Juno Therapeutics, a biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer, has announced, in partnership with its collaborators, early clinical data from two product candidates.

JCAR018 is a chimeric antigen receptor (CAR) T cell product candidate targeting CD22, and had data from a phase I trial in pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r ALL). JTCR016, a T cell receptor (TCR) cell product candidate targeting Wilms tumor-1 (WT-1), had data from a phase I trial in patients with acute myelogenous leukemia (AML) at high risk of relapse following an allogeneic hematopoietic stem cell transplant and patients with either mesothelioma or non-small cell lung cancer.

“As we advance our CD19-directed portfolio, we are encouraged by the early signs of clinical activity from product candidates against different targets,” said Mark J. Gilbert, M.D., Juno’s chief medical officer. “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. 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.”

Terry J. Fry, M.D., investigator, Pediatric Oncology Branch and head of Hematologic Malignancies Section, National Cancer Institute, National Institutes of Health, reported on CD22-directed CAR T cell therapy (JCAR018) in pediatric and young adult patients with r/r B-cell ALL. Key takeaways include:

• Data from nine enrolled and treated patients were reported in this phase I dose-escalation trial.
• As previously reported, six patients were treated at the lowest dose, with one patient achieving a complete remission (CR) and complete molecular remission as measured by flow cytometry (CmR). This patient relapsed after three months.
• Three patients have enrolled at dose level 2 (1 x 106 cells/kg), which is in the dose range of CD19-directed CAR T programs. All three patients achieved a CR and CmR. These patients remain in complete remission with follow-up ranging from three to six months.
• The complete remissions have been seen in both patients naïve to CAR T therapies as well as those with CD19 negative relapse after prior CD19-directed CAR T therapy.
• Limited cytokine release syndrome (CRS) was seen at dose level 2, with two patients at Grade 1 and one patient at Grade No severe neurotoxicity was observed in these treatment cohorts. Dose limiting toxicity was observed at higher doses, so dosing continues at dose level 2 (1 x 10⁶cells/kg).

Phil Greenberg, M.D., head of Program in Immunology at the Fred Hutchinson Cancer Research Center, and professor, Medicine/Oncology and Immunology, University of Washington, reported on WT-1 TCR cell therapy (JTCR016) in refractory mesothelioma and AML. Key takeaways include:

• In a phase I/II study designed to evaluate genetically modified T cells targeting WT-1 in WT-1-expressing non-small cell lung cancer (NSCLC) and mesothelioma using a WT-1-specific T-cell receptor, WT-1 TCR. There have been five patients enrolled.
• Three patients have been treated to date. Preliminary data show one mesothelioma patient with an ongoing partial response to the WT-1 TCR and one with stable disease. The responses appear to correlate with the pharmacokinetics of the engineered T cells, as the patient with the partial response had the best T cell expansion and persistence. The patient had progressed after multiple therapies, including chemotherapy and radiation, prior to receiving JTCR016.
• JTCR016 was generally well-tolerated in these three patients, with no evidence of severe CRS or severe neurotoxicity.
• In a phase I dose-escalation trial in patients with AML following allogeneic hematopoietic stem cell transplantation, 11 patients with no measurable disease but at high risk of relapse have been treated to date. JTCR016 continues to be relatively well-tolerated with prolonged persistence of the engineered T cells and no relapses to date.