Juno's ROCKET Trial, Evaluating CAR-T Treatment in Leukemia Patients, Shelved

On an earnings call on March 1, Hans Bishop, president and CEO of Seattle-based Juno Therapeutics, announced that the company has decided to halt the ROCKET trial, also known as the JCAR015 trial. Toxicity associated with the treatment, which resulted in 5 patient deaths, was the primary reason that led to the company’s decision.

In early July 2016, the FDA asked Juno to halt the phase 2 trials of JCAR015 in patients with ALL, citing 3 deaths from cerebral edema. At that point, the company thought that fludarabine in the preconditioning regimen might be the culprit, and in a response to the FDA, Juno proposed leaving the drug out. Convinced by this response, the FDA allowed the HCAR015 trial to resume using cyclophosphamide alone during the preconditioning step.

However, later in the year, 2 more patients on the trial developed cerebral edema and 1 died. The company voluntarily halted JCAR015 again—and has not recovered since. Subsequent investigations by the company identified several different factors that may be responsible for the tragic deaths:

• Patient-specific factors
• Conditioning chemotherapy (fludarabine)
• The CAR-T cells themselves

While the company believes that experimentation with process improvements and protocol changes could allow the JCAR015 trial to proceed, it would need to reestablish safety and dose through another phase 1 study, which would further delay progress.

“2016 was a year of progress and learning for Juno and the cancer immunotherapy field,” Bishop said on the earnings call yesterday. "We continue to experience encouraging signs of clinical benefit in our trial addressing NHL [non-Hodgkin’s lymphoma], but we also recognize the unfortunate and unexpected toxicity we saw in our trial addressing ALL with JCAR015."

The company plans to evaluate a “defined cell product” candidate in adult ALL in 2018.