Recently announced data from a Phase 1 trial for investigational T-cell therapy JCAR017 shows a high response rate for patients with relapsed or refractory CD19+ aggressive B-cell non-Hodgkin lymphoma (NHL), according to the potential therapy’s developer, Juno Therapeutics.
JCAR017 is a chimeric antigen receptor (CAR) T-cell product that specifically targets CD19, a protein expressed on the surface of many different B-cell malignancies. When the engineered T-cells interact with the target protein on the cancer cell it initiates a cell-killing response.
The data, presented at the 2017 Annual Meeting of the American Society for Clinical Oncology (ASCO), is from the multicenter TRANSCEND trial, a Phase 1 clinical study that has so far treated 71 patients with aggressive B-cell NHL, including those with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma grade 3B, and mantle cell lymphoma (MCL).
The poster, presented by lead researcher Jeremy Abramson, MD, of Massachusetts General Hospital Cancer Center, was titled, “CR rates in relapsed/refractory (R/R) aggressive B-NHL treated with the CD19-directed CAR T-cell product JCAR017 (TRANSCEND NHL 001).”
The study was designed to assess pharmacokinetics, disease response rates, and safety outcomes, including complications typically associated with CAR T-cell therapies like cytokine release syndrome (CRS) and neurotoxicity.
Patients in this study included those who were excluded from other trials, such as those with central nervous system involvement and patients who had relapsed following allogenic bone marrow transplant, a first for a multicenter trial.
Participants in the study received one of two doses of JCAR017 at 50 million cells or 100 million cells. Combined data from both dose levels showed that 51% of patients had responded to the treatment at three months, including 39% who had complete responses.
The results were particularly positive in a group of 44 patients with DLBCL who were fully functional or unable to perform only strenuous activities. In this group, which the researchers called the “core group,” 66% of patients had responded to JCAR017 at three months. Half of patients were found to have a complete response, meaning that their cancer had been fully eliminated by the treatment.
Additionally, 90% of patients in the core group with a response at three months continued to demonstrate a response at six months. This core group represents the population moving forward into an additional clinical trial, which will take place later this year.
The study also found that 18% of core group patients suffered severe neurotoxicity, while only 2% of patients experienced severe cytokine release syndrome.
“Today’s update of data from the TRANSCEND trial shows continued compelling results in patients with a wide range of aggressive NHL,” Sunil Agarwal, MD, Juno’s president of research and development, said in a press release. “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.”
Juno states that they are currently working on several cell-based products designed to treat a variety of B-cell malignancies as well as solid tumors. It also states that JCAR017 is an investigational therapy candidate and its safety and effectiveness have not yet been established conclusively.