Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I
Hematology Disease Topics & Pathways:
Biological, multiple myeloma, Diseases, Adult, Therapies, bioengineering, CAR-Ts, Technology and Procedures, Study Population, Plasma Cell Disorders, Lymphoid Malignancies
ACTR087 expresses a 4-1BB-containing receptor and has been evaluated in combination with rituximab in subjects with relapsed or refractory (R/R) CD20+ B cell lymphoma as previously reported (Akard et al., Blood 2017). SEA-BCMA is a novel, humanized non-fucosylated anti-BCMA IgG1 antibody that has been demonstrated pre-clinically to bind to ACTR087 T cells to mediate ACTR T cell activation, cytotoxicity, cytokine release, and proliferation in the presence of BCMA-expressing MM cell lines. These functional activities were demonstrated to be BCMA-specific and SEA-BCMA dose-dependent (Cheema et al., AACR 2017). Here we present preliminary findings from the first 2 single-subject cohorts of the ATTCK-17-01 study (NCT03266692), an ongoing Phase 1 study of ACTR087 in combination with the first-in-human administration of SEA-BCMA.
Methods: ATTCK-17-01 is a multicenter, Phase 1, dose-escalation study of ACTR087 in combination with SEA-BCMA. The primary objectives are to characterize the safety and to determine the recommended Phase 2 dose of ACTR087 in combination with SEA-BCMA in subjects with R/R MM. The secondary objectives include evaluation of anti-myeloma activity, ACTR T cell persistence, cytokines, and SEA-BCMA pharmacokinetics (PK); exploratory objectives include the anti-myeloma activity of SEA-BCMA alone. Subjects must have measurable disease and must have received at least 3 prior lines of therapy including treatment with a proteasome inhibitor and an immunomodulatory agent, and hematopoietic stem cell transplant (HSCT) for HSCT-eligible subjects. BCMA expression on MM cells was not a condition of eligibility. Dose escalation of the 2 investigational agents, ACTR087 and SEA-BCMA, is determined according to adaptive design principles.
After study enrollment and leukapheresis, subjects receive SEA-BCMA by IV infusion once every 3 weeks until disease progression or treatment discontinuation. After the third dose of SEA-BCMA and lymphodepleting chemotherapy (cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2, each daily for 3 days), subjects receive a single dose of ACTR087.
Results: Two subjects enrolled and received ACTR087 at the first dose level in combination with the first 2 dose levels of SEA-BCMA. First-in-human dosing of SEA-BCMA was well tolerated, with no reported SEA-BCMA-related adverse events (AEs) or dose-limiting toxicities (DLTs).
Following ACTR087 infusion, ACTR+ T cells were detectable in the peripheral blood and demonstrated expansion post-infusion. No DLTs were observed with the combination of ACTR087 and SEA-BCMA in the first 2 cohorts. Grade 3 or higher treatment-emergent AEs experienced by at least 1 subject, regardless of causality assessment, include cytopenias, increased ALT, and bone pain.
Conclusions: ACTR087 in combination with SEA-BCMA was well tolerated in the first 2 subjects treated, with no DLTs or AEs leading to treatment discontinuation. These results support the continued dose escalation of ACTR087 in combination with SEA-BCMA. Enrollment in Cohort 3 is ongoing. Updated data, including SEA-BCMA PK, biomarkers, and preliminary Cohort 3 data, will be presented.
Disclosures: Holmes: Unum: Research Funding; Seattle Genetics: Research Funding, Speakers Bureau; Novartis: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Rigel: Consultancy; Gilead: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy. Hari: Celgene: Consultancy, Honoraria, Research Funding; Kite Pharma: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Spectrum: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding; Janssen: Honoraria; Bristol-Myers Squibb: Consultancy, Research Funding; Amgen Inc.: Research Funding. Sachs: Unum Therapeutics Inc.: Employment. Exter: Unum Therapeutics Inc.: Employment. Ranger: Unum Therapeutics Inc.: Employment. Cheema: Unum Therapeutics Inc.: Employment. Sienczylo: Unum Therapeutics Inc.: Employment. O'Meara: Seattle Genetics: Employment, Equity Ownership. Sussman: Seattle Genetics: Employment. Akard: Gilead: Speakers Bureau; Celgene: Speakers Bureau; Takeda: Speakers Bureau; Novartis: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau.
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