ICML 2017: Data From the TRANSCEND Trial of JCAR017 in Relapsed and Refractory Aggressive B-Cell Non-Hodgkin Lymphoma
Data from the TRANSCEND trial of JCAR017 in relapsed and refractory aggressive B-cell non-Hodgkin lymphoma (NHL) was presented at the 2017 International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland.
JCAR017 is Juno Therapeutics’ 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-cell product candidates. JCAR017 has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration for treatment of relapsed/refractory aggressive large B-cell NHL and PRIME designation by the European Medicines Agency for treatment of relapsed/refractory diffuse large B-cell lymphoma.
“We are pleased to again present TRANSCEND data, which show compelling results in the treatment of aggressive relapsed or refractory NHL,” said Sunil Agarwal, MD, Juno’s President of Research and Development. “High rates of durable responses and the early survival data are especially exciting, as is the emerging safety profile. The majority of TRANSCEND patients experienced no cytokine-release syndrome or neurotoxicity at all. While still early, these data suggest that JCAR017 could be administered on an outpatient basis.”
Data were presented by Jeremy Abramson, MD, of Massachusetts General Hospital Cancer Center, from the multicenter TRANSCEND trial, a phase I study that has treated a total of 67 patients with relapsed/refractory aggressive B-cell NHL, including those with diffuse large B-cell lymphoma or follicular lymphoma grade 3B, as of a data cutoff date of May 4, 2017.
Trial Details
TRANSCEND NHL 001 is a dose-finding study of JCAR017, which is administered following fludarabine/cyclophosphamide lymphodepletion. Patients received one of two dose levels (50 or 100 million cells). They were then evaluated for pharmacokinetics, disease response, and safety outcomes, including common CAR T-cell side effects such as cytokine-release syndrome and neurotoxicity.
Notably, the TRANSCEND NHL 001 protocol includes patients with forms of B-cell NHL that would exclude them from trials of other CAR T-cell product candidates, including those with ECOG 2 performance status, those with central nervous system involvement of their lymphoma, and those who relapsed after allogeneic bone marrow transplant.
Data for the diffuse large B-cell lymphoma cohort were presented in two groups: core and full. The core analysis group (n = 44) includes patients with diffuse large B-cell lymphoma (de novo and transformed from follicular lymphoma) who have ECOG performance status 0–1. The full analysis group includes all relapsed/refractory patients in the diffuse large B-cell lymphoma cohort (n = 55), including 11 patients with poor performance status or niche subtypes of aggressive NHL. Both the core and full groups received conforming product, with at least 1 month of follow-up and with a data cutoff date of May 4, 2017, for this presentation.
“CAR T-cell therapy represents an important step forward in providing options for these patients with highly chemotherapy-refractory disease and addresses a significant unmet medical need,” said Dr. Abramson. “I am particularly excited about the emerging efficacy and safety profile with JCAR017, which could ultimately prove to be optimal therapy for patients with relapsed and refractory diffuse large B-cell lymphoma.”
Key Data and Findings
Core Group (n = 44)
Combining data across dose levels:
- Overall response rate was 86% (38/44), and the complete response was 59% (26/44)
- 3-month overall response rate was 66% (21/32), and complete response was 50% (16/32). Of patients in response at 3 months, 90% (9/10) continue in response at 6 months
Early data suggest a dose-response relationship at 3 months:
- Dose level 1 (50 million cells) overall response rate was 58% (11/19) and complete response was 42% (8/19)
- Dose level 2 (100 million cells) overall response rate was 78% (7/9) and complete response was 56% (5/9)
Ninety-seven percent (37/38) of responding patients are alive and in follow-up as of May 4, 2017. Two percent (1/44) experienced severe cytokine-release syndrome and 18% (8/44) experienced severe neurotoxicity, but 66% (29/44) did not experience any cytokine-release syndrome or neurotoxicity. No deaths were reported from cytokine-release syndrome or neurotoxicity.
There was one grade 5 adverse event of diffuse alveolar damage, which the investigator assessed as possibly 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, broad-spectrum antibiotics, and antifungals. This patient had no cytokine-release syndrome and grade 3 neurotoxicity resolution before the grade 5 event.
Full Dataset (n = 55)
Combining data across dose levels:
- Best overall response rate was 76% (41/54) and complete response rate was 52% (28/54)
- 3-month overall response rate was 51% (21/41) and complete response rate was 39% (16/41)
Two percent of patients (1/55) experienced severe cytokine-release syndrome, and 16% (9/55) experienced severe neurotoxicity. Sixty percent (33/55) did not experience any cytokine-release syndrome or neurotoxicity. No deaths reported from cytokine-release syndrome or neurotoxicity. Early data do not suggest a dose-toxicity relationship at the doses tested:
- Severe cytokine-release syndrome rate is 3% (1/30) at dose level 1 and 0% (0/19) at dose level 2
- Severe neurotoxicity rate is 20% (6/30) at dose level 1 and 11% (2/19) at dose level 2.
Eleven percent of patients (6/55) received tocilizumab (Actemra), and 24% (13/55) received dexamethasone. The most frequently reported treatment-emergent adverse events were neutropenia (35%), cytokine-release syndrome (35%), and fatigue (31%).
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
