June 5, 2017
By Mark Terry, BioSpace.com Breaking News Staff
It was only two months ago in early March when Juno Therapeutics announced it was shuttering its lead CAR-T oncology program, JCAR015, because of patient deaths. Now, it looks like the company has bounced back with positive interim data from its other CAR-T program, JCAR017, presented at the ASCO meeting in Chicago.
Juno announced updated data from its TRANSCEND trial of JCAR017 in relapsed and refractory (r/r) aggressive B cell non-Hodgkin lymphoma (NHL). This CAR-T product targets CD19, a protein found on the surface of most B-cell malignancies. The company notes that it “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.”
The trial so far has shown a combined overall response rate (ORR) of 86 percent and a complete response rate of 59 percent, or 26 of 44 patients. At three months, the ORR was 66 percent with a 50 percent CRR. As of May 4, 37 of the 38 patients that responded were still alive.
The death was of an 82-year-old patient with diffuse alveolar damage linked to the drug and the flu/cy conditioning treatment that is utilized to prepare patients.
Cytokine release syndrome (CRs) is a very common and life-threatening adverse affect of CAR-T therapy, and was largely behind the shuttering of the JCAR015 program. It is essentially an overreaction by the immune system that creates severe inflammation and what often look like allergic reactions. In this most recent study of JCAR017, only one patient had CRs that was severe but not fatal, although 18 percent of the patients, 8, showed neurotoxicity.
“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, Juno’s president of Research and Development, in a statement. “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.”
Although there are a number of companies working with CAR-T, and who are presenting data at ASCO, the most obvious competitor for Juno is Kite Pharma . Interim data from Kite’s ZUMA-1 trial in 55 relapsed, refractory DLBCL patients with its axi-cel had a complete response rate of 33 percent and an overall response rate of 39 percent. Two patients died. Severe cytokine release syndrome was 18 percent and neurotoxicity was 34 percent.
Adam Feuerstein, writing for TheStreet, says, “Juno’s new JCAR017 data come from a smaller number of patients with less follow up, but so far, the data stack up well against Kite. A Kite spokesperson pushes back against making direct comparisons between JCAR017 and axi-cel, saying the two companies define DLBCL differently.”
Another comparison would be with Novartis , who on May 31 released terrific results for CTL019, its CAR-T product, in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who had been on Imbruvica (ibrutinib) for at least six months, but were not in complete remission. Of the 10 patients treated, eight showed no signs of CLL in their bone marrow; one had a partial response, the remaining did not produce evaluable data.
But Novartis is also evaluating CTL019 in DLBCL and plans to release interim results from its JULIET trial at a European blood cancer meeting on June 14.
