Date: 2017-06-07
Type of
information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the International Conference on Malignant Lymphoma (ICML) meeting,
Company: Novartis (Switzerland)
Product: CTL019 - tisagenlecleucel-T
Action
mechanism:
- cell therapy/gene therapy/CAR-T cell therapy. 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. CD19 is associated with a number of B-cell malignancies including ALL, CLL, diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. 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. These autologous T cells transduced with lentiviral vector containing a chimeric antigen receptor directed against CD19 were previously known as CART19.
- In July 2014, the FDA designated CTL019 as a Breakthrough Therapy for the treatment of pediatric and adult patients with r/r ALL under the Penn IND. 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. Oxford BioMedica is the sole manufacturer of the lentiviral vector expressing CTL019 for Novartis. The commercial launch of CTL019 is anticipated by Novartis later this year and Oxford BioMedica will receive undisclosed royalties on potential future sales of Novartis CAR-T products.
Disease: diffuse large B-cell lymphoma (DLBCL)
Therapeutic
area: Cancer - Oncology
Country: Australia, Austria, Canada, France, Germany, Italy, Japan, Netherlands, Norway, USA
Trial
details:
- The JULIET trial is a single-arm, open-label, multi-center global Phase II trial of CTL019 in patients aged 18 years or older with r/r DLBCL. Prior to enrollment, patients were required to have received two or more lines of prior chemotherapy and had disease progression or were ineligible for autologous stem cell transplant (autoSCT). Sixty percent of the patients had three or more lines of chemotherapy and 51% had a prior autoSCT. (NCT02445248)
- JULIET is the first multi-center global registration study for CTL019 in adult patients with r/r DLBCL and the second global CAR-T cell therapy trial, following the Novartis ELIANA study of CTL019 in pediatric and young adult patients with r/r B-cell acute lymphoblastic leukemia (ALL). JULIET was conducted in collaboration with Penn and enrolled patients from 27 sites in 10 countries across the US, Canada, Europe, Australia and Japan. It is the largest study examining a CAR-T cell therapy exclusively in DLBCL patients.
Latest
news:
- • On June 7, 2017, Novartis announced findings from an interim analysis of its multi-center Phase II JULIET study of CTL019 (tisagenlecleucel) in adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL), which will be presented at the International Conference on Malignant Lymphoma (ICML) meeting, Lugano, Switzerland.
- The global, pivotal study showed a three-month overall response rate (ORR) of 45% (23 of the 51 patients evaluated), with 37% achieving a complete response (CR) and 8% achieving a partial response (PR), respectively. CR remained stable from three months through data cutoff among the patient group.
- The study met its primary objective at interim analysis. Among 51 patients with three months or more of follow-up or earlier discontinuation, best ORR was 59% (95% CI, 44.2-72.4; p<0.0001), with 43% achieving CR and 16% achieving PR. The full JULIET primary analysis is expected to be available later this year and will serve as the basis for US and EU regulatory submissions.
- In the JULIET study, 57% of all treated patients (85) experienced any grade cytokine release syndrome (CRS), and 26% experienced grade 3/4 CRS (17% grade 3; 9% grade 4) using the Penn Grading Scale, a rigorous scale for grading CRS. CRS is a known complication of the investigational therapy that may occur when the engineered cells become activated in the patient's body. CRS was managed globally using prior site education on implementation of the CRS treatment algorithm.
- There were no deaths attributed to CTL019, CRS or cerebral edema, and no incidents of cerebral edema were reported in the study. Thirteen percent of patients had grade 3/4 neurologic adverse events, which were managed with supportive care. Grade 3/4 cytopenias lasting more than 28 days and grade 3/4 febrile neutropenia occurred in 21% and 14% of patients, respectively. Three patients died from disease progression within 30 days of infusion.
- In the JULIET trial, 43 patients discontinued before infusion and the majority did so due to rapid progression of their disease or deterioration in their clinical status. This reflects the acute and progressive nature of the disease of the patients. Only nine of 141 (6%) enrolled patients could not be infused due to inability to manufacture an adequate dose of CAR-T cells. Over the course of JULIET, with continuous process improvements, manufacturing success rate improved to 97% for the last 30 patients.
- • On May 5, 2015, a Phase 2 trial (JULIET) sponsored by Novartis was published on the NIH website ClinicalTrials.gov for CTL019 and is currently recruiting participants.
Is
general: Yes
