On September 1, 2021 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported publication of the obecabtagene autoleucel (obe-cel) Phase 1 ALLCAR19 data in Journal of Clinical Oncology1 (Press release, Autolus, SEP 1, 2021, View Source [SID1234587114]). Obe-cel is a fast off-rate CD19 CAR-T therapy, designed to reduce toxicity and improve engraftment1,2. ALLCAR19 is a clinical study in collaboration with Autolus’ academic partner, UCL [NCT02935257].
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"Currently there are no CD19 CAR T therapies approved for use in adult B-ALL and there exists a significant unmet need for r/r B-ALL patients," said Dr. Claire Roddie, Consultant Hematologist, UCL Cancer Institute and University College London Hospital. "We are very encouraged by the clinical profile of obe-cel, which demonstrates high sustained responses rates with remarkably little immunotoxicity despite high disease burden in many patients."
"We designed obe-cel, a unique rapid binding off rate CD19 CAR-T therapy, to specifically tackle the challenges of existing CD19 CAR T therapies, namely toxicity and lack of durable responses, by reducing the magnitude of T cell activation from each target cell interaction," said Dr. Martin Pulé, chief scientific officer of Autolus. "We have seen our design features play out in the clinical setting and these data further support our decision to progress obe-cel into the ongoing pivotal FELIX study [NCT04404660]."
Obe-cel demonstrated an excellent safety profile, with no patients experiencing high grade (≥ grade 3) cytokine release syndrome (CRS), despite the majority having a high disease burden prior to lymphodepletion1. In 8/20 patients developing grade 2 CRS, 7 patients received tocilizumab. No patients on study received corticosteroids for management of CRS1. Three of 20 patients experienced grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) and all resolved within 24-72 hours to grade 1 or less with corticosteroids1.
CAR T cell concentration reached very high levels at peak and persistence in peripheral blood was evident in 15/20 (75%) patients at a median of 166.5 days, with 4/20 (20%) patients having follow-up duration over 2 years, and 3/4 of these with ongoing CAR persistence at data cut off1. Interestingly, B-cell aplasia was ongoing in 15/20 patients at last observation1.
Of the 20 patients treated in the ALLCAR19 study, 85% patients achieved minimal residual disease (MRD) negative complete response (CR) at month 11. Duration of response remains highly encouraging. With a data cut-off date of May 17, 2021 and as presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress in June 2021, event free survival (EFS) at 12 months and 24 months was 50.2%, with median EFS not reached across all patients treated3.
Overall, obe-cel’s profile of durability and favorable toxicity is consistently observed across the B cell malignancies tested so far, with data on a total of 50 patients reported to date, including patients with adult ALL1 in ALLCAR19 [NCT02935257], pediatric ALL2 [NCT02443831] and indolent B-cell lymphomas3 [NCT02935257]. Alongside the FELIX study, a potential pivotal study ongoing in adult ALL, we continue to explore the profile of obe-cel in patients with other B-cell lymphomas through additional cohorts in the ALLCAR19 study and in patients with primary CNS lymphomas (PCNSL) through the CAROUSEL study [NCT04443829].
Citations (and hyperlinks)
Roddie et al. "Durable responses and low toxicity after fast off-rate CD19 CAR-T therapy in adults with relapsed/ refractory B-ALL." DOI: 10.1200/JCO.21.00917 Journal of Clinical Oncology – published online before print August 31, 2021
Ghorasian et al. "Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR." Nature Medicine volume 25, pages1408–1414(2019) (Sept 25, 2019)
Roddie et al. "Early Safety and Efficacy Findings of AUTO1 (CAT19), a Fast-Off Rate CD19 CAR, in Relapsed/Refractory Indolent B Cell Lymphomas." EHA (Free EHA Whitepaper) annual meeting, June 11 2021, abstract EP788. EHA (Free EHA Whitepaper) Investor slide presentation