- Eight of nine evaluable patients tested had no signs of CLL in their bone marrow at three months.
- CTL119 is a humanized CD19-directed CAR-T cell therapy being developed in collaboration with the University of Pennsylvania
- Novartis is committed to advancing a portfolio of next-generation CAR-T cell therapies
BASEL, Switzerland I May 30, 2017 I Novartis announced findings from a pilot study (NCT02640209) of CTL119 in combination with ibrutinib* in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who had been taking ibrutinib for at least six months and who were not in complete remission. All study patients had to have failed at least one prior regimen before ibrutinib or carried high-risk cytogenetics or mutations. The results, which will be presented at the upcoming 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO; abstract #7509; Monday, June 5, 1:15 PM CDT), that eight of nine evaluable patients had no signs of CLL in their bone marrow at three months. One of those patients had a partial response [1].
“The data from this pilot study support the potential for CTL119, when combined with the kinase inhibitor ibrutinib, to induce clinically-significant responses in high-risk CLL patients who were unlikely to achieve a complete remission on ibrutinib alone,” said James Bradner, president of the Novartis Institutes for BioMedical Research. “CTL119 represents one of our latest advances in CAR-T cell therapy research and our broader commitment to pioneering breakthrough immuno-oncology treatments.”
The findings will be presented by Saar Gill, MD, PhD, an assistant professor of Hematology-Oncology in the Perelman School of Medicine and the Abramson Cancer Center of the University of Pennsylvania.
CTL119 is a humanized CD19-directed chimeric antigen receptor T cell (CAR-T) cell therapy, which is different from typical small molecule or biologic therapies because it is manufactured for each individual patient using their own cells. During the treatment process, T cells are drawn from a patient’s blood and reprogrammed in the laboratory to create T cells that are genetically coded to hunt the patient’s cancer cells and other B-cells expressing a particular antigen.
Results from the pilot study also showed that eight of nine patients had no signs of CLL in their bone marrow at three months as tested by flow cytometry and/or analysis for minimal residual disease (MRD)[1]. MRD, which measures the presence of residual abnormalities in the blood and bone marrow at the molecular level following treatment, is important because it can be an indicator of potential relapse[2].
CT scans were performed to measure the inclusion of CLL in the spleens and lymph nodes of study patients. A number of patients showed improvements in the burden of disease in their spleens and lymph nodes at three months, though radiologic responses are less clear cut and they require longer follow-up[1].
In the study, 10 patients experienced cytokine release syndrome (CRS), two of which were grade 3. However, no patients required treatment with tocilizumab** and all patients recovered from CRS. One patient developed tumor lysis syndrome and two patients had febrile neutropenia [1].
CLL is one of the most common types of adult leukemia, which typically progresses slowly over time[3]. The majority of patients will relapse after initial therapy[4], and newer targeted therapies must be taken continuously for an indefinite period of time[5]. These are clear indications of the high unmet medical need for new therapies for CLL.
About the Novartis CAR-T Program
In 2012, Novartis and the University of Pennsylvania entered into a global collaboration to further research, develop and then commercialize CAR-T cell therapies for the investigational treatment of cancers. In March 2017, Novartis announced that the US Food and Drug Administration (FDA) accepted the company’s Biologics License Application filing and granted priority review for CTL019 in the treatment of relapsed/refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia. In April 2017, FDA granted Breakthrough Therapy designation to CTL019 for relapsed/refractory diffuse large B-cell lymphoma.
During the collaboration between Novartis and the University of Pennsylvania, researchers generated the humanized anti-CD19 CAR, CTL119. CTL119 is in initial clinical development for multiple B-cell malignancies. Because CTL119 and CTL019 are investigational therapies, the safety and efficacy profile has not yet been established. Access to investigational therapies is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the therapy. Because of the uncertainty of clinical trials, there is no guarantee that CTL119 or CTL019 will become commercially available.
Notes
* Ibrutinib is marketed as IMBRUVICA®, a registered trademark owned by Pharmacyclics LLC.
** Tocilizumab is marketed as ACTEMRA®, which is a registered trademark of Chugai Seiyaku Kabushiki Kaisha Corp., a member of the Roche Group.
About Novartis
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2016, the Group achieved net sales of USD 48.5 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com.
Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartis and @NovartisScience at http://twitter.com/novartisscience
For Novartis multimedia content, please visit www.novartis.com/news/media-library
For questions about the site or required registration, please contact media.relations@novartis.com
| References |
| [1] |
Gill S, Frey N, et al. Anti-CD19 CART cells combined with ibrutinib induce a high rate of remission in CLL. June 5, 1:15 PM CDT. 53rd Annual Meeting of the American Society of Clinical Oncology. |
| [2] |
Campana, Dario. Minimal Residual Disease in Acute Lymphoblastic Leukemia. Seminars in hematology 46.1 (2009): 100-106. PMC. Web. 22 May 2017. |
| [3] |
National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ®)-Patient Version. Available at https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq. Accessed May 2017. |
| [4] |
Veliz M, Pinilla-Ibarz J. Treatment of relapsed or refractory chronic lymphocytic leukemia. Cancer Control. 2012; 1:37-53 |
| [5] |
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia. Version 2.2017. 21 February 2017. |
SOURCE: Novartis
Post Views: 29
- Eight of nine evaluable patients tested had no signs of CLL in their bone marrow at three months.
