Coming off the back of a series of trial deaths last year and the axing of its once-leading CAR-T treatment JCAR015 at the start of the year, Juno posted new data at ASCO showing some positive data for its second-chance CAR-T, although a death and some neurotoxicity were still present in the data set.
The updated data at ASCO from its Transcend trial is for JCAR017 in relapsed and refractory (r/r) aggressive B cell non-Hodgkin lymphoma (NHL).
This candidate targets CD19, a protein expressed on the surface of almost all B cell malignancies, and uses a defined composition of CD4 to CD8 T cells and a 4-1BB costimulatory domain, which the biotech says “differentiates it from other current CD19-directed CAR T product candidates.”
The phase 1 study has treated 71 patients with r/r aggressive B cell NHL, including those with diffuse large B cell lymphoma (DLBCL), follicular lymphoma grade 3B or mantle cell lymphoma (MCL).
This was a dose-finding study of JCAR017, following preconditioning agents fludarabine/cyclophosphamide lymphodepletion. In total, two analysis groups were presented for the DLBCL cohort: core and full.
The "core" analysis, of 44 patients, includes those that represent the population that will move forward into the biotech’s upcoming pivotal trial, which will begin in the second half of the year. This includes patients with DLBCL (de novo and transformed from follicular lymphoma).
The "full" analysis represents all r/r patients in the DLBCL cohort, 55 patients in all, including the 11 patients with poor performance status or niche subtypes of aggressive NHL.
When combining data across dose levels, the full data set shows the best ORR was 76% (41/54 patients) and CR 52%. And when using the core group, again combining data across dose levels, ORR hit 86% (38/44 patients) and the CR was 59%.
Juno adds that 97% (37/38) of responding patients are alive and in follow up as of May 4, its cut-off date.
But there was one death, an elderly patient in their 80s, in what Juno described as a “Grade 5 adverse event of diffuse alveolar damage, which the investigator assessed as related to fludarabine, cyclophosphamide, and JCAR017 treatment, occurring on day 23.”
The 82-year-old patients was said to have refused mechanical ventilation for progressive respiratory failure, while neutropenic on growth factors and broad-spectrum antibiotics and antifungals.
It also registered 18% (8/44 patients) having “severe neurotoxicity.” It was the fatal rates of neurotoxicity, notably cerebral oedema, that killed 5 patients on Juno’s other CAR-T med last year, leading to its discontinuation.
Juno, now way behind CAR-T rivals Novartis and Kite, was down 7% in early morning trading after the ASCO news.
“Today’s update of data from the Transcend trial shows continued compelling results in patients with a wide range of aggressive NHL,” said Sunil Agarwal, M.D., Juno’s president of R&D.
“We are encouraged by the high rates of durable responses and the early survival data in these patients. We are also encouraged by the early safety data—a majority of patients treated experienced no cytokine release syndrome or neurotoxicity of any grade, which suggests the potential for outpatient administration.”