Claire Roddie, MD, PhD, presents data from the pooled analysis of the ongoing FELIX phase Ib/II study investigating obecabtagene autoleucel in R/R B-cell ALL.

Obecabtagene Autoleucel (obe-cel, AUTO1) for Relapsed/Refractory Adult B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL): Pooled Analysis of the Ongoing FELIX Phase Ib/II Study

Obe-cel is an autologous chimeric antigen receptor (CAR) T cell product with a novel CD19 binding domain CAT conferring a fast antigen off-rate designed to mitigate safety concerns and improve persistence over approved CD19 CAR T therapies.

Early results from the pivotal FELIX study Phase IIA cohort (N=94) were recently presented (Roddie C et al. J Clin Oncol 2023;41[16 Suppl]:7000). We report findings from a pooled analysis of all patients (pts) treated to date with obe-cel in the FELIX Phase Ib/II study (NCT04404660), with a focus on pts with low leukemia burden prior to obe-cel infusion.

The FELIX study enrolled adults with R/R B-ALL at screening with either morphological disease ≥5% bone marrow (BM) blasts (Cohort A), or in ≥2nd complete remission (CR)/CR with incomplete hematologic recovery (CRi) with measurable residual disease (MRD) (Cohort B), or with isolated extramedullary disease (EMD) (Cohort C).

The Phase Ib part of the study enrolled Cohorts A and B; the Phase II part enrolled Cohorts A, B, and C. CAR T products were generated from leukapheresis material using an automated process.

Pts received bridging therapy as needed and lymphodepletion with fludarabine (4 × 30mg/m2) and cyclophosphamide (2 × 500mg/m2). A target dose of 410 × 106 CAR T cells was infused as a split dose on Days 1 and 10 based on pre-lymphodepletion BM blast burden.

The primary endpoint was overall remission rate (best response of CR/CRi by independent review). Secondary endpoints included duration of remission (DoR), MRD negative remission rate, safety, and CAR T expansion/persistence.

This pooled analysis included data from pts treated with obe-cel across all cohorts in the Phase Ib/II parts of the study.

Low leukemia burden was defined as morphological remission per investigator assessment (<5% BM blasts without EMD) as measured at screening or at the start of lymphodepletion.

Between September 2020 and December 2022, 152 pts were enrolled and underwent leukapheresis. As of 16 March 2023, obe-cel was successfully administered to 126/152 (83%) pts (Phase Ib: Cohort A n=13, B n=3; Phase II: Cohort A n=94, B n=9, C n=7). Baseline characteristics at screening (n=126): median age 46.5 (range 20–81) yrs; Philadelphia positive B-ALL 27%; median 2 (range 1–6) prior lines of therapy; prior blinatumomab/inotuzumab 42%/32%; median BM blast burden 37% (range 0–100) including 23% pts with EMD; prior allogeneic stem cell transplant 44%.

At a median follow up of 11.0 (range 0.9–30.6) months, the CR/CRi rate was 77% (95/124 response evaluable pts) with CR rate 57% (71/124). Among MRD evaluable responders, 96% achieved MRD negative status by central flow cytometry analysis. Median DoR was not reached at the current follow up.

Low rates of Grade (Gr) ≥3 cytokine release syndrome (CRS; 2.4%) and/or Gr ≥3 immune effector cell associated neurotoxicity syndrome (ICANS; 7.1%) were observed.

CAR T expansion was similar across the Phase Ib/II cohorts and CAR T persistence was ongoing in the majority of responders at the current follow up.

Preliminary data indicate favorable efficacy and safety in pts with low leukemia burden prior to obe-cel infusion. Among 12 pts with MRD at screening (Cohort B), two pts were not evaluable and 9/10 evaluable pts achieved CR/CRi, with 100% achieving MRD negative status by central flow cytometry analysis post obe-cel. Median DoR was not reached at the current follow up. In this subset, no Gr ≥3 CRS was observed; one pt had Gr ≥3 ICANS.

In a subset of 28 pts (across all cohorts) in morphological remission at the time of lymphodepletion, 24/27 (89%) response evaluable pts achieved CR/CRi and 100% of MRD evaluable responders achieved MRD negative CR/CRi by central flow cytometry analysis post obe-cel. Median DoR was not reached at the current follow up. In this subset, no pts experienced Gr ≥3 CRS/ICANS.

This pooled analysis of data from all pts treated to date in the FELIX study demonstrates high rates of CR/CRi after obe-cel treatment, durable responses (median DoR not reached), and a favorable safety profile.

Preliminary data suggest better outcomes in pts with low leukemia burden at screening/lymphodepletion, with higher rates of deep MRD negative complete remission, median DoR not reached at the current follow up, no Gr ≥3 CRS and one Gr ≥3 ICANS.

