FELIX phase Ib/II: Tumor burden-guided obe-cel in R/R B-ALL

The open-label, multicenter, global, single-arm, phase Ib/II FELIX trial (NCT04404660) is investigating obecabtagene autoleucel (obe-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy with tumor burden-guided dosing, in 127 adults with CD19+ relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Results were published in Haematologica by Jabbour et al. Patients received split-dose infusions based on pre-lymphodepletion bone marrow (BM) blast percentage: ≤20% (low tumor burden [TB]) or >20% (high-TB), with all patients receiving a total target dose of 410 × 10⁶ CAR T-cells.

Key data: Tumor burden at lymphodepletion was a critical driver of CAR T-cell expansion, with a 50% increase in BM blasts associated with a 1.9-fold increase in maximal CAR T-cell expansion (95% confidence interval [CI], 1.4–2.6). Despite higher expansion in the high-TB group, Grade ≥3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) incidence remained low in both groups (low-TB: 2% and 4%; high-TB: 3% and 9%, respectively). At a median follow-up of 21.5 months, complete remission (CR) / CR with incomplete hematologic recovery (CRi) rate per independent review committee (IRC) was 85% (95% CI, 72–93) in the low-TB group and 73% (95% CI, 62–83) in the high-TB group.

Key learning: Tumor burden-guided dosing of obe-cel successfully mitigated severe immunotoxicities typically associated with high tumor burden in adult R/R B-ALL while maintaining efficacy across both tumor burden groups, supporting this dosing strategy as a practical approach to improve the safety profile of CAR T-cell therapy.