Obecabtagene Autoleucel Meets Primary End Point of ORR in R/R B-cell Acute Lymphoblastic Leukemia

Obecabtagene autoleucel (obe-cel) elicited an overall remission rate (ORR) of 70% in 50 efficacy-evaluable adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), meeting the primary end point of the phase 2 FELIX trial (NCT04404660).¹

At a median follow-up of 6.4 months, the investigational CAR T-cell therapy demonstrated comparable expansion and initial persistence to that observed in the ALLCAR19 study (NCT02935257).

Moreover, a safety analysis of 92 evaluable patients treated with obe-cel revealed that 3% of patients experienced cytokine release syndrome that was grade 3 or higher. Twenty-three percent of patients reported any-grade immune effector cell–associated neurotoxicity (ICANS); this effect was grade 3 or higher in 8% of patients.

“Obe-cel’s high level of anti-leukemia activity combined with a well manageable tolerability profile is a significant step forward in this underserved disease setting, which is characterized by the explosive growth of the leukemia and the poor condition of many patients,” Jae Park, MD, associate attending physician at Memorial Sloan Kettering Cancer Center, stated in a press release. “The expansion and initial persistence of obe-cel are encouraging from a long-term outcome perspective and I look forward to the next data update and the potential of obe-cel as a treatment for ALL.”

The mechanism of action of obe-cel mimics physiological T-cell receptor interactions. Additionally, the therapy has a lower affinity for CD19 than similar CAR T-cell products. The design allows for avoidance of CAR T-cell over-activation and exhaustion. Notably, the half-life of the drug’s target interaction is 9.8 seconds.^2,3

The open-label, multicenter, single-arm FELIX study is enrolling adult patients with relapsed or refractory B-ALL. To be eligible for enrollment, patients were required to be at least 18 years of age, have an ECOG performance status of 0 or 1, and documented CD19 positivity within 1 month of screening.⁴

Specifically, for the phase 1b and 2 portions of the research, patients needed to have 5% or greater blasts in bone marrow at screening to be included in the primary cohort. Exploratory cohorts will include those with minimal residual disease (MRD) positivity, defined as at least detectable disease at 1 × 10-4 and less than 5% blasts in the bone marrow at screening. Those previously treated with a CD19-targeted therapy other than blinatumomab (Blincyto) and those who have experienced neurotoxicity of grade 3 or higher after treatment with blinatumomab will be excluded.

Participants will sequentially complete screening, leukapheresis, preconditioning with cyclophosphamide and fludarabine chemotherapy, and follow-up. Obe-cel is administered at a total target dose of 410 × 106 CAR T cells on day 1 and day 10 as a split dose, plus or minus 2 days.

The trial had a phase 1b component that was completed before proceeding to the single-arm phase 2 clinical trial. The primary end point of the research was ORR, which was defined as the proportion of patients achieving complete remission (CR) and CR with incomplete blood count recovery by independent response review committee assessment. Key secondary end points include duration of response, MRD-negative CR rate, and safety.

“We are really pleased with the consistency of data from the interim analysis of the FELIX study with our prior results from the ALLCAR19 study in adult patients with relapsed/refractory ALL,” Claire Roddie, MD, associate professor of hematology, of the Cancer Institute, University College London, added in the press release.

Patients have been screened for entry into the morphological cohort of the trial, and the prespecified goal of about 90 patients enrolled has been reached, according to Autolus Therapeutics plc.

The company shared plans to present data from FELIX at an upcoming medical conference in mid-2023, with longer follow-up planned to be shared at the end of next year.

References

1. Autolus Therapeutics announces pivotal phase 2 FELIX clinical trial has met primary endpoint at interim analysis. News release. Autolus Therapeutics plc. December 8, 2022. Accessed December 20, 2022. https://bit.ly/3CdGjhl
2. Developing next generation programmed T cell therapies. Autolus Therapeutics. January 2022. Accessed December 20, 2022. bit.ly/3t2ydSX
3. Developing a transformational treatment for adult acute lymphoblastic leukemia. Autolus Therapeutics. Accessed December 20, 2022. bit.ly/3BFErfL
4. A study of CD19 targeted CAR T cell therapy in adult patients with relapsed or refractory B cell acute lymphoblastic leukaemia (ALL). ClinicalTrials.gov. Updated January 5, 2022. Accessed December 20, 2022. https://clinicaltrials.gov/ct2/show/NCT04404660