On December 1, 2018 Unum Therapeutics Inc. (NASDAQ: UMRX), reported preliminary results from the ongoing Phase 1 ATTCK-17-01 study, testing ACTR087 in combination with SEA-BCMA in patients with relapsed/refractory multiple myeloma (r/r MM) at the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting in San Diego, CA (Press release, Unum Therapeutics, DEC 1, 2018, View Source [SID1234531761]).
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First-in-human dosing of single agent SEA-BCMA, and of ACTR087 in combination with SEA-BCMA, in the ATTCK-17-01 multi-center, open-label Phase 1 dose-escalation study was well-tolerated, with no dose-limiting toxicities (DLTs) in the first three cohorts. Following infusion, ACTR+ T cells were detectable in these patients and demonstrated expansion post infusion. Furthermore, early disease assessments suggest combination activity of SEA-BCMA with ACTR087. These data support continued dose escalation of ACTR087 and SEA-BCMA in the trial.
"We are pleased with the early data we have observed showing biomarker evidence of antibody-dependent ACTR T cell activation at the lowest doses of SEA-BCMA," said Michael Vasconcelles, Chief Medical Officer of Unum. "Combining ACTR087 with a novel antibody like SEA-BCMA brings together multiple anti-myeloma mechanisms of action that are unique to this combination. Furthermore, this approach provides us the ability to adjust the doses of both the antibody and ACTR087, to optimize the therapeutic index of the combination. We are excited about the potential to develop a meaningful combination for patients with relapsed or refractory myeloma. We look forward to continued dose escalation of the combination in ATTCK-17-01 to further assess its safety and anti-myeloma activity."
The majority of subjects, including at the lowest SEA-BCMA dose levels, demonstrated increasing serum and urine M protein levels during SEA-BCMA single-agent dosing that stabilized or decreased following ACTR087 administration, suggesting combination activity of ACTR087+SEA-BCMA. Subjects exhibited early increases in interferon gamma following ACTR087 administration, and additional elevations following subsequent SEA-BCMA administrations, suggestive of antibody-dependent T cell activation. SEA-BCMA was well-tolerated with no serious adverse events related to SEA-BCMA reported. No DLTs after the SEA-BCMA single-agent dosing period or after the ACTR087 + SEA-BCMA combination were reported across all three cohorts. No severe events of cytokine release syndrome (CRS) or severe neurological events were reported.
About the ATTCK-17-01 Trial
ACTR087 used in combination with SEA-BCMA is being tested in ATTCK-17-01, a Phase I, multi-center, open-label clinical trial designed to test the safety, tolerability, and anti-myeloma activity in patients with r/r MM, currently in the dose escalation phase. Primary study objectives are to characterize the safety of ACTR087 in combination with SEA-BCMA and to determine the recommended Phase 2 dose. Secondary study objectives include assessment of the anti-myeloma activity of the combination, ACTR T cell expansion and persistence, cytokine and SEA-BCMA pharmacokinetics. Immediately following leukapheresis, patients may begin to receive SEA-BCMA as a single agent. Following lymphodepleting chemotherapy, a single ACTR087 infusion is administered. This is the first clinical trial conducted under the Company’s strategic collaboration with Seattle Genetics.
About ACTR087 in combination with SEA-BCMA
ACTR087 is a 4-1BB-containing receptor that also has been evaluated in combination with rituximab in adult patients with relapsed or refractory non-Hodgkin lymphoma (r/r NHL). SEA-BCMA is a novel humanized non-fucosylated antibody that targets the antigen BCMA, developed by Seattle Genetics using the Company’s sugar-engineered antibody (SEA) technology. BCMA is expressed on normal plasma cells, some mature B cells, and at comparatively elevated levels on malignant multiple myeloma cells but is absent from other normal tissues. SEA-BCMA is engineered to enhance its binding to ACTR087, providing additional rationale for this novel-novel combination.