— Promising complete response rates demonstrated in NHL and CLL —
— Clinical responses correlate with cell expansion and persistence —
SEATTLE, WA, USA I December 6, 2015 I Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer, today announced, in partnership with its collaborators, that clinical data from a chimeric antigen receptor (CAR) T cell product candidate, JCAR014, demonstrated encouraging clinical responses in patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Results will be presented in an oral presentation today at the 54th Annual Meeting of the American Society of Hematology (ASH) in Orlando.
In addition, a poster presentation highlighted clinical data from JCAR018, a CAR T cell product candidate targeting CD22 that demonstrated preliminary safety and clinical activity in pediatric and young adult r/r B-cell acute lymphoblastic leukemia (ALL) patients.
“Complete responses and the durability of those responses are key efficacy parameters in both NHL and CLL. The early data reported today are highly encouraging and suggest that our CD19-directed CAR T product candidates have the potential to have a meaningful impact for patients with these difficult-to-treat diseases,” said Mark Frohlich, M.D., Executive Vice President, Development and Portfolio Strategy. “Our CD22-directed CAR T product candidate, JCAR018, has shown encouraging early signs of activity from the study in pediatric patients with r/r ALL, where CD19 epitope loss with treatment appears to be of increasing relevance. We look forward to more data in 2016 as we continue to treat patients at the current and higher dose levels.”
In an oral presentation on Sunday, December 6, 2015, Cameron J. Turtle, MBBS, Ph.D. of the Fred Hutchinson Cancer Research Center will present “Anti-CD19 Chimeric Antigen Receptor-Modified T Cell Therapy for B Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Fludarabine and Cyclophosphamide Lymphodepletion Improves In Vivo Expansion and Persistence of CAR T Cells and Clinical Outcomes.” Dr. Turtle will be updating results on a total of 41 patients treated with JCAR014 against B-cell malignancies. Key data will include:
| |
| NHL Results: Regimens & Doses |
| Conditioning Regimen |
|
Non-Flu/Cy |
|
Flu/Cy |
|
|
|
|
| Dose Level |
|
All Doses
N=12 |
|
2*105/kg
N=3 |
|
2*106/kg(1)
N=11 |
|
2*107/kg
N=4 |
| |
|
|
|
|
|
|
|
|
| Efficacy |
|
|
|
|
|
|
|
|
| CR |
|
1/12
(8%) |
|
1/3
(33%) |
|
7/11
(64%) |
|
1/4
(25%) |
| |
|
|
|
|
|
|
|
|
| CR/PR |
|
6/12
(50%) |
|
1/3
(33%) |
|
9/11
(82%) |
|
3/4
(75%) |
| |
|
|
|
|
|
|
|
|
| Toxicity |
|
|
|
|
|
|
|
|
| Severe Cytokine Release Syndrome |
|
0/12
(0%) |
|
0/3
(0%) |
|
1/11
(9%) |
|
3/6
(50%) |
| Severe Neurotoxicity(1) |
|
2/12
(17%) |
|
1/3
(33%) |
|
2/11
(18%) |
|
4/6
(67%) |
(1)The 2*106/kg dose highlighted in the box above represents the dose moving forward.
(2)All patients in the Flu/Cy cohorts that achieved a CR remain in CR 2-9 months after therapy.
CR = complete response; PR = partial response
Median of 5 prior treatment regimens; 16 patients failed prior autologous and/or allogeneic transplant.
29 out of 32 patients had chemorefractory disease.
| |
| CLL Results: Regimens & Doses |
| Conditioning Regimen |
|
Non-Flu/Cy(1) |
|
Flu/Cy(1,2) |
| Dose Level |
|
All Doses
N=2 |
|
All Doses
N=7 |
| |
|
|
|
|
| Efficacy |
|
|
|
|
| CR(2) |
|
0/2
(0%) |
|
4/7
(57%) |
| |
|
|
|
|
| CR/PR(3) |
|
1/2
(50%) |
|
7/7
(100%) |
| |
|
|
|
|
| Toxicity |
|
|
|
|
| Severe Cytokine Release Syndrome |
|
0/2
(0%) |
|
1/7(4)
(14%) |
| Severe Neurotoxicity |
|
0/2
(0%) |
|
3/7
(43%) |
(1)All CLL patients have been previously treated with ibrutinib.
(2)The flu/cy regimen highlighted in the box represents the conditioning regimen moving forward.
(3)All patients in CR remain in CR 2-14 months after therapy.
(4)The patient died 3 months after therapy of pulmonary aspergillosis.
Key Takeaways include:
- JCAR014 (CD19-specific CAR T cells of defined subset composition) demonstrated potent anti-tumor activity and an acceptable toxicity profile in r/r adult B-cell NHL patients and CLL patients previously treated with ibrutinib.
- A meaningful percentage of patients achieved a complete response in both r/r NHL and r/r CLL.
