Juno Therapeutics is seeking to change the protocol for the Phase II ROCKET clinical trial of its acute lymphoblastic leukemia candidate JCAR015, which the FDA has placed on clinical hold following the deaths of three patients, two of them last week.
The clinical hold pushes back Juno’s earlier plans to pursue FDA approval next year for JCAR015, a CD19-directed chimeric antigen receptor technology (CAR-T) product candidate that has been under study in ROCKET in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia.
Juno is not discussing a revised development timeframe for JCAR015 until next month, when the company holds its quarterly conference call with analysts.
In a statement yesterday, Juno said it has asked the FDA for permission to change the trial protocol by ending the use of fludarabine as a preconditioning drug along with cyclophosphamide and going back to the trial’s earlier protocol—changed during the second quarter—of cyclophosphamide preconditioning alone. Juno blames the use of fludarabine for the cerebral edema deaths of the three patients, all under age 25.
In response, Juno said, the FDA has asked the company to submit a Complete Response to the Clinical Hold consisting of a revised patient informed consent form, a revised investigator brochure, a revised trial protocol, and a copy of the presentation made to the agency yesterday.
Juno said it will submit the requested information to the FDA this week.
Juno asserted that the clinical hold on the ROCKET trial did not affect plans for its other CD19-directed CAR T-cell product candidates, including JCAR017, for which the company has launched two clinical trials now recruiting patients.
The clinical hold, announced after the close of the NASDAQ market yesterday afternoon, soured investors on Juno enough to send shares of company stock significantly down in after-hours trading that followed a halt just before the announcement. As of 8:35 a.m., shares traded after-hours at $30.58, down 25% from yesterday’s closing price of $40.82.
Juno is among developers of CAR T-cell cancer therapies. One of Juno’s rivals, Kite Pharma, yesterday said it had completed its enrollment of 72 patients with diffuse large B-cell lymphoma in the Phase II portion of the ZUMA-1 trial, designed to assess KTE-C19. The protocol of ZUMA-1 calls for patients to receive fludarabine plus cyclophosphamide for 3 days before infusion of the target dose of KTE-C19, in which a patient's T cells are genetically modified to express a CAR that is designed to target the antigen CD1.