Obe-cel is an investigational CD19 CAR T-cell therapy currently in clinical trials for relapsed/refractory B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma.
Top-line data from the phase 2 FELIX trial showed positive results from treatment with obe-cel (Autolus Therapeutics plc) in adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). These data were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.
Study investigators enrolled 112 adult patients with r/r ALL into the morphological cohort of the FELIX trial, of whom 94 (84%) patients were administered obe-cel. Among the treatment cohort, 76% achieved a complete response (CR) or CR with an incomplete hematological recovery (CRi). Further, 97% of responders to treatment who had evaluable samples showed deep remission with no detectable minimal residual disease (MRD).
At a 9.5-month median follow up, the investigators found that 61% of responders remained in ongoing remission without the addition of new anti-cancer therapies. Further, chimeric antigen receptor (CAR) T-cell kinetics showed outstanding CAR T engraftment and persistence that was consistent with the previously conducted ALLCAR19 study, according to Autolus Therapeutics.
“We are very encouraged by the outcome of the FELIX study. Obe-cel shows low immunotoxicity, high complete remission rates and excellent CAR T expansion and persistence in adult B-ALL,” said Claire Roddie, MD, PhD, associate professor at University College London, honorary consultant hematologist at University College London Hospital, in a press release. “These data are consistent with the prior ALLCAR19 study and suggest that obe-cel has the potential for long-term clinical benefit in adult B-ALL patients without additional therapies.”
Obe-cel is an investigational CD19 CAR T-cell therapy developed with the intent of overcoming the limitations in the clinical activity and safety of current CD19 CAR T cell therapies, according to Autolus. Obe-cel, which was designed to have an accelerated target binding off-rate to lower excessive activation of the programmed T cells, may decrease toxicity and be less prone to T cell exhaustion, according to Autolus.
The investigators posited that this may enhance persistence and the ability of programmed T cells to hunt and kill target cancer cells. Obe-cel is also currently being analyzed in phase 1 clinical trials for B-cell non-Hodgkin lymphoma.
The safety profile of obe-cel showed “a potentially best-in-class” tolerability profile, according to Autolus Therapeutics. The researchers observed grade ≥3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 3% (3/94) and 7% (7/94) of patients, respectively. The researchers observed that the majority of the toxicity occurred among patients with a high disease burden.
They noted that 6 of 7 grade ≥3 ICANS were found in those with a very high tumor burden of more than 75% bone marrow blasts at lymphodepletion. Grade ≥3 adverse events were observed in 79% of the overall patient population, with the most common being neutropenia (36.2%), and thrombocytopenia (25.5%).
“We are pleased that our pivotal FELIX study confirms the attractive product profile for obe-cel, combining a high level of clinical activity with an excellent safety profile which we know is critical for this highly pre-treated and frail patient population,” said Christian Itin, PhD, chief executive officer of Autolus, in the release. “Conducting this study through the pandemic was a pressure test for obe-cel's product profile and our ability to deliver obe-cel reliably under difficult circumstances. We would like to thank patients, their caregivers, nurses and treating physicians for their participation in the FELIX study. With the Nucleus, our commercial manufacturing facility, well advanced in validation we look forward to submitting a BLA towards the end of this year and working with the FDA to get obe-cel to patients as soon as possible.”
Autolus Therapeutics Presents Positive Results from Pivotal Phase 2 FELIX study in adult r/r B-ALL at ASCO. Autolus Therapeutics. News release. June 2, 2023. https://finance.yahoo.com/news/autolus-therapeutics-presents-positive-results-110000898.html