Multiple Myeloma, Multiple Myeloma in Relapse, Refractory Multiple Myeloma
Conditions
Keywords
BCMA, SEA-BCMA, B Cell Maturation Antigen, ACTR, ACTR087, T cell, T cell product, relapsed, refractory, multiple myeloma, adoptive T cells, autologous, gene therapy, cell therapy
Brief summary
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.
Interventions
Sponsors
Seagen Inc.
Cogent Biosciences, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of ACTR087 in combination with SEA-BCMA | 28 days | Composite outcome measure assessed by committee review of dose limiting toxicities (DLTs), incidence and severity of AEs and clinically significant abnormalities of laboratory values |
| Determination of recommended Phase 2 dosing regimen | 52 weeks | Review of DLTs, Maximum tolerated contour (MTC), incidence and severity of AEs and clinically significant abnormalities of laboratory values |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of SEA-BCMA as measured by incidence of Treatment Emergent Adverse Events (TEAEs) | 21 days | Review of all TEAEs, including incidence and severity of AEs, DLTs and clinically significant abnormalities of laboratory values |
| 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 | 52 weeks | Levels of inflammatory markers, cytokines/chemokines |
| SEA-BCMA PK | 52 weeks | SEA-BCMA plasma concentration |
| Assessment of anti-drug antibodies (ADA) after SEA-BCMA administration | 52 weeks | Incidence of ADAs to SEA-BCMA |
Countries
United States
Outcome results
None listed