>|
| Experimental: Part 2C<br>To explore higher dose intensity | Drug: Elranatamab<br>* BCMA-CD3 bispecific antibody<br>|
| Experimental: Part 3<br>To explore the combination with dexamethasone | Drug: Elranatamab+ dexamethasone<br>* BCMA-CD3 bispecific antibody + corticosteroids (dexamethasone)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with Grade 2 or higher Cytokine Release Syndrome (CRS) (Part 1 and 2) | Cytokine release syndrome severity assessed by American Society for Transplantation and Cellular Therapy (ASTCT) criteria | Cycle 1 (28 days) | 
| Number of participants with overall response rate (ORR) per International Myeloma Working Group (IMWG) criteria (Part 3). | Treatment effect of elranatamab + dexamethasone on ORR per IMWG criteria. | From the date of first dose until the first documentation of progressive disease (PD), death or start of new anticancer therapy, whichever occurs first (timeframe: approximately 2 years). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose Limiting Toxicities (Part 2A and 2C) |  | 28 days starting on the first dose of 116 or 152 mg | 
| Frequency of Adverse Events | 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 | Up to 90 days after last dose and for approximately 2 years | 
| Frequency of laboratory abnormalities |  | Assessed at every cycles [each cycle approximately 28 days] | 
| Objective response rate | Objective response rate per International Myeloma Working Group (IMWG) response criteria | Assessed approximately every 28 days and for approximately 2 years | 
| Complete Response Rate | Complete Response Rate per IMWG response criteria | Assessed approximately every 28 days and for approximately 2 years | 
| Time to response | Time to response per IMWG response criteria | Assessed approximately every 28 days and for approximately 2 years | 
| Duration of response | Duration of response per IMWG response criteria | Assessed approximately every 28 days and for approximately 2 years | 
| Duration of complete response rate | Duration of complete response rate per IMWG response criteria | Assessed approximately every 28 days and for approximately 2 years | 
| Progression Free Survival |  | Assessed approximately every 28 days for approximately 2 years | 
| Overall Survival |  | Approximately 2 years | 
| Minimal Residual Disease negativity rate | Minimal Residual Disease negativity rate assessed by central lab per IMWG sequencing criteria | Assessed approximately every 12 months and for approximately 2 years | 
| Pre- and postdose concentrations of elranatamab | Pharmacokinetic of elranatamab | Assessed approximately every 1 to 3 cycles [cycle of approximately 28 days] | 
| Incidence and titers of Anti-Drug Antibody and Neutralizing Antibody against elranatamab | Immunogenicity of elranatamab | Assessed approximately every 1 to 6 cycles [cycle of approximately 28 days] | 
| Proportion of participants with Grade 2 or higher Cytokine Release Syndrome (CRS) (Part 3) | Proportion of participants with Grade 2 or higher Cytokine Release Syndrome (CRS) when elranatamab is administered in combination with dexamethasone (Part 3) | Cycle 1 (28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCMA, Multiple Myeloma, Relapse/Refractory, RRMM, Elranatamab, Dexamethasone, Targeted T-cell, MagnetisMM, MM9, Phase 2, B-Cell Maturation Antigen, monoclonal antibody