- While longer follow-up is necessary to define full durability, there have been no relapses in NHL and CLL patients that achieved a complete response in this study with follow-up ranging from 2 to 14 months.
- The addition of fludarabine and cyclophosphamide (flu/cy) lymphodepletion improved CAR T cell peak expansion, persistence and clinical outcomes in NHL.
- Severe cytokine release syndrome and severe neurotoxicity were observed in some patients; lower doses of this defined cell product candidate appeared to correlate with lower rates of these toxicities.
In a poster presentation on Saturday, December 5, 2015, Terry J. Fry, M.D. of the Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, presented “Clinical Activity and Persistence of Anti-CD22 Chimeric Antigen Receptor in Children and Young Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL).” Dr. Fry reported on a first-in-human anti-CD22 CAR T cell therapy (JCAR018) in pediatric and young adult r/r B-cell ALL. Key takeaways include:
- JCAR018 provides a potential treatment alternative to patients with CD19 epitope loss variants, particularly relevant in pediatric ALL.
- In this Phase I dose-escalation trial, nine patients have enrolled and seven patients have been assessed to date.
- Six patients were treated with the lowest dose (3 x 105 cells/kg), with one patient reaching MRD-negative CR, two patients having stable disease, and three patients having disease progression.
- Three patients have enrolled at the next dose (1 x 106 cells/kg), which is in the dose range of CD19-directed CAR T programs. One patient achieved an MRD-negative CR, and two patients are too early to assess for response.
- One patient at the lowest dose had Grade 3 diarrhea, and the maximum cytokine release syndrome was Grade 2.
ASH Investor and Analyst Event and Webcast
The Juno ASH Investor and Analyst Event and webcast will be held Monday, December 7, 2015 at 8:30p.m. Eastern Time. The webcast can be accessed live on the Investor Relations page of Juno’s website, www.JunoTherapeutics.com, and will be available for replay for 30 days following the event.
About Juno’s Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR) Technologies
Juno’s chimeric antigen receptor (CAR) and T cell receptor technologies (TCR) 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.
About Juno
Juno Therapeutics 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 clinical trials in refractory leukemia and lymphoma conducted to date. Juno’s long-term aim is to 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, Seattle Children’s Research Institute, and The National Cancer Institute. Juno Therapeutics has an exclusive license to the St. Jude Children’s Research Hospital patented technology for CD19 directed product candidates that use 4-1BB, which was developed by Dario Campana, Chihaya Imai, and St. Jude Children’s Research Hospital.
SOURCE: Juno Therapeutics
Post Views: 83
— Promising complete response rates demonstrated in NHL and CLL —
— Clinical responses correlate with cell expansion and persistence —
SEATTLE, WA, USA I December 6, 2015 I Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer, today announced, in partnership with its collaborators, that clinical data from a chimeric antigen receptor (CAR) T cell product candidate, JCAR014, demonstrated encouraging clinical responses in patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Results will be presented in an oral presentation today at the 54th Annual Meeting of the American Society of Hematology (ASH) in Orlando.
In addition, a poster presentation highlighted clinical data from JCAR018, a CAR T cell product candidate targeting CD22 that demonstrated preliminary safety and clinical activity in pediatric and young adult r/r B-cell acute lymphoblastic leukemia (ALL) patients.
“Complete responses and the durability of those responses are key efficacy parameters in both NHL and CLL. The early data reported today are highly encouraging and suggest that our CD19-directed CAR T product candidates have the potential to have a meaningful impact for patients with these difficult-to-treat diseases,” said Mark Frohlich, M.D., Executive Vice President, Development and Portfolio Strategy. “Our CD22-directed CAR T product candidate, JCAR018, has shown encouraging early signs of activity from the study in pediatric patients with r/r ALL, where CD19 epitope loss with treatment appears to be of increasing relevance. We look forward to more data in 2016 as we continue to treat patients at the current and higher dose levels.”
In an oral presentation on Sunday, December 6, 2015, Cameron J. Turtle, MBBS, Ph.D. of the Fred Hutchinson Cancer Research Center will present “Anti-CD19 Chimeric Antigen Receptor-Modified T Cell Therapy for B Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Fludarabine and Cyclophosphamide Lymphodepletion Improves In Vivo Expansion and Persistence of CAR T Cells and Clinical Outcomes.” Dr. Turtle will be updating results on a total of 41 patients treated with JCAR014 against B-cell malignancies. Key data will include:
| |
| NHL Results: Regimens & Doses |
| Conditioning Regimen |
|
Non-Flu/Cy |
|
Flu/Cy |
|
|
|
|
| Dose Level |
|
All Doses
N=12 |
|
2*105/kg
N=3 |
|
2*106/kg(1)
N=11 |
|
2*107/kg
N=4 |
| |
|
|
|
|
|
|
|
|
| Efficacy |
|
|
|
|
|
|
|
|
| CR |
|
1/12
(8%) |
|
1/3
(33%) |
|
7/11
(64%) |
|
1/4
(25%) |
| |
|
|
|
|
|
|
|
|
| CR/PR |
|
6/12
(50%) |
|
1/3
(33%) |
|
9/11
(82%) |
|
3/4
(75%) |
| |
|
|
|
|
|
|
|
|
| Toxicity |
|
|
|
|
|
|
|
|
| Severe Cytokine Release Syndrome |
|
0/12
(0%) |
|
0/3
(0%) |
|
1/11
(9%) |
|
3/6
(50%) |
| Severe Neurotoxicity(1) |
|
2/12
(17%) |
|
1/3
(33%) |
|
2/11
(18%) |
|
4/6
(67%) |
(1)The 2*106/kg dose highlighted in the box above represents the dose moving forward.
