Phase 2 FELIX study results show 21.3% of the 94 patients infused with obecatagene autoleucel achieved a complete response or complete response with incomplete count recovery.
In adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) treated with the CD-19-drected CAR T-cell therapy, obecatagene autoleucel (Obe-cel; AUTO1), had a 76% complete response rate (CR) or complete response with incomplete count recovery (CRi) rate, according to top-line results of the pivotal phase 2 FELIX trial (NCT04404660) that were presented during the 2023 ASCO Annual Meeting.1
Specifically, 54.3% of patients who were infused (n = 94), had a CR and 21.3% had a CRi. The objective response rate was 76% (95% CI, 66%-84%; P <.0001). Additionally, 97% of patients who responded and had evaluable samples were minimal residual disease (MRD)–negative at the 10-4 level via flow cytometry.
“We are dealing with a very difficult patient population here. They are heavily pretreated, they’re older, they’re comorbid, they have got a lot of extra disease on board; there was a lot of extramedullary disease,” lead study author Claire Roddie, MD, associate professor in haemato-oncology, in the research department of haematology, of University College London Cancer Institute, said in an oral presentation of the data. “But despite all of these odds being stacked against the product, obe-cel was able to achieve CR or CRi in 76% of those infused patients, and what’s more is those responses were deep, MRD-negative responses.”
Obe-cel is designed to mitigate safety concerns and improve persistence, she explained. Previously, obe-cel was evaluated in other settings, including relapsed/refractory pediatric B-ALL,2 adult B-ALL,3 and other hematologic cancers (NCT02935257).4
In FELIX, patients underwent leukapheresis after screening and received bridging therapy during obe-cel manufacturing. At day -6, pre-conditioning therapy was administered with fludarabine at 30 mg/m2 and cyclophosphamide at 500 mg/m2. Obe-cel was administered at a split-dose infusion on days 1 and 10. Patients were then followed for safety and efficacy.
The split-dosing schedule was tumor burden-adjusted to maximum the treatment’s therapeutic index, Roddie noted. For example, if patients had bone marrow (BM) blasts up to 20% during the pre-conditioning stage, treatment was given at 100 x 106 CAR T-cell dose and, if any events of cytokine release syndrome (CRS) were below grade 2 and there were no cases of immune effector cell-associated neurotoxicity syndrome (ICANS), obe-cel was administered again at a 310 x 106 CAR T-cell dose.
Similarly, for patients whose BM blasts were greater than 20%, then obe-cel was first given at 10 x 106 CAR T-cell dose. Following the same CRS/ICANS score, treatment was then given at 400 x 106 CAR T cells.
Roddie added that 94% of infused patients (n = 94) received both obe-cel infusions.
Regarding baseline characteristics, the median age was 50 years (range, 20-81), and 50% of patients were female. A total 26.6% of patients were Philadelphia chromosome positive. The median line of therapies received was 2 (range, 1-6); 30.9% of patients had at least 3 prior lines of therapy. Additionally, 53.2% of patients were refractory to their last prior line of therapy, and 38.3% had underwent allogeneic stem cell transplant. A total 35.1% received prior blinatumomab (Blincyto), 31.9% had prior inotuzumab ozogamicin (Besponsa), and 16.0% had received both agents.
The median percentage of BM blasts at screening and at time of pre-conditioning was 49.5% (range, 6%-100%) and 41.1% (range, 0%-100%), respectively. Eighteen patients (19.1%) had extramedullary disease at the time of pre-conditioning.
Manufacturing of obe-cel was also assessed and was found to be reliable and consistent with the product released for the 94% of patients who underwent leukapheresis. Ninety-six percent of products reached the target dose, the median transduction efficiency rate was 72%, and the median time from vein to release was 21 days.
Further findings showed that 61% of responders were in ongoing remission sans new treatment at a median follow-up of 9.5 months. The median duration of response was 14.1 months (95% CI, 5.9-not estimable).
Roddie also unveiled data from a subgroup analysis of responders as part of an independent response review committee assessment. High-risk subgroups, she noted, included those with extramedullary disease and high BM blasts at pre-conditioning.
Regarding safety, any-grade and grade 3/4 CRS was observed in 75.5% and 3.2% of infused patients, respectively; these rates were 64.9% and 2.7% in those with BM blasts that were up to 20% at preconditioning (n = 37) and 82.5% and 3.5%, respectively, in those whose BM blasts were greater than 20% (n = 57).
Any-grade and grade 3/4 ICANS rates were 25.5% and 7.4%, respectively, in all infused patients. When broken down by BM blasts, these rates were 13.5% and 2.7%, respectively, in those with BM blasts up to 20% and 33.3% and 10.5%, respectively, in those with BM blasts that were greater than 20%.
Roddie noted that 56% and 17% of patients received tocilizumab (Actemra) and steroids, respectively, to manage CRS, and 3% of patients required vasopressor for CRS. Eighty-six percent of grade 3 or higher ICANS events were observed in those with more than 75% of BM blasts at pre-conditioning.
Any-grade and grade 3 or higher treatment-emergent adverse effects (TEAEs) were reported in 98.9% and 78.7% of patients, respectively. The most common grade 3 or higher TEAEs were comprised of neutropenia (36.2%), thrombocytopenia (25.5%), febrile neutropenia (25.5%), and anemia (19.1%). One death, which was due to hemophagocytic lymphohistiocytosis and neutropenic sepsis, was related to obe-cel by investigator assessment.
“I think we also need to acknowledge the fact this is a safe product to give to those older, comorbid patients,” Roddie said.
Expansion and persistence data with obe-cel was found to be consistent with that found in the ALLCAR19 study3 (Cmax copies/ug in FELIX, 114,982 vs ALLCAR19, 127,152; Tmax days, 14 vs 13; AUC0-28d copies/ugxd, 1,139,380 vs 1,251,802).
Editor’s Note: Dr Roddie cited honoraria, consulting or advisory roles, and travel expenses with Autolus Therapeutics.
1. 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
2. Ghorashian S, Kramer AM, Onuoha S, et al. Nat Med. 2019;25(9):1408-1414. doi:10.1038/s41591-019-0549-5
3. Roddie C, Dias J, O’Reilly MA, et al. J Clin Oncol. 2021;39(30):3352-3363. doi:10.1200/JCO.21.00917
4. Roddie C, Pinto JDA, O’Reilly M, et al. Blood. 2022;140(suppl 1):7452-7453. doi:10.1182/blood-2022-167053