ASH19: Bristol-Myers Squibb to seek FDA approval of liso-cel after pivotal B-cell lymphoma study hits main goals

Bristol-Myers Squibb announced Saturday that a pivotal Phase I study of lisocabtagene maraleucel, also known as liso-cel, in patients with relapsed/refractory large B-cell lymphomas met its primary and secondary endpoints. Results from the TRANSCEND NHL 001 trial were presented at the American Society of Hematology (ASH) annual meeting.

Stanley Frankel, senior vice president of cellular therapy development at Bristol-Myers Squibb, said the "longer-term results…continue to give us confidence in the clinical profile of liso-cel." The company indicated that based on findings from the trial, it expects to complete the submission of a marketing application to the FDA by the end of the year.

In the study, 344 patients with relapsed/refractory large B-cell lymphomas were leukapheresed, with 269 of these subsequently receiving liso-cel at one of three dose levels. The investigational CD19-directed CAR T-cell therapy comprises a defined composition of purified CD8+ and CD4+ CAR T-cells. Bristol-Myers Squibb noted that in the trial, there were 25 patients that received non-conforming product and there were two instances where the therapy could not be manufactured.

Results showed that among 256 patients evaluable for efficacy, the overall response rate was 73%, with 53% of subjects achieving a complete response (CR). The median duration of response for all patients was not reached at a median follow-up of 12 months, while median progression-free survival (PFS) was 6.8 months and median overall survival (OS) was 21.1 months. Bristol-Myers Squibb added that the median PFS and OS for patients who achieved a CR was not reached, with 65.1% of patients progression free and 85.5% of patients alive at 12 months.

Safety findings from the study showed that among all 269 patients, 79% had grade 3 or higher treatment-emergent adverse events including neutropenia in 60% of subjects, anaemia in 38% of participants and thrombocytopenia in 27% of patients. Meanwhile, cytokine release syndrome (CRS) occurred in 42% of patients, with grade 3 or higher CRS occurring in 2% of subjects. Bristol-Myers Squibb added that neurologic events (NEs) occurred in 30% of patients, with grade 3 or higher NEs seen in 10% of participants.

The drugmaker gained liso-cel, previously known as JCAR017, via its $74-billion purchase of Celgene, which was completed last month. As part of the cash and stock transaction, Celgene shareholders received a contingent value right linked to the achievement of future regulatory milestones, with one of these being FDA approval of liso-cel by December 31 next year.

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