A temporary hold on a phase II trial of Juno Therapeutics’ cancer immunotherapy JCAR015 has been relaxed after a protocol change.
Last week, the US FDA called a halt to the study of the CAR-T therapy after three patient deaths that have now been attributed to a pre-conditioning therapy, which relies on the use of powerful cytotoxic drugs to prime the patient for the immunotherapy.
The agency has said the ROCKET trial can get underway once again, provided one of the pre-conditioning drugs – fludarabine – is no longer given to patients. All the deaths were caused by cerebral oedema, which is a recognised fludarabine side effect, and henceforth all patients in the trial will be given only cyclophosphamide as a pre-conditioning agent.
The cytotoxic drugs are given to patients to kill their existing T cells, clearing the way for the infusion of modified CAR-T cells that have been engineered to attack tumour cells. The ROCKET trial is testing the approach in patients with relapsed or refractory B cell acute lymphoblastic leukaemia (ALL) and is one of the most advanced-stage clinical trials testing the CAR-T approach.
The green light is a relief to Juno but could raise a warning flag for other companies developing CAR-T therapies, which include Novartis, Kite Pharma and Cellectis, among others. The therapeutic approach relies on the use of pre-conditioning regimens and a quick search of clinical trial databases reveals a number of studies that are also using fludarabine.
For now, it is unclear whether the deaths resulted from fludarabine toxicity alone or whether there was some interaction with other variables in Juno’s trial which elevated the risk to patients – including an interaction with the JCAR015 therapy itself.
Shares in Juno and other CAR-T-developing companies plunged last week after the clinical hold was announced, but have since regained a little ground as fears of class-wide implications receded. With billions of dollars already invested in the category, backers will be scrutinising the toxicity data coming out of ROCKET and other CAR-T trials.
Buys RedoxTherapies
Meanwhile, Juno has added to its pipeline with a deal to acquire Boston-based biotech RedoxTherapies and lead compound vidapenant, a small-molecule adenosine 2A receptor antagonist that is thought to have a role as a cancer therapy.
Vipadenant was originally developed as a Parkinson’s disease candidate by UK company Vernalis and licensed to Biogen, but its development was held back by safety concerns and Biogen eventually abandoned the project. RedoxTherapies acquired rights to the drug in 2014.
Juno said that vipadenant has the potential to disrupt immunosuppressive pathways seen in some cancer types, and will test it alongside its existing cancer immunotherapies. The company is paying $10m upfront for RedoxTherapies, but has not disclosed any further terms of the deal.