Juno Therapeutics’s CAR T and TCR Investigational Product Candidates Demonstrate Promising Outcomes In Clinical Trials In Patients With B-Cell Cancers
SEATTLE--(BUSINESS WIRE)--Juno Therapeutics, Inc. announced today that clinical data from its most advanced chimeric antigen receptor (CAR) product candidates, JCAR017, JCAR015 and JCAR014, demonstrated encouraging evidence of clinical responses in acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL). Clinical results were presented in oral and poster presentations at the 56th American Society of Hematology (ASH) Annual Meeting in San Francisco, California.
Highlights from the research include:
• High rates of tumor reduction in B-cell malignancies, including complete remission rate of 89% in adult relapsed/refractory B-cell ALL with JCAR015. • Robust T cell expansion and persistence and clinical remissions with JCAR017. • Potential for prolonged T cell persistence with WT-1, a high-affinity T cell receptor (TCR) candidate, in acute myeloid leukemia (AML). • Association of cell expansion and persistence with clinical outcome.
“The tumor response rates and duration observed in these ongoing studies remain encouraging as we advance our lead product candidates in hematological malignancies,” said Juno CEO, Hans Bishop. 1. In an oral presentation on the Phase I clinical trial results of JCAR015 in adults with ALL, Jae H. Park, M.D. of the Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, in New York City, presented:
• Complete remission occurred in 24/27 (89%) evaluable patients and complete molecular remission occurred in 21/24 (88%) evaluable patients with relapsed/refractory adult ALL.
• In this ongoing trial, median overall survival was 8.5 months. Durable responses were observed in patients with and without subsequent allogeneic stem cell transplant.
• Cytokine release syndrome (CRS) requiring vasopressors and/or mechanical ventilation was required for 5/15 patients with morphologic disease, or greater than 5% blasts in the bone marrow, and 0/13 patients without morphologic disease. Grade 3/4 neurotoxicity occurred in 7/28 patients and was generally reversible.
2. In an oral presentation on the Phase I clinical trials results of JCAR015 in patients with B-cell NHL, Craig S. Sauter, M.D., of the Department of Medicine, Memorial Sloan Kettering Cancer Center, presented:
• At a median follow-up of 9 months (range 1-17.5), 6/6 (100%) patients with poor-risk, relapsed/refractory aggressive B cell NHL remain alive and in remission after treatment with high dose chemotherapy and autologous stem cell transplantation, followed by CD19-directed CAR T cell therapy. Two patients remain alive more than one year from treatment.
• One patient treated with 1 x107 CAR T/kg experienced severe CRS.
3. In a poster presentation on the Phase I clinical trials results of JCAR017 in pediatric patients with ALL, Rebecca A. Gardner, M.D., of Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, in Seattle, presented:
• Eleven of 13 (85%) patients with relapsed/refractory ALL following allogeneic stem cell transplantation obtained or maintained an MRD negative complete remission following CAR T cell therapy.
• All 11 responding patients exhibited in vivo expansion of CAR T cells (median peak CAR+ T cells of 478/uL [range 63-1288] occurring 7-14 days post infusion), with 6/8 (75.0%) of evaluable patients having CAR T cell persistence of more than 40 days.
• Two patients received treatment with steroids and tocilizumab for severe cytokine release syndrome. One of these patients experienced grade 4 encephalopathy and there was an additional patient that experienced grade 3 encephalopathy.
4. In an oral presentation on the Phase I clinical trials results of JCAR014 in patients with relapsed/refractory ALL, NHL and chronic lymphocytic leukemia (CLL), Cameron J. Turtle, MBBS, Ph.D., of the Clinical Research Division, Fred Hutchinson Cancer Research Center, in Seattle, presented: • In patients receiving defined composition products, responses were observed in 6/10 (60%) evaluable NHL patients, and 2/2 evaluable CLL patients, complete remission occurred in 11/11 (100%) patients and complete molecular remissions occurred in 9/11 (82%) patients with ALL.
• A subset of NHL patients tested in whom CAR-T cells became undetectable developed a T cell immune response to sequences in the murine CD19-specific single-chain variable fragment (scFv) component of the CAR transgene.
•Severe CRS was observed in 3/13 (23%) ALL patients, including one death, and in 0/14 evaluable NHL/CLL patients. Grade 3 delirium was observed in one patient with CLL.
5. In a poster presentation on the Phase I/II clinical trial results of WT-1 in post-transplant patients with AML, Merav Bar, M.D., of the Fred Hutchinson Cancer Research Center, presented: • Escalating doses of donor-derived virus specific CD8+ T cells transduced to express a high-affinity TCR specific for the HLA A*02:01-restricted WT1126-134 (RMFPNAPYL) epitope were administered in high-risk AML patients after allogeneic hematopoietic stem cell transplantation.
• WT-1 specific T cell delivery was generally well tolerated.
• 13/15 patients remain alive with follow-up for up to 18 months.
