FDA puts Unum T cell therapy trial on hold after adverse events

The FDA has put Unum Therapeutics’ phase 1 ACTR087-Rituxan trial on clinical hold for the second time. Unum suffered the setback after a patient experienced grade 3 and 4 adverse events including neurotoxicity and respiratory distress.

ACTR087, an autologous T cell therapy, is designed to bind to cancer cells and then orchestrate their destruction via mechanisms including the release of cytokines and recruitment of immune-mediated killer cells. The potential of the approach established ACTR087 as Unum’s lead asset and enabled the biotech to net $62 million in an IPO for phase 1 and 2 development.

Since then, ACTR087 has slipped down the pecking order at Unum, which stopped enrolling patients in the Rituxan combination trial in the first quarter having made follow-up asset ACTR707 its lead lymphoma candidate. Despite that, investors responded to news of further ACTR087 safety problems by driving Unum’s already-battered stock down almost 20% in premarket trading. 

The safety problems behind the clinical hold center on a patient with relapsed/refractory CD20+ B cell non-Hodgkin lymphoma who suffered grade 4 respiratory distress, plus grade 3 neurotoxicity and cytomegalovirus infection, following treatment.

Those adverse events add to concerns about the safety of ACTR087. Earlier in the trial, Unum chose not to escalate the dose beyond the second level following fatal adverse events. One patient died after suffering neurotoxicity related to ACTR087. Another two patients suffered cytokine release syndrome before dying of sepsis, although only one of the fatal sepsis cases was linked to the drug.

The FDA responded to the adverse events by placing the trial on clinical hold. Unum restarted the study after making protocol and dosing changes designed to reduce the incidence of adverse events and improve their management. 

While ACTR087 is no longer Unum’s lead lymphoma drug, the safety of the asset could still have implications for the company. ACTR087 is in development in combination with Seattle Genetics’ SEA-BCMA in multiple myeloma. And its successor, ACTR707, shares elements of its structure, with the use of a different costimulatory domain—CD28—among the bigger tweaks.