These data support further exploration of CAR T therapy earlier in the treatment algorithm for adults with ALL.

Roddie C, Sandhu K, Shaughnessy P et al. Obecabtagene Autoleucel (obe-cel, AUTO1) for Relapsed/Refractory Adult B-cell Acute Lymphoblastic Leukemia (R/R B-ALL): Pooled Analysis of the Ongoing FELIX Phase Ib/II Study. Presented at: 65th ASH Annual Meeting and Exposition, December 9-12, 2023. San Diego, California.

Videos

Claire Roddie, MD, PhD, presents data from the pooled analysis of the ongoing FELIX phase Ib/II study investigating obecabtagene autoleucel in patients with relapsed/refractory adult B-cell acute lymphoblastic leukemia.

Claire Roddie, MD, consultant hematologist, University College London Hospital, discusses the patient population and topline efficacy findings from the phase 1/2 FELIX trial (NCT04404660), which is investigating the CD19-directed CAR T-cell therapy obecabtagene autoleucel in patients with relapsed/refractory adult B-cell acute lymphoblastic leukemia.

Patients with relapsed B-ALL are difficult to treat, and the FELIX trial population included patients with high disease burden, Roddie says. Patients in this trial had a median age of 50 years, and 26.6% had Philadelphia chromosome (Ph)–positive disease. Moreover, patients had a median of 2 prior lines of therapy, and 30.9% of patients had received at least 3 prior lines. A total of 53.2% of patients were refractory to their last line of prior therapy. At screening, the median percentage of bone marrow blasts in the patients who received obe-cel was 49.5%. In addition, at pre-conditioning, 19.1% of patients had extramedullary disease, which confers a poor prognosis in patients with ALL, Roddie notes.

A total of 94% of patients who underwent leukapheresis received obe-cel in the trial, which is an encouraging number given the challenging patient population, Roddie explains. The median time from vein to release of obe-cel was 21 days. This quick turnaround time is important in this population, as patients with rapidly progressing disease cannot tolerate long periods without therapy, Roddie emphasizes.

In FELIX, the overall response rate (ORR) was 76%, and the complete response rate was 54.3%. Furthermore, 97% of evaluable responders achieved minimal residual disease negativity. At a median follow-up of 9.5 months, 61% of responders were in ongoing remission and had not received new anticancer therapies.

A subgroup analysis demonstrated ORRs of 95% in patients at least 65 years of age and 88% in patients with Ph-positive disease. Additionally, patients who had received 4 or more prior lines of therapy achieved an ORR of 58%, patients who had extramedullary disease at pre-conditioning had an ORR of 56%, and patients with over 75% to 100% bone marrow blasts achieved an ORR of 58%.

Dr Roddie reports honoraria from Autolus Therapeutics; consulting or advisory roles with Autolus Therapeutics; research funding from Autolus Therapeutics (Inst); and travel, accommodations, and expenses from Autolus Therapeutics.

Claire Roddie, MD, discusses the patient population and topline efficacy findings from the phase 1/2 FELIX trial, which is investigating the CD19-directed CAR T-cell therapy obecabtagene autoleucel in patients with relapsed/refractory adult B-cell acute lymphoblastic leukemia.

Dr Roddie on Obe-cel in R/R B-ALL

Claire Roddie, MD, hematologist, the University College London Hospital, London, UK, discusses the potential utilization of obecabtagene autoleucel (obe-cel; previously referred to as AUTO1) in relapsed/refractory acute lymphoblastic leukemia (ALL).

When utilizing CAR T-cell therapies, T-cells could signal to the point of not being functional in the patient, Roddie explains. However, obe-cel, a second-generation CD19 CAR T-cell agent, features a different binding kinetic than previous agents used in this space, Roddie explains. Because obe-cel quickly releases from CD19, CAR T-cells secrete less cytokine, which helps reduced the risk of immune toxicities typically seen from these agents, Roddie adds.

Furthermore, the quick release from the CD19 antigen allows obe-cel to have lower exposure to the leukemia target cells, Roddie continues. This allows the CAR T cells to last for longer periods of time within patients, Roddie explains. Overall, those are the potential biological benefits in the design of obe-cel, Roddie concludes.

Claire Roddie, MD, discusses the potential utilization of obecabtagene autoleucel in relapsed/refractory acute lymphoblastic leukemia.


Claire Roddie, MD, PhD

Articles

Obecabtagene Autoleucel (obe-cel, AUTO1) for Relapsed/Refractory Adult B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL): Pooled Analysis of the Ongoing FELIX Phase Ib/II Study

Dr Roddie on Obe-cel in R/R B-ALL

Dr. Roddie on the Potential Utilization of Obe-Cel in R/R ALL