Phase II TRANSCEND FL and Phase I TRANSCEND NHL 001 trial data lead to FDA Priority Review designation for Breyanzi to treat relapsed or refractory follicular lymphoma and mantle cell lymphoma.
The FDA has granted Priority Review to a pair of supplemental Biologics License Applications (sBLA) filed by Bristol Myers Squibb to expand the indications of the chimeric antigen receptor (CAR) T-cell therapy Breyanzi (lisocabtagene maraleucel) to include adults with relapsed or refractory (R/R) follicular lymphoma (FL) and R/R mantle cell lymphoma (MCL) following treatment with a Bruton tyrosine kinase inhibitor (BTKi). The FDA assigned Prescription Drug User Fee Act (PDUFA) goal dates of May 23, 2024, to the sBLA for the R/R FL indication and May 31, 2024, for the R/R MCL indication.1
“Patients living with follicular lymphoma and mantle cell lymphoma often experience cycles of remission and relapse with multiple lines of treatment, and we are committed to delivering innovative treatment solutions to this population,” Anne Kerber, MD, Bristol Myers Squibb senior vice president, head of Late Clinical Development, Hematology, Oncology, Cell Therapy, said in a press release. “Breyanzi offers the potential for durable response, and these filing acceptances in the US and Japan support our commitment to delivering our best-in-class CAR T-cell therapy treatments to as many eligible patients as possible.”1
Breyanzi is a CD19-directed CAR T-cell therapy that is made from a patient’s own T cells. The cells are taken from a patient and genetically reengineered to become CAR T cells, which are subsequently infused back into the patient as a one-time treatment.
The sBLA for Breyanzi to treat R/R FL was based on findings from the single-arm, open-label, global, multicenter, Phase II TRANSCEND FL (NCT04245839) trial. According to Bristol Myers Squibb, this was the largest clinical trial to date that analyzed a CAR T-cell therapy in patients with R/R indolent B cell non-Hodgkin lymphoma, including high-risk second-line FL.
Among evaluable patients with R/R FL administered Breyanzi in the third-line plus setting (n=101), the overall response rate (ORR) was 97% and 94% of patients achieved a complete response (CR). ORR and CR were found to be durable, with median duration of response not reached at a median follow-up of 16.6 months and median progression-free survival (PFS) not reached at a median follow-up of 17.5 months. Further, 12-month PFS was achieved in 80.7% of patients.2
The sBLA for the indication in R/R MCL was based on data from the single-arm, open-label, multicenter, pivotal, Phase I TRANSCEND NHL 001 (NCT02631044) trial. The trial evaluated the safety, pharmacokinetics, and antitumor activity of the CAR T-cell therapy in patients with R/R B-cell NHL, including diffuse large B-cell lymphoma, high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, FL Grade 3B, and MCL.
Investigators enrolled adult patients with R/R disease following two or more prior lines of therapy, including a BTK inhibitor. At a median on-study follow-up of 16.1 months, ORR was 86.5% and 74.3% of patients achieved a CR.2
Based on the findings from TRANSCEND NHL 001, Bristol Myers Squibb filed an sBLA for Breyanzi to treat adults with R/R chronic lymphocytic leukemia or small lymphocytic lymphoma who were previously administered BTKi and B-cell lymphoma 2 inhibitor. That sBLA was also granted Priority Review by the FDA and was assigned a PDUFA date of March 14, 2024.
1. Regulatory Applications Accepted in the U.S. and Japan for Bristol Myers Squibb’s Breyanzi (lisocabtagene maraleucel) in Relapsed or Refractory Follicular Lymphoma (FL) and Relapsed or Refractory Mantle Cell Lymphoma (MCL). Bristol Myers Squibb. News release. January 30, 2024. Accessed January 30, 2024. https://news.bms.com/news/details/2024/Regulatory-Applications-Accepted-in-the-U.S.-and-Japan-for-Bristol-Myers-Squibbs-Breyanzi-lisocabtagene-maraleucel-in-Relapsed-or-Refractory-Follicular-Lymphoma-FL-and-Relapsed-or-Refractory-Mantle-Cell-Lymphoma-MCL/default.aspx
2. Bristol Myers Squibb’s Breyanzi (lisocabtagene maraleucel) Delivers Deep and Durable Responses in Relapsed or Refractory Follicular Lymphoma and Mantle Cell Lymphoma in TRANSCEND Clinical Trials Presented at ICML 2023. Bristol Myers Squibb. News release. June 17, 2023. Accessed January 30, 2024. https://news.bms.com/news/corporate-financial/2023/Bristol-Myers-Squibbs-Breyanzi-lisocabtagene-maraleucel-Delivers-Deep-and-Durable-Responses-in-Relapsed-or-Refractory-Follicular-Lymphoma-and-Mantle-Cell-Lymphoma-in-TRANSCEND-Clinical-Trials-Presented-at-ICML-2023/default.aspx