Seattle, Washington-based Juno Therapeutics and partners recently announced two immunotherapeutic candidates with promising clinical responses in patients with B-cell leukemia and mesothelioma. The early clinical data was presented at the American Association for Cancer Research (AACR) Annual Meeting 2016 in New Orleans, Louisiana, in two distinct oral presentations.
In the first presentation, “CD22 CAR Update and Novel Mechanisms of Leukemic Resistance,” Dr. Terry J. Fry, M.D, investigator in the Pediatric Oncology Branch and head of Hematologic Malignancies Section of the National Cancer Institute of the National Institutes of Health, showed data from nine pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r ALL) who enrolled in a Phase 1 trial.
Patients were treated with a chimeric antigen receptor (CAR) T-cell product candidate — JCAR018 — that targets CD22. This immuno construct is generated using a technology that inserts a CAR gene into T-cells, allowing them to recognize malignant cells that bear a specific protein (CD22) on their cell surface, initiating a killing response against cancer cells.
Of the nine patients, six were treated at the lowest dose. One patient entered a complete remission and a complete molecular remission, but relapsed after three months. The other three patients who achieved complete and complete molecular remission were treated with a dose level that is within the range of CAR T programs directed against CD19, and below dose limiting toxicity. Patients who reached complete remissions either had never been treated with CAR T therapies in the past, or had had a CD19-negative relapse following CAR T therapy directed against CD19.
The second study reported a Phase 1/2 trial evaluating genetically modified T-cells bearing a T-cell receptor (TCR) specific for Wilms tumor-1 (WT-1) protein — JTCR016, in patients with WT-1 positive non-small cell lung cancer (NSCLC) and mesothelioma. The study, “Targeting Cancer with Engineered T Cells,” was presented by Dr. Phil Greenberg, M.D., head of program in Immunology at the Fred Hutchinson Cancer Research Center and professor of medicine/oncology and immunology at the University of Washington.
To date, three patients were treated, with one mesothelioma patient that had been previously subjected to chemotherapy and radiation without success revealing partial response to the WT-1 TCR therapy, and another achieving stable disease. The patient with partial response had higher T-cell persistence and expansion than other patients, suggesting that responses to treatment correlated with the pharmacokinetics of the engineered T-cells.
JTCR016 was also evaluated in patients with acute myeloid leukemia (AML) subjected to hematopoietic stem cell trasplantation, in a Phase 1 dose-escalation trial. Eleven patients at high risk of relapse but no measurable disease have been treated with JTCR016. To date, none of the patients have relapsed and the engineered T-cells have been somewhat well-tolerated and have persisted for long periods.
“The data from JCAR018 suggest two paths to improve outcomes – use in patients with CD19 negative disease and a combination of CD19 and CD22 to decrease the risk of resistant cells and increase the percentage of patients that demonstrate a long-term durable remission in B-cell malignancies,” said Dr. Mark J. Gilbert, M.D., Juno’s chief medical officer, in a press release.
“Additionally, JTCR016 continues to show an encouraging safety profile and signals of clinical activity, including evidence of tumor reduction as well as significant T-cell expansion and persistence in a patient with mesothelioma,” Gilbert said.