FELIX Analysis Highlights Factors Associated With Sustained Remission With Obe-Cel in R/R Acute Lymphoblastic Leukemia

Findings from a multivariant analysis of the phase 1/2 FELIX trial (NCT04404660) demonstrated that certain patient and disease factors were associated with improved remission rates and prolonger survival in patients with relapsed/refractory acute lymphoblastic leukemia (ALL) treated with obecabtagene autoleucel (obe-cel; Aucatzyl).¹

These data were presented at the 2025 EHA Congress and showed that, at baseline, Philadelphia chromosome (Ph)–positive disease (odds ratio [OR], 6.0; 95% CI, 1.4-26.3), 3 or fewer prior lines of therapy (OR, 3.8; 95% CI, 1.2-12.1), and not being refractory to the last line of therapy (OR, 2.9; 95% CI, 1.1-8.0) were all associated with increased complete response (CR)/CR with incomplete hematologic recovery (CRi) rates.

Additionally, a lower bone marrow blasts percentage (<5% vs ≥75%; HR, 0.3; 95% CI, 0.1-0.6), receipt of prior hematopoietic stem cell transplant (HSCT; HR, 0.5; 95% CI, 0.3-0.8), CAR T-cell persistence (HR, 0.4; 95% CI, 0.2-0.9), and receipt of 3 or fewer prior lines of therapy (HR, 0.5; 95% CI, 0.3-1.0) were all associated with improved event-free survival (EFS).

“These findings support the potential for obe-cel to serve as a definitive treatment without HSCT in a subset of patients,” Jae H. Park, MD, said in a presentation of the data. “However, longer follow-up, further analyses, and external validations are necessary to confirm these outcomes.” Park is the chief of Cellular Therapy Service at Memorial Sloan Kettering Cancer Center in New York, New York.

In November 2024, the FDA approved obe-cel for the treatment of adult patients with relapsed or refractory B-cell precursor ALL, based on prior data from FELIX.²

Long-term data from the study showed that among patients who achieved a CR/CRi (n = 99), the median duration of response (DOR) after censoring for consolidative HSCT was 42.5 months (95% CI, 12.5-not evaluable [NE]).¹ The 12- and 24-month DOR rates were 61.8% (95% CI, 50.1%-71.5%) and 54.1% (95% CI, 42.1%-64.6%), respectively.

The median EFS among evaluable patients (n = 127) while censoring for HSCT was 11.9 months (95% CI, 8.0-NE); the respective 12- and 24-month EFS rates were 50.0% (95% CI, 40.2%-59.0%) and 43.0% (95% CI, 33.2%-52.3%). In this patient population—without censoring for HSCT—the median OS was 17.1 months (95% CI, 12.9-28.8), and the 12- and 24-month OS rates were 61.4% (95% CI, 52.4%-69.3%) and 46.0% (95% CI, 37.1%-54.5%), respectively.

Long-term safety data showed that at a median follow-up of 32.8 months, there were no changes in the rates of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) compared with the analysis conducted at a median follow-up of 21.5 months. The rates of any-grade CRS and ICANS were 69% and 23%, respectively. The respective rates of grade 3 or higher CRS and ICANS were 2% and 7%.

At the 21.5-month analysis, the rates of any-grade infections and malignancies were 78% and 2%, respectively. The grade 3 or higher rates were 52% and 2%, respectively. At the 32.8-month analysis, rates of any-grade and grade 3 infections increased to 81% and 55%, respectively. The rate of any-grade secondary malignancies increased to 4%, although there was no change in grade 3 or higher secondary malignancies.

With longer-term follow-up, new infections included 1 instance each of viral pneumonia, recurrent chest infection, enterocolitis infectious and hospital-acquired pneumonia, and multi-lobular pneumonia. The 2 new secondary malignancies reported with longer-term follow-up included lentigo maligna melanoma and urothelial transitional cell carcinoma, which were both deemed unrelated to obe-cel.

FELIX Overview and Analysis Breakdown

The phase 1/2 study included patients at least 18 years of age with relapsed/refractory ALL. Enrolled participants underwent leukapheresis and received bridging therapy and lymphodepleting chemotherapy during obe-cel manufacturing. Lymphodepletion comprised fludarabine at 30 mg/m² per day for 4 days and cyclophosphamide at 500 mg/m² per day for 2 days.

Obe-cel was dosed based on individual tumor burden, with doses split between days 1 and 10. The target dose was 410 x 10⁶ CAR T cells.

CR/CRi rate and minimal residual disease–negativity rate served as the trial’s primary end points. Secondary end points included DOR, EFS, OS, safety, CAR T-cell expansion, and CAR T-cell persistence.

Among the 127 patients infused with obe-cel, 28 patients did not respond or were not evaluable for response; the CR/CRi rate was 78.0%. At a median follow-up of 21.5 months, 40.4% of patients remained in remission without subsequent HSCT or other therapy; 18.2% of patients underwent HSCT while in remission; 5.1% began a new anticancer therapy; 31.3% of patients experienced relapse; and 5.1% died while in remission without subsequent transplant or therapy. At 32.8 months of follow-up, 38.4% of patients remained in remission without subsequent transplant or therapy, and 7.1% of patients had died in remission without subsequent HSCT or treatment. There were no changes in the rates of patients who underwent HSCT while in remission, patients who started a new anticancer therapy, or patients who relapsed.

The multivariant analyses used univariate analysis–selected baseline characteristics to further ascertain which patients were most likely to experience long-term benefit associated with obe-cel. Baseline characteristics alone were used for the CR/CRi multivariant analysis, and the EFS/OS analysis included baseline characteristics and CAR T-cell persistence after treatment.

In the univariate analysis, characteristics that had a P value of less than 0.1 included an age of 55 years or younger (proportion of trial population, 37.8%); not Hispanic or Latino, or unknown ethnicity (70.1%); Ph-positive disease (28.3%); 3 or fewer prior lines of therapy (85.0%); not being refractory to the last prior line of therapy (48.0%); prior HSCT (44.1%); no prior treatment with inotuzumab ozogamicin (Besponsa; 68.5%); no extramedullary disease at lymphodepletion (78.7%); and a bone marrow blasts percentage of less than 5% at lymphodepletion (28.3%).

References

1. Park JH, Roddie C, Tholouli E, et al. Can CAR T-cell therapy be a definitive treatment for adult R/R B-ALL without transplant? Long-term findings and predictors of sustained remission for obecabtagene autoleucel. Presented at: 2025 EHA Congress; June 12-15, 2025; Milan, Italy. Abstract S113.
2. FDA approves obecabtagene autoleucel for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. FDA. November 8, 2024. Accessed July 14, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-obecabtagene-autoleucel-adults-relapsed-or-refractory-b-cell-precursor-acute