Juno’s (JUNO) JCAR017 and JCAR014 are chimeric antigen receptor T cell (CAR-T) product candidates that target CD19, a protein expressed on the surface of almost all B cell malignancies. These malignancies include non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and acute lymphoblastic leukemia (ALL).
The clinical trial results of Juno’s CAR-T product JCAR017 in relapsed and refractory (r/r) aggressive B cell non-Hodgkin lymphoma (NHL) are promising. Juno believes that using a defined composition of CD4 to CD8 T cells and a 4-1BB co-stimulatory domain might distinguish its products from other firms’ CAR-T products targeting CD19.
The phase 1 study recruited 71 patients with r/r aggressive B cell NHL, including those having diffuse large B cell lymphoma (DLBCL), follicular lymphoma grade 3B or mantle cell lymphoma (MCL). There was preconditioning with fludarabine/cyclophosphamide lymphodepletion prior to the CAR-T usage.
In total, two analysis, Core and Full, were presented for the DLBCL cohort.
The core analysis of 44 patients, includes those that represent the population, which will move forward into the upcoming pivotal trial. This study will begin in the second half of the year. It 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.
Combined data across dose levels:
Using the full data: ORR was 76% (41/54 patients) and CR 52%.
Using the core group: ORR was 86% (38/44 patients) and CR was 59%.
We learned from the firm that 97% (37/38) of responding patients are alive and in follow up as of May 4, its cut-off date.
One death occurred to a patient over 80 years old.
Juno described the incidence as a “Grade 5 adverse event of diffuse alveolar damage attributed to fludarabine, cyclophosphamide, and JCAR017 treatment, occurring on day 23.
It is to be noted that the investigators tried to save the man’s life, suggesting mechanical ventilation for his progressing respiratory failure, but he refused the procedure.
Adverse events included 18% (8/44 patients) having “severe neurotoxicity.”
What makes us assure that the CAR-T approach is created to live and supervene and will be approved and improved is the fact that this treatment makes miracles compared to other conventional treatments. It makes the condemned survive, which is why the FDA considers the rewards outweigh the risks. The severe AEs occur to a small percentage of the patients treated with the CAR-T and the AEs are being circumvented.
Who should not forget that if not given the CAR-T treatments the advanced stage cancer patients would have all died.
Moreover, as we kept repeating, many academic institutions and other research institutions, in addition to biotech and pharmaceutical companies are working on solutions to prevent the occurrence of the severe adverse effects and to make the treatment effective in solid cancers.
At ASCO, Sunil Agarwal, M.D., Juno’s president of R&D said, “Today’s update of data from the TRANSCEND trial shows continued compelling results in patients with a wide range of aggressive NHL. We are encouraged by the high rates of durable responses and the data about patients’ survival. We are also encouraged by the early safety data—a majority of patients treated experienced no early cytokine release syndrome or neurotoxicity of any grade, which suggests the potential for outpatient administration.”
Many CAR-T developers are already improving the safety of their immunotherapy approach. We mentioned a few yesterday and we believe that Juno is doing the right think with its CAR-T approach following the halting of one of its products for serious adverse events.
We will update the information about the CAR-T CELL firms. Our Prohost Letter #411 will be dedicated to this immune-oncology process and all the firms creating and developing these treatments.
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