JCAR017 is Juno’s investigative chimeric antigen receptor (CAR) T cell product candidate that 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 differentiates it from other current CD19-directed CAR T product candidates.
“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 Research and Development.
“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.”
The data presented today by principal investigator Jeremy Abramson, M.D., of Massachusetts General Hospital Cancer Center, were from the multicenter TRANSCEND trial (ASCO Abstract #7513), a Phase 1 study that 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 fludarabine/cyclophosphamide lymphodepletion.
Patients were evaluated for pharmacokinetics, disease response, and safety outcomes, including those commonly associated with CAR T cell therapy, such as cytokine release syndrome (CRS) and neurotoxicity (NT). Patients in this study included those excluded from other trials, including those with ECOG 2 performance status, central nervous system (CNS) involvement of their lymphoma, and those relapsed after allogeneic bone marrow transplant.
Two analysis groups were presented for the DLBCL cohort, core and full. The core analysis (N=44) includes patients that represent the population that will move forward into the upcoming pivotal trial, which will begin in the second half of 2017. This includes patients with DLBCL (de novo and transformed from follicular lymphoma) that are ECOG Performance Status 0-1. The full analysis represents all r/r patients in the DLBCL cohort (N=55), including the 11 patients with poor performance status or niche subtypes of aggressive NHL. Both analysis groups are with conforming product, with at least one month follow up, and with a data cutoff date of May 4, 2017, for this presentation.
Key data and findings:
Core Group
Combining data across dose levels:
Overall response rate (ORR) is 86% (38/44) and the complete response (CR) is 59% (26/44).
Three-month ORR is 66% (21/32) and CR is 50% (16/32). Of three-month responders followed up at least six months, 90% (9/10) remain in response.
Early data suggest a dose response relationship at three months:
Dose level 1 (50 million cells) ORR is 58% (11/19) and CR is 42% (8/19).
Dose level 2 (100 million cells) ORR is 78% (7/9) and CR is 56% (5/9).
97% (37/38) of responding patients are alive and in follow up as of May 4, 2017.
2% (1/44) experienced severe CRS and 18% (8/44) experienced severe NT.
66% (29/44) did not experience any CRS or NT. No deaths were reported from CRS or NT.
There was one Grade 5 adverse event of diffuse alveolar damage, which the investigator assessed as related to fludarabine, cyclophosphamide, and JCAR017 treatment, occurring on day 23 in an 82-year-old subject who refused mechanical ventilation for progressive respiratory failure while neutropenic on growth factors and broad spectrum antibiotics and antifungals.
Full Dataset
Combining data across dose levels:
Best ORR is 76% (41/54) and CR is 52% (28/54).
Three-month ORR is 51% (21/41) and CR is 39% (16/41).
2% (1/55) experienced severe CRS and 16% (9/55) experienced severe NT. 60% (33/55) did not experience any CRS or NT. No deaths reported from CRS or NT.
Early data do not suggest a dose toxicity relationship at the doses tested:
Severe CRS rate is 3% (1/30) at dose level 1 and 0% (0/19) at dose level 2.
Severe NT rate is 20% (6/30) at dose level 1 and 11% (2/19) at dose level 2.
11% (6/55) received tocilizumab and 24% (13/55) received dexamethasone.
The most frequently reported treatment-emergent adverse events were neutropenia (35%), CRS (35%), and fatigue (31%).
Manufacturing
Product was available for 98% (86/88) of patients apheresed, and product that met specification was available for 89% (78/88) of patients.