Claire Roddie PhD, FRCPath, MBChB, MRCP, on Evaluating Obe-cel in Patients With R/R B-ALL

“...As we all know, relapsed and refractory adult acute lymphoblastic leukemia is a very challenging clinical condition. As it stands, there haven't been any sort of curative therapies in this setting and so CD19 CAR T-cell therapy has really been pretty transformative in this space—in the leukemia setting, particularly in pediatrics. In adults, it's been more challenging, and part of the reason for that is CD19 CAR-Ts have been conventionally and traditionally associated with high levels of immune toxicity, which has meant it's been more difficult to give to frailer and older patients. So that's where obe-cel comes in...”

Although chimeric antigen receptor T-cell (CAR-T) therapies have transformed the treatment landscape for relapsed/refractory (r/r) hematological malignancies such as B-cell acute lymphoblastic leukemia (B-ALL), currently marketed CAR-T products continue to have substantial drawbacks. Among the challenges that researchers are attempting to overcome with the development of new CAR-T therapies are the potentially high levels of toxicity caused by CAR-T products and the limited persistence of CAR T-cells in patients’ bloodstreams.

Autolus Therapeutics’ obecabatagene autoleucel (obe-cel), an investigational autologous CD19-directed CAR-T therapy, utilizes a fast off-rate CD19 binding domain. The novel binding domain is intended to shorten the time that CAR T-cells bind to cancer cells, which could simultaneously decrease the amount of cytokines secreted and reduce the rate of T-cell exhaustion. Obe-cel is currently being evaluated for the treatment of 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 discussed obe-cel's fast off-rate CD19 binding domain and the potential advantages it could offer over binding domains used in currently marketed CD19-directed CAR-T therapies. She also gave an overview of the key efficacy and safety results she presented from FELIX at the conference, which included 76% of treated patients achieving a complete remission (CR) or a CR with incomplete blood count recovery.

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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