The FDA grants JCAR017 Breakthrough Therapy Designation in DLBCL, NOS, PMBCL, & FL

On 20^th December 2016, JCAR017 (an active CAR T-cell therapy specific to CD19) was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment for patients with DLBCL, PMBCL, grade 3B FL, or Not Otherwise Specified Disease (NOS; de novo or transformed from indolent lymphoma).

Furthermore, on the 15^th December 2016, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) and Committee for Advanced Therapies (CAT) have allowed JCAR017 access to the Priority Medicines (PRIME) scheme (a similar status to the FDA Breakthrough Designation Therapy status) for R/R DLBCL.

The phase I TRANSCEND (NCT02631044) study, which evaluated the safety and pharmacokinetics of Juno Therapeutics’ and Celgene’s investigational drug in R/R NHL patients, was presented at the American Society of Hematology’s 2016 Annual Meeting (abstract 4192) by Jeremy S. Abramson, MD, from the Massachusetts General Hospital, Boston, MA.

• As of 1^st August 2016, 14 patients had been treated at dose level 1 (5 x 10⁷ CAR⁺ T-cells 2–7 days post-lymphodepletion)
  • Thirteen patients had DLBCL, 1 patient had MCL, median age = 61 (range 37–79), medium number of prior therapies = 5 (2–9)
• Of the 14 patients, none developed severe Cytokine Release Syndrome (sCRS); low grade CRS was reported in 3 patients, none required treatment with tocilizumab
• Two patients (14%) with DLBCL had neurotoxicity (grade 4 encephalopathy and grade 4 seizure), both were dose-limiting toxicities
• Two patients with DLBCL died, attributed to disease progression
• Eleven DLBCL patients had ≥1 post-treatment response assessment:
  • At the time of post-treatment assessment on Day 29: OR = 82% (9/11); CR = 73% (8/11); PR = 9% (1/11); PD = 18% (2/11)
  • One patient in CR had a parenchymal brain lesion in the right temporal lobe, which completely resolved
• PK profile of JCAR017 in peripheral blood and bone marrow demonstrated cellular expansion in all patients with persistence of ≥3 months in patients with adequate follow-up

The authors of the abstract concluded by stating that treatment with JCAR017 resulted in high CR rates in heavily pretreated patients with DLBCL. It was also reported that toxicities were manageable and there were fewer AEs reported with JCAR017 compared to other CD19 specific CAR T-cell therapies.

This Breakthrough Therapy Designation emphasizes the need for novel therapies to treat patients with DLBCL, especially for those who are unresponsive to initial treatment or who have relapsed.