European Medicines Agency Validates Bristol Myers Squibb’s Application for CAR T Cell Therapy Lisocabtagene Maraleucel (liso-cel)
Bristol Myers Squibb (NYSE: BMY) have announced that the European Medicines Agency (EMA) has validated its Marketing Authorization Application (MAA) for lisocabtagene maraleucel (liso-cel), an investigational CD19-directed chimeric antigen receptor (CAR) T cell therapy, for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) and follicular lymphoma grade 3B (FL3B) after at least two prior therapies. Validation of the application confirms the submission is complete and begins the EMA’s centralized review process.
Results from TRANSCEND NHL 001, the largest trial in third-line or greater R/R large B-cell lymphoma (LBCL), and additional data from the TRANSCEND WORLD study were the basis of the liso-cel application. The studies evaluated patients with R/R LBCL and included patients with a broad range of histologies and high-risk disease as well as those who received liso-cel in the outpatient setting.
“With more than 30% of patients diagnosed with diffuse large B-cell lymphoma ultimately relapsing after initial therapy and an expected overall survival of about six months for patients who have had two or more prior therapies, there is a need for new treatments,” said Stanley Frankel, M.D., senior vice president, Cellular Therapy Development, Bristol Myers Squibb.1,2 “The EMA’s validation of our application is a critical step toward bringing liso-cel to patients in Europe.”
The EMA previously granted liso-cel access to the PRIME scheme for the treatment of R/R DLBCL and, more recently, Accelerated Assessment status, reducing the maximum timeframe to 150 days for the EMA’s Committee for Medicinal Products for Human Use (CHMP) to review the application.
Liso-cel is an investigational therapy that is not approved for use in any country.
About TRANSCEND NHL 001
TRANSCEND NHL 001 is an open-label, multicenter, pivotal Phase 1 study to determine the safety, antitumor activity and pharmacokinetics of liso-cel in patients with R/R B-cell NHL, including DLBCL, HGL, PMBCL and Grade 3B FL. Mantle cell lymphoma is investigated in a separate cohort. The primary outcome measures included treatment-related adverse events, dose-limiting toxicities and objective response rate. Key secondary outcome measures included complete response rate, duration of response and progression-free survival. The TRANSCEND program is a broad clinical program evaluating liso-cel in multiple indications and treatment lines.
About TRANSCEND WORLD
TRANSCEND WORLD is a single-arm, multi-cohort, multicenter, Phase 2 study to determine the efficacy and safety of liso-cel in patients with aggressive B-cell non-Hodgkin lymphoma (NHL). The primary outcome measure was overall response rate (ORR). Secondary outcome measures included safety, complete response rate, event-free survival, progression-free survival, overall survival, duration of response, pharmacokinetics and health-related quality of life. The study was conducted in Europe and Japan.
About Large B-cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is a rapidly growing, aggressive disease and the most common form of non-Hodgkin lymphoma (NHL), accounting for one out of every three cases diagnosed.3 More than two-thirds of patients will not respond to or will relapse following second-line treatment.3 For patients who relapse or do not respond to initial therapies, conventional treatment options that provide durable remission are limited and median life expectancy is about six months, leaving a critical need for new therapies.2,4
About Lisocabtagene Maraleucel (liso-cel)
Liso-cel is an investigational chimeric antigen receptor (CAR) T cell therapy designed to target CD19, which is a surface glycoprotein expressed during normal B-cell development and maintained following malignant transformation of B cells. Liso-cel aims to target CD19-expressing cells through a CAR construct that includes an anti-CD19 single-chain variable fragment (scFv) targeting domain for antigen specificity, a transmembrane domain, a 4-1BB costimulatory domain hypothesized to increase T cell proliferation and persistence, and a CD3-zeta T cell activation domain. The defined composition of CAR-positive viable T cells (consisting of CD8 and CD4 components) in liso-cel may reduce CAR T product variability; however, the clinical significance of defined composition is unknown.
Bristol Myers Squibb: Advancing Cancer Research
At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients’ quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.
Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational CAR T cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early- to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering potential new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.