Unum Therapeutics announced the U.S. FDA has placed a clinical hold on the Phase 1 ATTCK-20-2 trial evaluating ACTR087 in combination with rituximab following lymphodepleting chemotherapy with fludarabine and cyclophosphamide in patients with relapsed/refractory CD20+ B cell non-Hodgkin lymphoma (r/r NHL). The clinical hold was placed following the submission of a safety report by Unum to the FDA regarding one patient in the safety expansion cohort of the trial (Cohort 3) who experienced serious adverse events that included Grade 3 neurotoxicity and cytomegalovirus (CMV) infection, and Grade 4 respiratory distress.
This is the second clinical hold the FDA placed on the trial. In March of 2018, during its filing with the U.S. Securities and Exchange Commission, Unum reported ACTR087-related serious adverse events in the second dose level of the ATTCK-20-2 trial, including two patient deaths. One non-ACTR087-related death followed an ACTR087-related severe cytokine release syndrome. The clinical hold was removed in February 2018, following review of information by the FDA.
Despite the clinical hold, the FDA has agreed that patients who previously received ACTR087 and have ongoing clinical responses may continue to receive rituximab infusions, with continued monitoring for adverse events. Unum plans to work with the FDA to further review these events and intends to report data from the ATTCK-20-2 trial at the end of 2019.
About B-cell non-Hodgkin’s lymphoma
B-cell non-Hodgkin’s lymphoma is a sub-type of Non-Hodgkin’s lymphoma, a cancer that originates in the lymphatic system. The lymphatic system is the disease-fighting network spread throughout the body. In non-Hodgkin’s lymphoma, tumors develop from lymphocytes — a type of white blood cell. B cells fight infection by producing antibodies that neutralize foreign invaders. Most non-Hodgkin’s lymphoma arises from B cells.
ACTR087 is an ACTR construct that uses a 4-1BB co-stimulatory domain. Unum’s ACTR product candidates take T cells from patients and then genetically modify them to express the ACTR protein. ACTR is a chimeric protein which combines parts of proteins found on both T cells and natural killer cells to create a powerful attack on cancer cells. The modified cells are then re-administered to the patients with a tumor-specific antibody.