Claire Roddie PhD, FRCPath, MBChB, MRCP, on the Potential Advantage Obe-cel's Fast Off-rate CD19 Binding Domain

“...We know that other products on the market for adult acute lymphoblastic leukemia 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. 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 Therapeutics’ obecabatagene autoleucel (obe-cel) is an investigational autologous CD19-directed CAR-T therapy that incorporates a novel fast off-rate CD19 binding domain intended to shorten the time that CAR T-cells bind to leukemia cells, which could simultaneously decrease the number of cytokines secreted and reduce the rate of T-cell exhaustion. Obe-cel is currently being evaluated in adults with r/r B-ALL in the pivotal phase 2 FELIX clinical trial (NCT04404660), data from which were presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois, by Claire Roddie, MD, PhD, FRCPath, MBChB, MRCP, an associate professor in haemato-oncology at University College London.

In an interview with CGTLive™’s sister publication OncLive™, Roddie spoke about the advantage that the fast off-rate CD19 binding domain could provide, emphasizing its potential for reducing toxicity and increasing CAR T-cell persistence, both of which were illustrated in the data from FELIX that she presented at the conference. Roddie also discussed unmet needs that remain in r/r B-ALL, particularly with regard to manufacturing times for CAR-T therapies, and highlighted another presentation she was excited to see at ASCO’s 2023 conference: a study of real-world outcomes for Kite’s brexucabtageneautoleucel (Tecartus).

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REFERENCE
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. Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #7000