The FDA placed a clinical hold Wednesday on a phase I trial by Unum Therapeutics Inc. after a patient experienced serious adverse events that included grade 3 neurotoxicity and cytomegalovirus infection, and grade 4 respiratory distress.
The FDA response was another stumble for Unum, which has had an uneven year and a half, during which it saw an underwhelming IPO and the deaths of two patients in the same phase I trial as the company prepped its Wall Street debut.
In late March 2018, Cambridge, Mass.-based Unum priced its IPO of 5.77 million common shares at $12 apiece for gross proceeds of $69.2 million. The company originally sought to raise up to $86 million.
In its S-1 filings nearly a month earlier, Unum wrote of the fatalities that had occurred several months before during the ATTCK-20-2 trial in lymphoma, reporting that two of 17 patients experienced ACTR-087-related severe cytokine release syndrome – one of which died of enterococcal sepsis considered related to ACTR-087 – and another patient experienced treatment-related neurotoxicity that proved fatal. The FDA lifted the hold in February 2018 following review of additional information as well as protocol and dosing changes designed to reduce the incidence of adverse events.
The ATTCK-20-2 study is evaluating Unum's ACTR-087 in combination with rituximab following lymphodepleting chemotherapy with fludarabine and cyclophosphamide in patients with relapsed/refractory (r/r) positive B-cell non-Hodgkin lymphoma (NHL).
When Unum notified the FDA of the latest serious adverse events, the agency halted the trial. The FDA said patients who previously received ACTR-087 and have ongoing clinical responses may continue to receive rituximab infusions, with continued monitoring for adverse events. Unum said it will continue to work closely with the FDA to review those events and it still plans to report data from the ATTCK-20-2 trial at the end of 2019.
Unum's (NASDAQ:UMRX) stock lost 9.1% Tuesday upon news of the clinical hold. Shares regained some ground Wednesday, closing up 1.83%.
That's likely due to the fact that, in November, Unum said it was deprioritizing ACTR-087 as its lead product candidate in combination with rituximab to treat patients with r/r NHL in order to advance its new ACTR construct, ACTR-707, in that setting.
There's also been a C-suite shift at Unum as the company appointed Matthew Osborne chief financial officer, effective June 24, Jessica Sachs chief medical officer, effective July 15, and Mert Aktar head of business and corporate development.
Unum's platform for cancer treatment is based on an antibody-coupled T-cell receptor (ACTR), in which T cells are genetically programmed so that they can go after a variety of cancers via targeting antibodies, and are not restricted by a particular antigen.
The ACTR approach differs from others that are limited to a single target and thus can treat only a narrow set of tumors. That is where the firm's name comes from – Latin, meaning "one," most commonly heard in the phrase "e pluribus unum," meaning "out of many, one." (See BioWorld, Oct. 22, 2014.)
ACTR "takes advantage of CD16, which is really part of the therapy itself," said Unum CEO Charles Wilson. "The way it works is essentially to create a modified T cell that expresses a chimeric receptor. Those engineered T cells are then combined with a tumor-targeting antibody like a Rituxan [rituximab, Roche Holding AG] or a Herceptin [trastuzumab, Roche Holding AG]." CD16 on the surface of the T cells "arms" them and the antibody steers the medicine, he said.
"So, in a patient, basically you would dose the modified T cells and, let's say, Herceptin together. In the body, the Herceptin would find the breast cancer tumor cells, and would serve as a beacon to target the modified T cells to attack the tumor," Wilson told BioWorld at the time. "In some ways, it is similar to what's being done with [chimeric antigen receptors, or CARs] and high-affinity T-cell receptors. What sets it apart is that it really is a universal approach. There's nothing specific about the T cell itself that limits it to one cancer type."