(2)All patients in the Flu/Cy cohorts that achieved a CR remain in CR 2-9 months after therapy.
CR = complete response; PR = partial response
Median of 5 prior treatment regimens; 16 patients failed prior autologous and/or allogeneic transplant.
29 out of 32 patients had chemorefractory disease.
| |
| CLL Results: Regimens & Doses |
| Conditioning Regimen |
|
Non-Flu/Cy(1) |
|
Flu/Cy(1,2) |
| Dose Level |
|
All Doses
N=2 |
|
All Doses
N=7 |
| |
|
|
|
|
| Efficacy |
|
|
|
|
| CR(2) |
|
0/2
(0%) |
|
4/7
(57%) |
| |
|
|
|
|
| CR/PR(3) |
|
1/2
(50%) |
|
7/7
(100%) |
| |
|
|
|
|
| Toxicity |
|
|
|
|
| Severe Cytokine Release Syndrome |
|
0/2
(0%) |
|
1/7(4)
(14%) |
| Severe Neurotoxicity |
|
0/2
(0%) |
|
3/7
(43%) |
(1)All CLL patients have been previously treated with ibrutinib.
(2)The flu/cy regimen highlighted in the box represents the conditioning regimen moving forward.
(3)All patients in CR remain in CR 2-14 months after therapy.
(4)The patient died 3 months after therapy of pulmonary aspergillosis.
Key Takeaways include:
- JCAR014 (CD19-specific CAR T cells of defined subset composition) demonstrated potent anti-tumor activity and an acceptable toxicity profile in r/r adult B-cell NHL patients and CLL patients previously treated with ibrutinib.
- A meaningful percentage of patients achieved a complete response in both r/r NHL and r/r CLL.
- While longer follow-up is necessary to define full durability, there have been no relapses in NHL and CLL patients that achieved a complete response in this study with follow-up ranging from 2 to 14 months.
- The addition of fludarabine and cyclophosphamide (flu/cy) lymphodepletion improved CAR T cell peak expansion, persistence and clinical outcomes in NHL.
- Severe cytokine release syndrome and severe neurotoxicity were observed in some patients; lower doses of this defined cell product candidate appeared to correlate with lower rates of these toxicities.
In a poster presentation on Saturday, December 5, 2015, Terry J. Fry, M.D. of the Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, presented “Clinical Activity and Persistence of Anti-CD22 Chimeric Antigen Receptor in Children and Young Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL).” Dr. Fry reported on a first-in-human anti-CD22 CAR T cell therapy (JCAR018) in pediatric and young adult r/r B-cell ALL. Key takeaways include:
- JCAR018 provides a potential treatment alternative to patients with CD19 epitope loss variants, particularly relevant in pediatric ALL.
- In this Phase I dose-escalation trial, nine patients have enrolled and seven patients have been assessed to date.
- Six patients were treated with the lowest dose (3 x 105 cells/kg), with one patient reaching MRD-negative CR, two patients having stable disease, and three patients having disease progression.
- Three patients have enrolled at the next dose (1 x 106 cells/kg), which is in the dose range of CD19-directed CAR T programs. One patient achieved an MRD-negative CR, and two patients are too early to assess for response.
- One patient at the lowest dose had Grade 3 diarrhea, and the maximum cytokine release syndrome was Grade 2.
ASH Investor and Analyst Event and Webcast
The Juno ASH Investor and Analyst Event and webcast will be held Monday, December 7, 2015 at 8:30p.m. Eastern Time. The webcast can be accessed live on the Investor Relations page of Juno’s website, www.JunoTherapeutics.com, and will be available for replay for 30 days following the event.
About Juno’s Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR) Technologies
Juno’s chimeric antigen receptor (CAR) and T cell receptor technologies (TCR) 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.
About Juno
Juno Therapeutics 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 clinical trials in refractory leukemia and lymphoma conducted to date. Juno’s long-term aim is to 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, Seattle Children’s Research Institute, and The National Cancer Institute. Juno Therapeutics has an exclusive license to the St. Jude Children’s Research Hospital patented technology for CD19 directed product candidates that use 4-1BB, which was developed by Dario Campana, Chihaya Imai, and St. Jude Children’s Research Hospital.
SOURCE: Juno Therapeutics
Post Views: 83
