Data from the pivotal Phase 1b/2 FELIX study of obecabtagene autoleucel (obe-cel) in relapsed/refractory (r/r) adult B-cell Acute Lymphoblastic Leukemia (ALL) has been published in The New England Journal of Medicine, demonstrating high rates of durable responses with a low incidence of severe immune-related toxicity.
The study, led by Dr. Claire Roddie from University College London (UCL) Cancer Institute and Dr. Elias Jabbour from The University of Texas MD Anderson Cancer Center, evaluated obe-cel in adult patients with r/r B-ALL. Results showed a 76.6% overall response rate (CR/CRi) in the pivotal cohort of patients who received at least one infusion of obe-cel, with a median follow-up of 20.3 months.
Key Findings from the FELIX Study
The FELIX trial enrolled 153 r/r B-ALL patients, with 127 receiving at least one obe-cel infusion. The primary endpoint, overall remission (CR/CRi), was achieved in 76.6% of patients in the pivotal cohort (n=94). Among all infused patients (n=127) with ≥5% bone marrow (BM) blasts pre-lymphodepletion, the CR/CRi was 74.7%.
Median response duration for all infused patients was 21.2 months. The median event-free survival (EFS) was 11.9 months, with estimated 6- and 12-month event-free survival rates of 65.4% and 49.5%, respectively. Bone marrow burden pre-lymphodepletion correlated with median event-free survival; patients with low (<5% BM blasts), intermediate (≥5–≤75% blasts), and high (>75% blasts) BM burden had event-free survival rates at 12 months of 68.0%, 54.9% and 25.0%, respectively.
Median overall survival (OS) was 15.6 months, and estimated 6- and 12-month overall survival rates were 80.3% and 61.1%, respectively. Bone marrow burden pre-lymphodepletion correlated with overall survival; patients with low, intermediate, and high BM burden had an overall survival rate at 12 months of 71.5%, 58.7% and 55.0%, respectively.
Safety Profile and Toxicity
Obe-cel was associated with minimal immunotoxicity. Grade ≥3 Cytokine Release Syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) rates were 2.4% and 7.1%, respectively. Overall, 68.5% of patients developed CRS, and 22.8% developed ICANS. Severe ICANS post-obe-cel were largely limited to patients with high BM burden pre-lymphodepletion.
Clinical Implications and Future Directions
"With its low rates of serious side effects coupled with compelling long-term survival data and durable responses, obe-cel offers real hope for adult lymphoblastic leukemia patients," said Dr. Claire Roddie. Dr. Roddie also noted the potential for using obe-cel as an earlier-line consolidation therapy, particularly in patients with low-intermediate bone marrow burden who did not receive consolidative allo-Stem Cell Transplant.
Dr. Elias Jabbour added, "The clinical benefit and improvements in survival demonstrated by obe-cel have the potential to redefine the standard of care in the adult relapsed/refractory B-ALL setting."
Regulatory Status
Obe-cel was approved by the Food & Drug Administration (FDA) under the brand name AUCATZYL® (obecabtagene autoleucel) on November 8, 2024. Marketing authorization applications (MAAs) for obe-cel are under review by regulators in both the EU and the UK, with submissions accepted by the European Medicines Agency (EMA) in March 2024 and by the UK MHRA in August 2024.
About the FELIX Trial
The Phase 1b/2 FELIX clinical trial of obe-cel enrolled adult patients with r/r B-precursor ALL across 30 leading academic and non-academic centers in the United States, United Kingdom, and Europe. The primary endpoint was overall response rate, with secondary endpoints including duration of response, MRD negative complete remission rate, and safety.