•12/15 have ongoing detectable WT-1 cells with follow up ranging from 5 to 368 days from the last infusion.
About Juno’s Chimeric Antigen Receptor and High-affinity T Cell Receptor Platform
Juno is developing cell-based immunotherapies based on its chimeric antigen receptor, or CAR, and high-affinity T cell receptor, or TCR, platform to genetically engineer T cells to recognize and kill cancer cells. T cells are a type of white blood cells that identify and kill infected or abnormal cells, including cancer cells, in healthy individuals. Juno leverages its CAR and TCR platform to activate a patient’s own T cells so that they attack cancer cells. Through genetic engineering, a gene is inserted for a particular CAR or TCR construct into the T cell enabling it to better recognize cancer cells. The CAR technology directs T cells to recognize cancer cells based on the expression of specific proteins located on the cell surface, whereas the 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. CAR constructs typically use a single chain variable fragment, or scFv, to recognize a protein of interest. The modified T cells can be infused into the patient or frozen and stored for later infusion.
About Juno
Juno Therapeutics, Inc. is building a fully integrated biopharmaceutical company focused on revolutionizing medicine by re-engaging the body’s immune system to treat cancer. Founded on the vision that the use of human cells as therapeutic entities will drive one of the next important phases in medicine, Juno is developing cell-based cancer immunotherapies based on chimeric antigen receptor and high-affinity T cell receptor technologies to genetically engineer T cells to recognize and kill cancer. Juno is developing multiple cell-based product candidates to treat a variety of B-cell malignancies as well as solid tumors. Several product candidates have shown compelling evidence of tumor shrinkage in the clinical trials in refractory leukemia and lymphoma conducted to date. The company’s long-term aim is to improve and leverage its cell-based platform to develop new product candidates that address a broader range of cancers and human diseases. Juno brings together innovative technologies from some of the world’s leading research institutions, including the Fred Hutchinson Cancer Research Center, Memorial Sloan Kettering Cancer Center, and Seattle Children’s Research Institute.
www.JunoTherapeutics.com
Forward Looking Statements
This press release contains forward-looking statements, including statements regarding the clinical development of our product candidates, the safety and efficacy of our product candidates as well as their potential, and the encouraging nature of clinical data observed to date. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: risks associated with the success, cost and timing of our product development activities and clinical trials; the approval and commercialization of our product candidates; and risks of increased regulatory requirements, amongst others. These forward-looking statements speak only as of the date hereof. Juno Therapeutics disclaims any obligation to update these forward-looking statements.
Contacts
W2O Group
Investor Relations:
David Walsey, 858-617-0772
dwalsey@w2ogroup.com
or
Media:
Andreas Marathovouniotis, 212-301-7174
amarathis@w2ogroup.com
Help employers find you! Check out all the jobs and post your resume.
Highlights from the research include:
• High rates of tumor reduction in B-cell malignancies, including complete remission rate of 89% in adult relapsed/refractory B-cell ALL with JCAR015. • Robust T cell expansion and persistence and clinical remissions with JCAR017. • Potential for prolonged T cell persistence with WT-1, a high-affinity T cell receptor (TCR) candidate, in acute myeloid leukemia (AML). • Association of cell expansion and persistence with clinical outcome.
“The tumor response rates and duration observed in these ongoing studies remain encouraging as we advance our lead product candidates in hematological malignancies,” said Juno CEO, Hans Bishop. 1. In an oral presentation on the Phase I clinical trial results of JCAR015 in adults with ALL, Jae H. Park, M.D. of the Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, in New York City, presented:
• Complete remission occurred in 24/27 (89%) evaluable patients and complete molecular remission occurred in 21/24 (88%) evaluable patients with relapsed/refractory adult ALL.
• In this ongoing trial, median overall survival was 8.5 months. Durable responses were observed in patients with and without subsequent allogeneic stem cell transplant.
• Cytokine release syndrome (CRS) requiring vasopressors and/or mechanical ventilation was required for 5/15 patients with morphologic disease, or greater than 5% blasts in the bone marrow, and 0/13 patients without morphologic disease. Grade 3/4 neurotoxicity occurred in 7/28 patients and was generally reversible.
2. In an oral presentation on the Phase I clinical trials results of JCAR015 in patients with B-cell NHL, Craig S. Sauter, M.D., of the Department of Medicine, Memorial Sloan Kettering Cancer Center, presented:
• At a median follow-up of 9 months (range 1-17.5), 6/6 (100%) patients with poor-risk, relapsed/refractory aggressive B cell NHL remain alive and in remission after treatment with high dose chemotherapy and autologous stem cell transplantation, followed by CD19-directed CAR T cell therapy. Two patients remain alive more than one year from treatment.
• One patient treated with 1 x107 CAR T/kg experienced severe CRS.
3. In a poster presentation on the Phase I clinical trials results of JCAR017 in pediatric patients with ALL, Rebecca A. Gardner, M.D., of Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, in Seattle, presented:
• Eleven of 13 (85%) patients with relapsed/refractory ALL following allogeneic stem cell transplantation obtained or maintained an MRD negative complete remission following CAR T cell therapy.
