MagnetisMM-4: Umbrella Study of Elranatamab (PF-06863135) in Combination With Anti-Cancer Treatments in Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to determine the Recommended Phase 2 Dose and clinical benefit of elranatamab in combination with other anti-cancer therapies in participants with multiple myeloma.

Official Title
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A PHASE 1B/2, OPEN LABEL UMBRELLA STUDY OF ELRANATAMAB (PF-06863135), A B-CELL MATURATION ANTIGEN (BCMA) CD3 BISPECIFIC ANTIBODY, IN COMBINATION WITH OTHER ANTI-CANCER TREATMENTS IN PARTICIPANTS WITH MULTIPLE MYELOMA

Conditions
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Multiple Myeloma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed/refractory multiple myeloma with at least 3 prior lines of therapy Refractory to at least one IMiD, one proteasome inhibitor, and one anti-CD38 antibody Measurable disease defined by at least one 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 ECOG performance status 0 -1 Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade </= 1 Exclusion Criteria: Active plasma cell leukemia Amyloidosis Stem cell transplant with 12 weeks prior to enrollment, or active GVHD POEMS syndrome Any active uncontrolled bacterial, fungal, or viral infection Impaired cardiovascular function or clinically significant cardiovascular diseases within 6 months prior to enrollment Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of study treatment (whichever is longer) Sub-Study A Only: Previous treatment with BCMA bispecific antibody Sub-Study B Only: Previous treatment with BCMA directed therapy

