Study of ACTR087 in Combination With SEA-BCMA in Subjects With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This is a phase 1, multi-center, single-arm, open-label study evaluating the safety, tolerability, and anti-myeloma activity of ACTR087 (an autologous T cell product) in combination with SEA-BCMA (a monoclonal antibody) in subjects with relapsed or refractory Multiple Myeloma.

Official Title
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A Phase 1 Study of ACTR087, an Autologous T Cell Product, in Combination With SEA-BCMA, a Monoclonal Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma, Multiple Myeloma in Relapse, Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: ACTR087
* Biological: SEA-BCMA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent obtained prior to study procedures Histologically- or cytologically-confirmed relapsed or refractory multiple myeloma (MM) with measurable disease Must have received at least 3 prior lines of therapy to include treatment with a proteasome inhibitor (eg, bortezomib, carfilzomib, or ixazomib) and an immunomodulatory agent (eg, lenalidomide, pomalidomide) unless double-refractory to both; and a hematopoietic stem cell transplant (HSCT), for those subjects considered HSCT-eligible. Quantitative serum IgG levels for subjects with IgG MM must not exceed the institutional upper limit of normal (ULN) ECOG 0 or 1 Life expectancy of at least 6 months Absolute neutrophil (ANC) count greater than 1000/ µL Platelet count greater than 50,000/µL Estimated GFR >30mL/min/1.73m2 Exclusion Criteria: Known active central nervous system (CNS) involvement by MM Systemic rheumatic or autoimmune diseases or acute or chronic infections Uncontrolled thromboembolic events or recent severe hemorrhage Subjects who are currently using more than 5mg/day of prednisone (or an equivalent glucocorticoid exceeding physiologic replacement levels) Prior treatment as follows: T cell-directed antibody therapy (eg. Alemtuzumab, anti-thymocyte globulin) within 6 months of enrollment Any prior myeloma-directed therapy including cytotoxic chemotherapy, biologic therapy, or radiotherapy within 2 weeks of enrollment Any mAb or other protein therapeutic containing Fc-domains within 4 weeks of enrollment Experimental agents within 3 half-lives prior to enrollment, unless progression is documented on therapy Prior BCMA-directed investigational agents at any time Prior cell or gene therapy, excluding transfers of genetically unmodified autologous cells (eg. Hematopoietic stem cell transplantation), at any time; or prior allogeneic HSCT at any time Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACTR087 in combination with SEA-BCMA<br> | Biological: ACTR087<br>* Autologous T cell product<br>Biological: SEA-BCMA<br>* B-cell maturation antigen (BCMA)-directed antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of ACTR087 in combination with SEA-BCMA | Composite outcome measure assessed by committee review of dose limiting toxicities (DLTs), incidence and severity of AEs and clinically significant abnormalities of laboratory values | 28 days | 
| Determination of recommended Phase 2 dosing regimen | Review of DLTs, Maximum tolerated contour (MTC), incidence and severity of AEs and clinically significant abnormalities of laboratory values | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of SEA-BCMA as measured by incidence of Treatment Emergent Adverse Events (TEAEs) | Review of all TEAEs, including incidence and severity of AEs, DLTs and clinically significant abnormalities of laboratory values | 21 days | 
| Anti-myeloma activity as measured by overall response rate (per IMWG response criteria) |  | 52 weeks | 
| Anti-myeloma activity as measured by duration of response |  | 52 weeks | 
| Anti-myeloma activity as measured by progression-free survival |  | 52 weeks | 
| Anti-myeloma activity as measured by overall survival |  | 52 weeks | 
| Assessment of persistence of ACTR087 as measured by flow cytometry and qPCR |  | 52 weeks | 
| Assessment of ACTR087 phenotype and function as measured by flow cytometry |  | 52 weeks | 
| Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR087 administration | Levels of inflammatory markers, cytokines/chemokines | 52 weeks | 
| SEA-BCMA PK | SEA-BCMA plasma concentration | 52 weeks | 
| Assessment of anti-drug antibodies (ADA) after SEA-BCMA administration | Incidence of ADAs to SEA-BCMA | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adoptive T cells, BCMA, SEA-BCMA, B Cell Maturation Antigen, ACTR, ACTR087, T cell, T cell product, relapsed, refractory, multiple myeloma, autologous, gene therapy, cell therapy