FDA Approval Sought for Obe-Cel in Relapsed/Refractory B-ALL

A biologics license application (BLA) seeking the approval of obecabtagene autoleucel (obe-cel) for the treatment of adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) has been submitted to the FDA.¹

The BLA is supported by updated findings from the phase 2 FELIX trial (NCT04404660), which were presented at the 2023 ASCO Annual Meeting.¹ Findings showed that at median follow-up of 9.5 months (range, 1.9-19.0) patients who received an obe-cel infusion (n = 94) achieved an overall response rate (ORR) of 76% (95% CI, 66%-84%; P < .0001) with a complete response (CR) rate of 54.3% and a CR with incomplete count recovery (CRi) of 21.3%. Additionally, 97% of patients who responded were minimal residual disease (MRD) negative at the 10^-4 level via flow cytometry.

At the data cutoff of March 16, 2023, 61% of responders were in ongoing remission with no new anti-cancer therapies; the median duration of response (DOR) was 14.1 months (95% CI, 5.9-not estimable).²

“We are looking forward to continuing working with the FDA through the regulatory approval process,” Christian Itin, PhD, chief executive officer of Autolus Therapeutics, said in a press release.¹ “I would like to thank the treating physicians, patients, caregivers, and the dedicated team at Autolus for their support, trust and commitment for the program to reach this important milestone.”

The investigational CAR T-cell therapy has a fast target binding off-rate designed to reduce excessive activation of the programmed T cells, resulting in less toxicity and T-cell exhaustion, enhanced persistence, and high levels of durable remissions in adult patients with relapsed/refractory B-ALL.¹

The open-label, multi-center study enrolled adult patients with relapsed/refractory B-ALL who have an ECOG performance status of 0 or 1. Patients who were positive for a Philadelphia chromosome were also eligible for enrollment if they were intolerant to a TKI, had failed 2 previous lines of treatment with any TKI or 1 line of a second-generation TKI, or had a contraindication to a TKI. Exclusion criteria for the study included a diagnosis of Burkitt's leukemia or lymphoma or chronic myeloid leukemia in lymphoid blast crisis; a history or presence of clinically relevant central nervous (CNS) system pathology; presence of CNS-3 or CNS-2 disease with neurological changes; prior CD19-targeted therapy other than blinatumomab (Blincyto); or grade 3 or higher neurotoxicity following blinatumomab.³

Eligible patients were enrolled onto the phase 2 trial and received bridging therapy during the obe-cel manufacturing period as well as preconditioning therapy with 30 mg/m² of fludarabine and 500 mg/m² of cyclophosphamide. This was then followed by split-dose infusion of obe-cel on day 1 and day 10 of treatment.³

The primary end point of the study was CR/CRi and secondary end points included event-free survival, overall survival, MRD-negativity rate, safety, and DOR.²

At baseline, the median age of patients who received an obe-cel infusion was 50 years (range, 20-81) and the median number of prior lines of therapy was 2 (range, 1-6). Most patients were refractory to their most recent prior line of therapy (53.2%) and did not receive prior stem cell transplant (61.7%). Patients received prior blinatumomab (35.1%), inotuzumab ozogamicin (Besponsa; 31.9%), and blinatumomab with inotuzumab (16%).²

In terms of safety, any-grade and grade 3 or higher cytokine release syndrome (CRS) occurred at rates of 75.5% and 3.2%, respectively. Any-grade and grade 3 or higher immune effector cell–associated neurotoxicity syndrome (ICANS) occurred at rates of 25.5% and 7.4%, respectively.²

Treatment-emergent adverse effects (TEAEs) of any grade were reported in 98.9% of patients. The most common any-grade TEAEs included CRS (75.5%), neutropenia/decreased neutrophil count (39.4%), thrombocytopenia/decreased platelet count (28.7%), nausea (28.7%), and pyrexia (27.7%). Grade 3 or greater TEAEs occurred at a rate of 78.7% and included neutropenia/decreased neutrophil count (36.2%), thrombocytopenia/decreased platelet count (25.5%), febrile neutropenia (25.5%), anemia (19.1%), ICANS (7.4%), hypotension (4.3%), CRS (3.2%), nausea (1.1%), and pyrexia (1.1%). One patient experienced an obe-cel-related death per investigator assessment, attributed to neutropenic sepsis and hemophagocytic lymphohistiocytosis.²

Updated findings from FELIX are slated to be presented at the upcoming ASH Annual Meeting in December 2023. Notably, the marketing authorization application for obe-cel for the treatment of patients with relapsed/refractory AML will be submitted to the European Medicines Agency in the first half of 2024, according to Autolous.¹

References

1. Autolus Therapeutics submits biologics license application to US Food and Drug Administration for obecabtagene autoleucel (obe-cel) for patients with relapsed/refractory (r/r) adult B-cell acute lymphoblastic leukemia (ALL). News release. Autolus Therapeutics. November 27, 2023. Accessed November 27, 2023. https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-submits-biologics-license-application-us
2. Roddie C, Sandhu KS, Tholouli E, et al. Safety and efficacy of obecabtagene autoleucel (obe-cel, AUTO1), a fast-off rate CD19 CAR, in relapsed/refractory adult B-cell acute lymphoblastic leukemia (r/r B-ALL): top line results of the pivotal FELIX study. J Clin Oncol. 2023;41(suppl 16):7000. doi:10.1200/JCO.2023.41.16_suppl.7000
3. 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 August 28, 2023. Accessed November 27, 2023. https://clinicaltrials.gov/study/NCT04404660