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: Sub-Study A<br>BCMA-CD3 bispecific antibody + gamma secretase inhibitor | Drug: Elranatamab + Nirogacestat<br>* BCMA-CD3 bispecific antibody + gamma secretase inhibitor<br>* Other names: PF-06863135;|
| Experimental: Sub-Study B<br>BCMA-CD3 bispecific antibody + immunomodulatory drug | Drug: Elranatamab + lenalidomide + dexamethasone<br>* BCMA-CD3 bispecific antibody + immunomodulatory<br>* Other names: PF-06863135; Revlimid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sub-Study A Phase 1: Dose Limiting Toxicity | Number of participants with Dose Limiting Toxicity | 35 days | 
| Sub-Study A Phase 2: Objective Response Rate | Objective response rate (IMWG response criteria) | assessed every 4 weeks (for approximately 2 years) | 
| Sub-Study B Phase 1 Escalation: Dose Limiting Toxicity | Number of participants with Dose Limiting Toxicity | 42 days | 
| Sub-Study B Phase 1 Expansion: Frequency of Treatment-Emergent Adverse Events | Type and severity per NCI CTCAE v5 (CRS and ICANS assessed per ASTCT criteria) | assessed for approximately 2 years | 
| Sub-Study B Phase 1 Expansion: Frequency of Laboratory Abnormalities | Type and severity per NCI CTCAE v5 | assessed every cycle (each cycle approximately 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sub-Study A Phase 1: Objective Response Rate | Objective response rate (IMWG response criteria) | assessed every 4 weeks (for approximately 2 years) | 
| Sub-Study A Phase 1 and Phase 2: Complete Response Rate | Complete response rate (IMWG response criteria) | assessed every 4 weeks (for approximately 2 years) | 
| Sub-Study A Phase 1 and Phase 2: Time to Response | Time to response (IMWG criteria) | assessed every 4 weeks (for approximately 2 years) | 
| Sub-Study A Phase 1 and 2: Duration of Response | Duration of response (IMWG response criteria) | assessed every 4 weeks (for approximately 2 years) | 
| Sub-Study A Phase 1 and Phase 2: Duration of Complete Response | Duration of complete response (IMWG response criteria) | assessed every 4 weeks (for approximately 2 years) | 
| Sub-Study A Phase 1 and Phase 2: Progression Free Survival | Progression free survival (IMWG response criteria) | assessed every 4 weeks (for approximately 2 years) | 
| Sub-Study A Phase 1 and Phase 2: Overall Survival | Overall survival | assessed for approximately 2 years | 
| Sub-Study A Phase 1 and Phase 2: Minimal Residual Disease Negativity Rate | Minimal residual disease negativity rate (IMWG response criteria) | assessed approximately every 12 months (for approximately 2 years) | 
| Sub-Study A Phase 1 and Phase 2: Frequency of Treatment-Emergent Adverse Events | Type and severity per NCI CTCAE v5 (CRS and ICANS assessed per ASTCT criteria) | assessed for approximately 2 years | 
| Sub-Study A Phase 1 and Phase 2: Frequency of Laboratory Abnormalities | Type and severity per NCI CTCAE v5 | assessed every cycle (each cycle approximately 28 days) | 
| Sub-Study A Phase 1 and Phase 2: Immunogenicity of elranatamab in combination with nirogacestat | Anti-drug antibodies and neutralizing antibodies against elranatamab | assessed approximately every 1 to 3 cycles (each cycle approximately 28 days) | 
| Sub-Study A Phase 1 and Phase 2: Concentrations of elranatamab and/or nirogacestat | Pre-dose and post-dose concentrations of elranatamab; pre-dose concentrations of nirogacestat | assessed approximately every 1 to 3 cycles (each cycle approximately 28 days) | 
| Sub-Study A Phase 1: Maximum Observed Concentration (Cmax) for elranatamab | Cmax for elranatamab administration | assessed after first elranatamab dose (approximately 3-7 days) | 
| Sub-Study A Phase 1: Time to Maximum Concentration (Tmax) for elranatamab | Tmax for elranatamab administration | assessed after first elranatamab dose (approximately 3-7 days) | 
| Sub-Study A Phase 1: Area Under the Concentration versus Time Curve from Time 0 to the Last Measurable Concentration (AUClast) for elranatamab | AUClast for elranatamab administration | assessed after first elranatamab dose (approximately 3-7 days) | 
| Sub-Study B Phase 1 Escalation: Frequency of Treatment-Emergent Adverse Events | Type and severity per NCI CTCAE v5 (CRS and ICANS assessed per ASTCT criteria) | assessed for approximately 2 years | 
| Sub-Study B Phase 1 Escalation: Frequency of Laboratory Abnormalities | Type and severity per NCI CTCAE v5 | assessed every cycle (each cycle approximately 28 days) | 
| Sub-Study B Phase 1 Escalation and Expansion: Objective Response Rate | Objective response rate (IMWG response criteria) | assessed every 4 weeks (for approximately 2 years) | 
| Sub-Study B Phase 1 Escalation and Expansion: Complete Response Rate | Complete response rate (IMWG response criteria) | assessed every 4 weeks (for approximately 2 years) | 
| Sub-Study B Phase 1 Escalation and Expansion: Time to Response | Time to response (IMWG criteria) | assessed every 4 weeks (for approximately 2 years) | 
| Sub-Study B Phase 1 Escalation and Expansion: Duration of Response | Duration of response (IMWG response criteria) | assessed every 4 weeks (for approximately 2 years) | 
| Sub-Study B Phase 1 Escalation and Expansion: Duration of Complete Response | Duration of complete response (IMWG response criteria) | assessed every 4 weeks (for approximately 2 years) | 
| Sub-Study B Phase 1 Escalation and Expansion: Progression Free Survival | Progression free survival (IMWG response criteria) | assessed every 4 weeks (for approximately 2 years) | 
| Sub-Study B Phase 1 Escalation and Expansion: Overall Survival | Overall survival | assessed for approximately 2 years | 
| Sub-Study B Phase 1 Escalation and Expansion: Minimal Residual Disease Negativity Rate | Minimal residual disease negativity ratio (IMWG response criteria) | assessed approximately every 12 months (for approximately 2 years) | 
| Sub-Study B Phase 1 Escalation and Expansion: Immunogenicity of elranatamab in combination with lenalidomide | Anti-drug antibodies and neutralizing antibodies against elranatamab | assessed approximately every 1 to 3 cycles (each cycle approximately 28 days) | 
| Sub-Study B Phase 1 Escalation and Expansion: Concentrations of elranatamab and/or lenalidomide | Pre-dose and post-dose concentrations of elranatamab, pre-dose concentrations of lenalidomide | assessed approximately every 1 to 3 cycles (each cycle approximately 28 days) | 
| Sub-Study B Phase 1 Escalation and Expansion: Maximum Observed Concentrations (Cmax) for elranatamab | Cmax for elranatamab administration | assessed after first elranatamab dose (approximately 3-7 days) | 
| Sub-Study B Phase 1 Escalation and Expansion: Time to Maximum Concentration (Tmax) for elranatamab | Tmax for elranatamab administration | assessed after first elranatamab dose (approximately 3-7 days) | 
| Sub-Study B Phase 1 Escalation and Expansion: Area Under the Concentration versus Time Curve from Time 0 to the Last Measurable Concentration (AUClast) for elranatamab | AUClast for elranatamab administration | assessed after first elranatamab dose (approximately 3-7 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PF-06863135, Multiple Myeloma, BCMA, elranatamab, bispecific antibody, MagnetisMM-4