Treatment with the CAR T-cell therapy JCAR017 (lisocabtagene maraleucel, or liso-cel) provided a durable reduction or eradication of cancer in patients with aggressive forms of B-cell non-Hodgkin’s lymphoma (NHL), long-term data from a Phase 1 trial reports.
The data, “Updated safety and long term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagene maraleucel (JCAR017) in R/R aggressive NHL,” will be presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, which opens today and runs through June 5 in Chicago.
The presentation will take place on Sunday, June 3, in a session called Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia.
JCAR017 is an immunotherapy candidate, being developed by Juno Therapeutics and Celgene, to treat patients with aggressive forms of B-cell NHL who have not responded well to other treatments. The investigational medication is a type of CAR T-cell therapy, which modifies a patient’s own immune T-cells to improve their ability to fight cancer.
The multi-center Phase 1 clinical trial (NCT02631044), called TRANSCEND-NHL-001, is testing the safety, pharmacological profile and antitumor activity of JCAR017 in relapsed or refractory patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, follicular lymphoma Grade 3B, and mantle cell lymphoma.
Scientists in the presentation report follow-up data of what they defined as the “FULL” and “non-pivotal” group of patients, which includes all DLBCL patients who received JCAR017, regardless of dose. They also evaluated the treatment’s efficacy in a subgroup called CORE, which included 65 patients with DLBCL or high grade lymphoma from the pivotal group.
In the trial, patients first underwent lymphocyte depletion using fludarabine, a chemotherapy, and cyclophosphamide, and immunossupressant. Intravenous JCAR017 was then tested at multiple doses and administration schedules.
As of Oct. 9, 2017, a total of 91 patients had been treated and analyzed for safety, and 88 of them for treatment efficacy. Cytokine release syndrome (CRS), a form of systemic inflammatory response that can result from treatment with CAR T-cells, occurred in 35% of patients, but only one had severe or life-threatening CRS.
Neurotoxicity was observed in 19% of patients, including 12% with severe or life-threatening complications. It was reported resolved in all but one patient at time of data collection. CRS and neurotoxicity occurred after a median of five and 10 days, respectively. Nineteen patients (21%) were given the immunosuppressive medication Actemra (tocilizumab, Genentech) and/or dexamethasone for these side effects.
Overall response rate (ORR), which refers to a reduction in tumor size over a predefined amount of time, was seen in 74% and 80% of patients in the FULL and CORE groups, respectively, while complete cancer eradication was found in 52% and 55% of patients.
The CORE population showed a higher rate of durable response with a dosing level of 100 million CAR T-cells, with half of patients showing a complete response at six months.
“Liso-cel (JCAR017) shows durable responses in [patients] with heavily pretreated [relapse or refractory] DLBCL,” the scientists wrote.
At the ASCO meeting, the researchers will report long-term safety data , as well as efficacy results at six months (about 95 patients) and 12 months (about 55 patients).
The TRANSCEND-NHL-001 trial is currently recruiting participants at locations across the U.S. For more information, please click here.
Celgene announced plans to acquire Juno in January. Celgene anticipates receiving U.S. Food and Drug Administration approval for JCAR017 sometime in 2019.
