After a torrid year that has seen multiple deaths in testing, FDA- and self-imposed study halts and its shares tanking, Juno last night held up to the light its new great hope: JCAR017
Juno said that its med, which uses a defined CD4:CD8 cell composition and 4-1BB as the costimulatory domain, saw a 60% complete response rate in the small phase 1 test, hitting its marks in 12 out of 20 patients.
The trial looked at patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL), follicular lymphoma grade 3B or mantle cell lymphoma, and were treated with fludarabine/cyclophosphamide lymphodepletion and JCAR017.
In terms of safety, the issue most observers were scrutinizing, the biotech said that of the 22 safety-evaluable patients (the majority being DLBCL patients) treated at a dose level 1 and with a single-dose schedule, “no severe cytokine release syndrome (sCRS) was observed.”
They did however see grades 3-4 neurotoxicity in three patients (14%), all of whom received the steroid dexamethasone for neurotoxicity, but the company said this dealt with the issue.
The most frequently reported treatment-emergent adverse events were neutropenia (a common problem in cancer treatments, which hit all patients in the test), decreased appetite (36%) and fatigue (32%). Crucially for the company however, no deaths were recorded.
The so-called Transcend study continues with what is now surely Juno’s leading product, enrolling more patients at dose levels 1 and 2.
The biotech said that it intends to start a pivotal trial in the U.S. in patients with r/r DLBCL next year.
“Our potential best-in-class CAR T candidate, JCAR017, has demonstrated an impressive early response rate in these sick NHL patients,” said Mark Gilbert, Juno’s CMO.
“In particular, the side effect profile and persistence of CAR T cells that we observed, even in patients who relapsed, will allow us to explore higher doses and the possibility for combination therapies to potentially increase durable response rates.”
Just a few weeks ago, Juno put its midstage CAR-T Rocket trial put on hold after two patients suffered cerebral edema, both of whom later died.
The phase 2 study, which was voluntarily halted, was assessing JCAR015, formerly its leading med, in patients with relapsed or refractory B cell acute lymphoblastic leukemia.
This comes after the FDA placed a brief clinical hold on the same Rocket trial of JCAR015 in July after several patient deaths, also due to cerebral edema.
The FDA halt was however swiftly lifted a few days later, but with a modified preconditioning regimen that it said would stop future patient deaths.
The biotech was at the time adamant that the chemo med fludarabine used as a preconditioning regimen was the primary culprit in the fatalities, although it now appears there may be more to the deaths than just the flu regimen.
Both Novartis and Kite have now taken the lead in the CAR-T space, announcing over the weekend that they are planning full FDA submissions early next year, with Bluebird Bio picking up the rear.