Novartis is highlighting new research from members of the faculty at the University of Pennsylvania’s Perelman School of Medicine (Penn) on the investigational chimeric antigen receptor (CAR) therapy, CTL019. Several studies being presented at the American Society of Hematology (ASH) annual meeting add to the scientific understanding of CTL019 in the treatment of acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) and build on earlier research findings.
“These data reflect a significant advance in our understanding of the novel, investigational CAR therapy, CTL019, which shows potential for advancing the treatment of patients with ALL and CLL,” said Hervé Hoppenot, President, Novartis Oncology. “We are committed, through our collaboration with Penn, to expand the clinical trials of CTL019 to include as many patients as soon as possible.”
Highlights of the presentations include findings that 19 of 22 pediatric patients with ALL (86%) experienced complete remissions. The first pediatric patient treated with the protocol remains in remission 20 months later. Five pediatric patients have relapsed, including one whose tests revealed new tumor cells that do not express the CD19 protein targeted by the reprogrammed cells. Additionally, all five of the first adult ALL patients treated to date have experienced complete remissions, the longest of which continues six months after treatment. One adult patient subsequently underwent a bone marrow transplant and remains in remission. Another adult patient relapsed after three months with disease that also tested negative for the CD19 protein (abstract #67).
In studies of adult patients with CLL, 15 of 32 adult patients (47%) responded to the therapy, with seven of those experiencing a complete remission of their disease (abstract #4162 and #873). These results are derived from a completed pilot study of 14 CLL patients (abstract #4162) and results to date of the first 18 patients in a Phase II, dose-optimization trial (abstract #873). Separately, investigators observed in vivo expansion of CTL019 cells in all patients who achieved a complete response. This was followed by contraction and, in all but one patient, ongoing stable persistence of the reprogrammed T cells (abstract #163).
Novartis and Penn have an exclusive global agreement to research, develop and commercialize personalized CAR T cell therapies for the treatment of cancers. Novartis holds the worldwide rights to CARs developed through the collaboration for all cancer indications, including the lead program CTL019 (also known as CART19). This innovative collaboration has expanded to include multiple CART programs now in discovery and pre-clinical research phases for both hematological cancers and solid tumors.
“This strong collaboration with Novartis, combined with our exciting new research, has brought us closer to making CTL019 available for children and adults who have no other effective treatment options,” said Carl H. June, M.D., director of Translational Research and professor of Pathology and Laboratory Medicine in the University of Pennsylvania’s Abramson Cancer Center and Perelman School of Medicine. “These CTL019 data at ASH reinforce that CAR therapy has the potential to change the treatment paradigm for those suffering from various types of leukemia.”
CTL019 is an investigational, personalized T cell therapy, which was pioneered by Carl June and his team at Penn. In a CTL019 treatment cycle, immune cells (T cells) are drawn from a patient's blood. Then, using CAR technology, the T cells are reprogrammed to “hunt” cancer cells that express specific proteins, called CD19. When the T cells are re-introduced into the patient's blood, the cells proliferate and bind to the targeted cancer cells and destroy them. CD19 is associated with a number of B-cell malignancies including ALL, CLL, diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma.
Additional ASH CTL019 Study Details