Obecabtagene autoleucel, sold under the brand name Aucatzyl, is an anti-cancer medication used for the treatment of acute lymphoblastic leukemia.
It is a CD19-directed genetically modified autologous T-cell immunotherapy.
It is indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia.
Obecabtagene autoleucel, or obe-cel approved for the treatment of relapsed or refractory adult B-cell acute lymphoblastic leukemia (ALL).
It is a CD19 directed genetically modified autologous T cell immunotherapy composed of autologous T cells, transduced with a lentiviral vector to express an anti-CD chimeric antigen receptor (CAR).
Approval of the CD19 chimeric antigen receptor T-cell therapy (CAR T) — designed to have a ‘fast-off’ kinetic” to minimize excessive activation of the programmed T cells and thereby increase T-cell persistence and reduce T-cell exhaustion.
FELIX study: The pooled analysis showed a complete response (CR) or CR with incomplete hematologic recovery (CR/CRi) rate of 77% and a CR rate of 57% at a median follow up of 11 months in 124 patients for treatment of relapsed or refractory adult B-cell acute lymphoblastic leukemia (ALL), at a median follow up of 11 months.
Among evaluable patients, 96% achieved minimal residual disease (MRD)-negative status.
Median duration of response was not reached.
Safety findings showed a low 2.4% and 7.1% rate of grade 3 or higher cytokine release syndrome (CRS) and/or grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS), respectively.
Patients underwent lymphodepletion with fludarabine as 4 x 30 mg/m2 and cyclophosphamide at 2 x 500 mg/m2.
Obe-cel was administered at a target dose of 410 x 106 CAR T cells as a split dose on days 1 and 10 based on pre-lymphodepletion bone marrow blast burden.
CAR T expansion was similar across the study cohorts, and CAR T persistence was ongoing in most responders at follow up.
A particular benefit was observed in patients’ low leukemia burden, defined as morphological remission per investigator assessment (less than 5% bone marrow blasts without extramedullary disease) as measured at screening or at the start of lymphodepletion, prior to obe-cel infusion.
The most common side effects include cytokine release syndrome, infections-pathogen unspecified, musculoskeletal pain, viral infections, fever, nausea, bacterial infectious disorders, diarrhea, febrile neutropenia, immune effector cell-associated neurotoxicity syndrome, hypotension, pain, fatigue, headache, encephalopathy, and hemorrhage.
It has a boxed warning for cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and T-cell malignancies.
Efficacy was evaluated in FELIX an open-label, multicenter, single-arm trial that enrolled adults with relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia.
Enrolled participants were required to have relapsed following a remission lasting twelve months or less, relapsed or refractory acute lymphoblastic leukemia following two or more prior lines of systemic therapy, or disease that was relapsed or refractory three or more months after allogeneic stem cell transplantation.
The major efficacy outcome measures were rate and duration of complete remission achieved within three months after infusion.
Additional outcome measures were rate and duration of overall complete remission which includes complete remission and complete remission with incomplete hematologic recovery, at any time.
Of the 65 participants evaluable for efficacy, 27 participants (42%) achieved complete remission within three months.
The median duration of complete remission achieved within three months was 14.1 months (95% CI: 6.1, not reached).
Obe-cel CAR treatment resulted in a high incidence of durable response among patients with relapsed or refractory B-cell ALL with a low incidence of grade 3 or higher immune related toxic effects.