On April 20, 2016 Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer, reported, in partnership with its collaborators, early clinical data from two oral presentations for two product candidates at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans, Louisiana (Press release, Juno, APR 20, 2016, View Source;p=RssLanding&cat=news&id=2158810 [SID:1234511172]).

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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."

In an oral presentation on Monday, April 18, 2016, Terry J. Fry, M.D., Investigator, Pediatric Oncology Branch and Head of Hematologic Malignancies Section, National Cancer Institute, National Institutes of Health, presented "CD22 CAR Update and Novel Mechanisms of Leukemic Resistance." Dr. Fry 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. (JCAR018; Clinical Trials Identifier: NCT02315612).

As previously reported at the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting in December 2015, 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 3 to 6 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 2. 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 106 cells/kg).

In an oral presentation on Wednesday, April 20, 2016, 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, presented "Targeting Cancer with Engineered T Cells." Dr. Greenberg 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 (JTCR016; Clinical Trials Identifier: NCT02408016), 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.

This AACR (Free AACR Whitepaper) 2016 Major Symposium presentation also highlighted encouraging pre-clinical data from a mesothelin-directed TCR for the treatment of pancreatic cancer, demonstrating the potential of these therapies in treating solid tumors, and next-generation strategies to make these T cells more potent.

About Juno’s Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR) Technologies
Juno’s CAR and TCR technologies genetically engineer T cells to recognize and kill cancer cells. Juno’s CAR T cell technology inserts a gene for a particular CAR into the T cell, enabling it to recognize cancer cells based on the expression of a specific protein located on the cell surface. Juno’s TCR technology provides the T cells with a specific T cell receptor to recognize protein fragments derived from either the surface or inside the cell. When either type of engineered T cell engages the target protein on the cancer cell, it initiates a cell-killing response against the cancer cell. JCAR018 and JTCR016 are investigational product candidates and their safety and efficacy have not been established.