FDA Approves Obe-Cel for Adults With R/R B-Cell Precursor Acute Lymphoblastic Leukemia
The CAR-T therapy was approved based on the pivotal phase 1b/2 FELIX clinical trial (NCT04404660), which showed good rates of overall complete remission and median duration of remission.
Elias Jabbour, MD
(Credit: MD Anderson)
The FDA announced that is has approved obecabtagene autoleucel (Aucatzyl; Autolus Inc), known colloquially as obe-cel, a CD19-directed genetically modified autologous T-cell immunotherapy, for the treatment of adults with relapsed or refractory (r/r) B-cell precursor acute lymphoblastic leukemia (ALL).1,2 The therapy was approved based on the findings of the pivotal phase 1b/2 FELIX clinical trial (NCT04404660), which showed rates of overall complete remission (CR) above 60% and a median duration of remission beyond 12 months for those who achieved complete remission within 3 months.2
The agency's total recommended dose of obe-cel is 410 × 106 CD19 chimeric antigen receptor (CAR)-positive viable T-cells, preceded by fludarabine and cyclophosphamide lymphodepleting chemotherapy and administered as split-dose infusion on Day 1 and Day 10 (±2 days) of treatment, based on bone marrow blast assessment. No REMS was required by the FDA.
“Adult ALL is an extremely aggressive cancer, and there is a high unmet medical need that exists in the treatment of patients with this disease once they relapse, where historically they suffer from poor outcomes,” Elias Jabbour, MD, the lead investigator of the US-based portion of the FELIX study and a professor of Leukemia and ALL section chief at The University of Texas MD Anderson Cancer Center, said in a statement.2 “This milestone approval, based on the demonstrated clinical benefit of Aucatzyl, brings new hope for adult patients with r/r B-ALL.”
The biologics license application for obe-cel was originally submitted in November 2023, supported by data from FELIX. All told, among 65 patients in the trial with evaluable efficacy data, 63% achieved overall CR, including 51% who achieved it at any time and 12% with CR with incomplete hematologic recovery. CR within 3 months—the main efficacy end point—was achieved by 42% of patients with a median duration of remission of 14.1 months.
Updated data from this clinical trial were presented as part of a pooled analysis with data from the phase 1 ALLCAR19 trial (NCT02935257) last year, at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California.3 ALLCAR19 was originally open to patients aged 16 years and older with r/r B-ALL, but later had its eligibility criteria expanded for an extension study that included patients with r/r B-cell chronic lymphocytic leukemia and r/r B-cell nonHodgkin lymphoma.
As for safety in FELIX, there were low levels of cytokine release syndrome (CRS) reported, with 3% of adverse events being deemed grade 3, and none labeled grade 4 or 5. Grade 3 or greater immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 7% of patients.
“Based on the experience in the FELIX trial Aucatzyl is highly active and can be well managed, offering an attractive risk benefit profile for B-ALL patients,” Claire Roddie, MD, PhD, FRCPath, the lead investigator of the FELIX study and Associate Professor of Haematology at the University College London (UCL) Cancer Institute, said in statement.2 “In the FELIX trial Aucatzyl has shown long term persistence and deep responses which we believe are critical for long term remissions in B-ALL.”
Obe-cel incorporates a novel fast off-rate CD19 binding domain intended to shorten the time that it takes for CAR T-cells bind to leukemia cells, which may simultaneously decrease the number of cytokines secreted and reduce the rate of T-cell exhaustion.4 Last year, at the American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2-6, in Chicago, Illinois, CGTLive®'s sister site OncLive® spoke with Roddie about the potential advantage of this design, where she noted that, “...We know that other products on the market for adult ALL have got significant toxicity profiles and that's actually really difficult for us physicians to manage and particularly difficult for the patients and their families.”
“It makes it difficult to anticipate or imagine a clinical world where we can give these comfortably as outpatient therapies, which is obviously where [we want to go]—we want to be able to improve the patient experience, quality of life, etc.," Roddie told OncLive. "And so, I think that's where obe-cel comes into this because the toxicity profile is so much less difficult for patients to tolerate—even patients with lots and lots of disease—and I think that's its biggest selling point. From the perspective of just safely navigating patients through this therapy, it’s much more straightforward.”
Autolus noted that the CAR-T treatment will be manufactured at the company's dedicated site, called 'the Nucleus,' located in Stevenage, United Kingdom. It was granted a Manufacturer’s Importation Authorization and a GMP certificate from the UK's Medicines and Healthcare products Regulatory Agency in March 2024, and was inspected as part of the FDA's process. Cardinal Health will serve as Autolus’ commercial distribution partner in the United States.