• All 11 responding patients exhibited in vivo expansion of CAR T cells (median peak CAR+ T cells of 478/uL [range 63-1288] occurring 7-14 days post infusion), with 6/8 (75.0%) of evaluable patients having CAR T cell persistence of more than 40 days.
• Two patients received treatment with steroids and tocilizumab for severe cytokine release syndrome. One of these patients experienced grade 4 encephalopathy and there was an additional patient that experienced grade 3 encephalopathy.
4. In an oral presentation on the Phase I clinical trials results of JCAR014 in patients with relapsed/refractory ALL, NHL and chronic lymphocytic leukemia (CLL), Cameron J. Turtle, MBBS, Ph.D., of the Clinical Research Division, Fred Hutchinson Cancer Research Center, in Seattle, presented: • In patients receiving defined composition products, responses were observed in 6/10 (60%) evaluable NHL patients, and 2/2 evaluable CLL patients, complete remission occurred in 11/11 (100%) patients and complete molecular remissions occurred in 9/11 (82%) patients with ALL.
• A subset of NHL patients tested in whom CAR-T cells became undetectable developed a T cell immune response to sequences in the murine CD19-specific single-chain variable fragment (scFv) component of the CAR transgene.
•Severe CRS was observed in 3/13 (23%) ALL patients, including one death, and in 0/14 evaluable NHL/CLL patients. Grade 3 delirium was observed in one patient with CLL.
5. In a poster presentation on the Phase I/II clinical trial results of WT-1 in post-transplant patients with AML, Merav Bar, M.D., of the Fred Hutchinson Cancer Research Center, presented: • Escalating doses of donor-derived virus specific CD8+ T cells transduced to express a high-affinity TCR specific for the HLA A*02:01-restricted WT1126-134 (RMFPNAPYL) epitope were administered in high-risk AML patients after allogeneic hematopoietic stem cell transplantation.
• WT-1 specific T cell delivery was generally well tolerated.
• 13/15 patients remain alive with follow-up for up to 18 months.
•12/15 have ongoing detectable WT-1 cells with follow up ranging from 5 to 368 days from the last infusion.
About Juno’s Chimeric Antigen Receptor and High-affinity T Cell Receptor Platform
Juno is developing cell-based immunotherapies based on its chimeric antigen receptor, or CAR, and high-affinity T cell receptor, or TCR, platform to genetically engineer T cells to recognize and kill cancer cells. T cells are a type of white blood cells that identify and kill infected or abnormal cells, including cancer cells, in healthy individuals. Juno leverages its CAR and TCR platform to activate a patient’s own T cells so that they attack cancer cells. Through genetic engineering, a gene is inserted for a particular CAR or TCR construct into the T cell enabling it to better recognize cancer cells. The CAR technology directs T cells to recognize cancer cells based on the expression of specific proteins located on the cell surface, whereas the 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. CAR constructs typically use a single chain variable fragment, or scFv, to recognize a protein of interest. The modified T cells can be infused into the patient or frozen and stored for later infusion.
About Juno
Juno Therapeutics, Inc. is building a fully integrated biopharmaceutical company focused on revolutionizing medicine by re-engaging the body’s immune system to treat cancer. Founded on the vision that the use of human cells as therapeutic entities will drive one of the next important phases in medicine, Juno is developing cell-based cancer immunotherapies based on chimeric antigen receptor and high-affinity T cell receptor technologies to genetically engineer T cells to recognize and kill cancer. Juno is developing multiple cell-based product candidates to treat a variety of B-cell malignancies as well as solid tumors. Several product candidates have shown compelling evidence of tumor shrinkage in the clinical trials in refractory leukemia and lymphoma conducted to date. The company’s long-term aim is to improve and leverage its cell-based platform to develop new product candidates that address a broader range of cancers and human diseases. Juno brings together innovative technologies from some of the world’s leading research institutions, including the Fred Hutchinson Cancer Research Center, Memorial Sloan Kettering Cancer Center, and Seattle Children’s Research Institute.
www.JunoTherapeutics.com
Forward Looking Statements
This press release contains forward-looking statements, including statements regarding the clinical development of our product candidates, the safety and efficacy of our product candidates as well as their potential, and the encouraging nature of clinical data observed to date. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: risks associated with the success, cost and timing of our product development activities and clinical trials; the approval and commercialization of our product candidates; and risks of increased regulatory requirements, amongst others. These forward-looking statements speak only as of the date hereof. Juno Therapeutics disclaims any obligation to update these forward-looking statements.
Contacts
W2O Group
Investor Relations:
David Walsey, 858-617-0772
dwalsey@w2ogroup.com
or
Media:
Andreas Marathovouniotis, 212-301-7174
amarathis@w2ogroup.com
Help employers find you! Check out all the jobs and post your resume.