On August 27, 2024 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported a poster presentation at the Society of Hematologic Oncology (SOHO) Annual Meeting being held September 4-7, 2024 in Houston, Texas (Press release, Autolus, AUG 27, 2024, View Source [SID1234646125]). These data demonstrate the rationale for tumor burden (TB)-guided dosing in adult patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (r/r B-ALL) by analyzing the impact of bone marrow (BM) blast percentage prior to lymphodepletion in patients treated with obe-cel in the FELIX Phase 1b/2 study.
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"Unlike other CD19 CAR T-cell therapies, obe-cel is administered to patients as two infusions using a tumor burden-guided dosing schedule," said Dr. Christian Itin, Chief Executive Officer of Autolus. "The data demonstrate the importance of administering both split doses of obe-cel to patients with r/r B-ALL and highlight the differentiation of obe-cel based on its unique binding properties and tumor burden-guided dosing approach."
Poster presentation:
Title: Obecabtagene autoleucel (obe-cel) for Relapsed/Refractory Adult B-Cell Acute Lymphoblastic Leukemia (r/r B-ALL): Impact of Chimeric Antigen Receptor T-Cell (CAR T) and Tumor Burden-Guided Dosing in the FELIX Phase 1b/2 Study
Session date and time: Wednesday, September 4, 6:15 pm
Session room: Hall B3
Poster Number: ALL-502
Presenting Author: Dr. Elias Jabbour, Professor, Department of Leukemia, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX
Summary:
Tumor burden (TB) is a recognized driver of immunotoxicity from CAR T therapy for B-ALL. Obe-cel is a novel autologous CAR T with a differentiated fast off-rate CD19 binding domain and a 4-1BB co-stimulatory domain, designed to improve CAR T persistence and immunotoxicity. Obe-cel is an investigational therapy being evaluated in adult r/r B-ALL in the FELIX Phase Ib/II study (NCT04404660), utilizing TB-guided dosing based on bone marrow (BM) blast percentage prior to lymphodepletion. We report outcomes by TB, demonstrating the rationale for TB-guided dosing in adult r/r B-ALL.
Of 127 patients infused with obe-cel, 120 (94%) received the planned two doses (low TB: n=48 [40%]; high TB: n=72 [60%]). Overall, high CAR T expansion was observed, which progressively increased with TB; a TB increase of 50% was associated with a 1.754-fold increase in Cmax and a 2.068-fold increase in AUC0–28days. In both groups, peak expansion was reached after Dose 2 (low/high TB: Day 15 [6–55]/Day 11 [2–28]), demonstrating the need for both doses regardless of TB. Overall remission rate was 90% and 75% in low and high TB groups, respectively.
In summary, TB-guided dosing was associated with high CAR-T cell expansion and while providing a manageable adverse event profile. This supports the TB guided-dosing approach in adult r/r B-ALL.