Efficacy and safety of obe-cel in R/R adult B-ALL: Phase II FELIX study

CD19-directed chimeric antigen receptor (CAR) T-cell therapies have revolutionized the treatment landscape for relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL).¹ Obecabtagene autoleucel (obe-cel) is a novel autologous CD19 CAR T-cell therapy with a fast off-rate CD19 binding domain designed to improve persistence and mitigate safety concerns. Based on its clinical activity in R/R pediatric and adult B-ALL, as well as other B-cell malignancies within the phase I ALLCAR19 study (NCT02935257), it is now being investigated in adult patients with R/R B-ALL (FELIX study; NCT04404660).¹

Below, we summarize key efficacy and safety data from the FELIX study, presented by Roddie at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

Study design

This is an open-label, multi-center, single-arm phase Ib/II study, which included adult patients aged ≥18 years with R/R B-ALL and ≥5% bone marrow (BM) blasts. The treatment schedule involved a split dose infusion of obe-cel on Day 1 and Day 10 up to a target dose of 410 x 10⁶ CAR T cells. To maximize therapeutic benefit, the dosing schedule was adjusted based on tumor burden prior to lymphodepletion and severity of toxicities after first infusion (Figure 1).

The primary endpoint was overall remission rate, defined as a complete response (CR) or CR with incomplete blood count recovery (CRi) by central assessment. Secondary endpoints included duration of response, event-free survival, overall survival, minimal residual disease (MRD) negativity rate, and safety.

Figure 1. Study design* 

BM, bone marrow; CAR, chimeric antigen receptor; CRS, cytokine release syndrome; Cy, cyclophosphamide; DLT, dose-limiting toxicity; Flu, fludarabine; ICANS, immune effector cell-associated neurotoxicity; obe-cel, obecabtagene autoleucel.
*Adapted from Roddie, et al.¹

Results

Of the 112 patients enrolled, 84% were infused with obe-cel, 94% of whom received both infusions. Patients were heavily pretreated and presented with high disease burden; baseline characteristics are summarized in Table 1.

Table 1. Baseline characteristics*

Efficacy and cellular kinetics

At the median follow-up of 9.5 months, 76% of patients achieved a CR/CRi. MRD negativity at a sensitivity level of 10^-4 by flow cytometry was achieved by 97% of responders, and durable responses were observed in 61% of responders. The median duration of response was 14.1 months.

Consistent with the ALLCAR19 study, obe-cel demonstrated early expansion with ongoing CAR T persistence.

Safety

Among all patients infused, the incidence of any-grade cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) was 75.5% and 25.5%, respectively; with Grade ≥3 CRS or ICANS observed in 3.2% and 7.4% of patients, respectively. The rate of CRS and ICANS was relative to disease burden, higher in patients with high (>20% BM blasts) versus low (≤20% BM blasts) tumor burden at lymphodepletion. For CRS, tocilizumab was given to 56% of patients, steroids in 17%, and vasopressor was only required in 3%.

Overall, any grade and Grade ≥3 treatment-emergent adverse events occurred in 98.9% and 78.7% patients, respectively. The most common Grade ≥3 treatment-emergent adverse events were neutropenia, thrombocytopenia, febrile neutropenia, and anemia (Figure 2). Only one treatment-related death was reported.

Figure 2. Most common Grade ≥3 TEAEs* 

TEAE, treatment-emergent adverse event.
*Data from Roddie, et al.¹

Presenter’s conclusion

In the phase II FELIX study, obe-cel demonstrated deep and durable responses, and a manageable safety profile in heavily pretreated adult patients with R/R B-ALL. High CR/CRi rates, high numbers of MRD-negative remissions, ongoing persistence, and very low rates of Grade ≥3 CRS and ICANS were reported, thus obe-cel represents a promising option for this patient subset.