- CTL119 is a humanized CD19-directed CAR-T cell therapy being developed in collaboration with the University of Pennsylvania
- Novartis is committed to advancing a portfolio of next-generation CAR-T cell therapies
BASEL, Switzerland I May 30, 2017 I Novartis announced findings from a pilot study (NCT02640209) of CTL119 in combination with ibrutinib* in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who had been taking ibrutinib for at least six months and who were not in complete remission. All study patients had to have failed at least one prior regimen before ibrutinib or carried high-risk cytogenetics or mutations. The results, which will be presented at the upcoming 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO; abstract #7509; Monday, June 5, 1:15 PM CDT), that eight of nine evaluable patients had no signs of CLL in their bone marrow at three months. One of those patients had a partial response [1].
“The data from this pilot study support the potential for CTL119, when combined with the kinase inhibitor ibrutinib, to induce clinically-significant responses in high-risk CLL patients who were unlikely to achieve a complete remission on ibrutinib alone,” said James Bradner, president of the Novartis Institutes for BioMedical Research. “CTL119 represents one of our latest advances in CAR-T cell therapy research and our broader commitment to pioneering breakthrough immuno-oncology treatments.”
The findings will be presented by Saar Gill, MD, PhD, an assistant professor of Hematology-Oncology in the Perelman School of Medicine and the Abramson Cancer Center of the University of Pennsylvania.
CTL119 is a humanized CD19-directed chimeric antigen receptor T cell (CAR-T) cell therapy, which is different from typical small molecule or biologic therapies because it is manufactured for each individual patient using their own cells. During the treatment process, T cells are drawn from a patient’s blood and reprogrammed in the laboratory to create T cells that are genetically coded to hunt the patient’s cancer cells and other B-cells expressing a particular antigen.
Results from the pilot study also showed that eight of nine patients had no signs of CLL in their bone marrow at three months as tested by flow cytometry and/or analysis for minimal residual disease (MRD)[1]. MRD, which measures the presence of residual abnormalities in the blood and bone marrow at the molecular level following treatment, is important because it can be an indicator of potential relapse[2].
CT scans were performed to measure the inclusion of CLL in the spleens and lymph nodes of study patients. A number of patients showed improvements in the burden of disease in their spleens and lymph nodes at three months, though radiologic responses are less clear cut and they require longer follow-up[1].
In the study, 10 patients experienced cytokine release syndrome (CRS), two of which were grade 3. However, no patients required treatment with tocilizumab** and all patients recovered from CRS. One patient developed tumor lysis syndrome and two patients had febrile neutropenia [1].
CLL is one of the most common types of adult leukemia, which typically progresses slowly over time[3]. The majority of patients will relapse after initial therapy[4], and newer targeted therapies must be taken continuously for an indefinite period of time[5]. These are clear indications of the high unmet medical need for new therapies for CLL.
About the Novartis CAR-T Program
In 2012, Novartis and the University of Pennsylvania entered into a global collaboration to further research, develop and then commercialize CAR-T cell therapies for the investigational treatment of cancers. In March 2017, Novartis announced that the US Food and Drug Administration (FDA) accepted the company’s Biologics License Application filing and granted priority review for CTL019 in the treatment of relapsed/refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia. In April 2017, FDA granted Breakthrough Therapy designation to CTL019 for relapsed/refractory diffuse large B-cell lymphoma.
During the collaboration between Novartis and the University of Pennsylvania, researchers generated the humanized anti-CD19 CAR, CTL119. CTL119 is in initial clinical development for multiple B-cell malignancies. Because CTL119 and CTL019 are investigational therapies, the safety and efficacy profile has not yet been established. Access to investigational therapies is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the therapy. Because of the uncertainty of clinical trials, there is no guarantee that CTL119 or CTL019 will become commercially available.
Notes
* Ibrutinib is marketed as IMBRUVICA®, a registered trademark owned by Pharmacyclics LLC.
** Tocilizumab is marketed as ACTEMRA®, which is a registered trademark of Chugai Seiyaku Kabushiki Kaisha Corp., a member of the Roche Group.
About Novartis
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2016, the Group achieved net sales of USD 48.5 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com.
Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartis and @NovartisScience at http://twitter.com/novartisscience
For Novartis multimedia content, please visit www.novartis.com/news/media-library
For questions about the site or required registration, please contact media.relations@novartis.com
| References |
| [1] |
Gill S, Frey N, et al. Anti-CD19 CART cells combined with ibrutinib induce a high rate of remission in CLL. June 5, 1:15 PM CDT. 53rd Annual Meeting of the American Society of Clinical Oncology. |
| [2] |
Campana, Dario. Minimal Residual Disease in Acute Lymphoblastic Leukemia. Seminars in hematology 46.1 (2009): 100-106. PMC. Web. 22 May 2017. |
| [3] |
National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ®)-Patient Version. Available at https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq. Accessed May 2017. |
| [4] |
Veliz M, Pinilla-Ibarz J. Treatment of relapsed or refractory chronic lymphocytic leukemia. Cancer Control. 2012; 1:37-53 |
| [5] |
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia. Version 2.2017. 21 February 2017. |
SOURCE: Novartis
Post Views: 29
