FELIX Study Assesses Tumor Burden-Guided Dosing of Obe-Cel in B-Cell ALL

Obecabtagene autoleucel (obe-cel) is effective for the treatment of relapsed or refractory adult B-cell acute lymphoblastic leukemia (B-cell ALL), according to the phase Ib/II FELIX trial presented at the Society of Hematologic Oncology 2024 Annual Meeting in Houston, Texas.

Obe-cel is a novel autologous chimeric antigen receptor (CAR) T-cell therapy designed to improve persistence and immunotoxicity. In FELIX, patients with relapsed or refractory B-cell ALL received obe-cel as tumor burden (TB)-guided infusions based on bone marrow (BM) blast percentage prior to lymphodepletion.

The study included 127 patients who were infused with obe-cel on days 1 and 10, to a target dose of 410×10⁶ CAR T cells. For those with low TB (defined as ≤20% BM blasts at lymphodepletion), dose 1 was 100×10⁶ and dose 2 was 310×10⁶. For the high TB group (>20% BM blasts at lymphodepletion), dose 1 was 10×10⁶ and dose 2 was 400×10⁶. Overall, 120 (94%) patients received the two doses as planned.

The investigators reported high CAR-T expansion that progressively increased with TB. Over 28 days in both the low and high TB groups, peak expansion was reached after dose 2—day 15 in the low TB group and day 11 in the high TB group. The overall remission rates were 90% and 75% in the low and high TB groups, respectively. The investigators noted that patients demonstrated low peak cytokines despite high CAR T-cell expansion.

TB-guided dosing led to a manageable adverse event (AE) profile in both groups. There were 52 and 75 grade ≥3 AEs in the low and high TB groups, respectively. Rates of grade ≥3 cytokine release syndrome were 1.9% and 2.7%, respectively. Immune effector cell–associated neurotoxicity syndrome at grade ≥3 occurred in 3.8% of the low TB group and 9.3% of the high TB group. The use of tocilizumab and steroids to manage AEs did not affect CAR T-cell expansion or persistence, the authors noted.

“Obe-cel’s unique fast off-rate binder, administered using the TB-guided dosing strategy, resulted in substantial efficacy while protecting patients against onset of immunotoxicity,” the authors wrote. “This supports the TB-guided dosing approach in adult [relapsed or refractory B-cell ALL].”

Reference

Jabbour E, Sandhu KS, Shaughnessy P, et al. Obecabtagene autoleucel (obe-cel) for relapsed/refractory adult B-cell acute lymphoblastic leukemia (R/R B-ALL): impact of chimeric antigen receptor T-cell (CAR T) and tumor burden–guided dosing in the FELIX phase 1b/2 study. Abstract #ALL-502. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; Sept. 4-7, 2024; Houston, Texas.