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3464 Alberta Cellular and Immunotherapy (ACIT) 001, Updated Results of Decentralized Production of Second Generation, Anti-CD19/41BB/CD3z Chimeric Antigen Receptor (CAR) T-Cells in Relapsed/Refractory (R/R) Acute Lymphoblastic Leukemia (ALL) and Aggressive Non-Hodgkin Lymphoma (NHL)

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, Lymphoid Leukemias, ALL, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, B Cell lymphoma, Diseases, Aggressive lymphoma, Lymphoid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Michael P. Chu, MD1, Zack Breckenridge, BSc2*, Deanna Hockley, PhD3*, Mona Shafey, MD4, Sunil J. Desai, MBBS, FRCPC5, Victor A. Lewis, MD6*, Peng Wang, MD, PhD7*, Vladimir Sapon-Cousineau, MD8*, Charles Yin, MD, PhD9, Carina Debes-Marun3* and Irwindeep Sandhu, MD10

1Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada
2University of Calgary, Calgary, Canada
3University of Alberta, Edmonton, Canada
4Tom Baker Cancer Centre and University of Calgary, Calgary, Canada
5Stollery Childrens Hospital, Edmonton, AB, CAN
6University of Calgary, Calgary, AB, Canada
7Department of Medicine, University of Alberta, Edmonton, AB, Canada
8Cross Cancer Institute, University of Alberta, Edmonton, Canada
9University of Alberta, Edmonton, AB, Canada
10Cross Cancer Institute, Edmonton, AB, Canada

Purpose

Anti-CD19 CAR T-cells are a standard treatment for aggressive B-cell cancers. Decentralized production may improve access to this important treatment and provide a platform for additional translational science in a single payer, public health care system such as Canada where implementation of CAR T-cells has been non-uniform. ACIT001/EXC002 is a phase 1b/2 clinical trial examining the feasibility, safety, and efficacy of decentralized production of anti-CD19 CAR T-cell using the CliniMACS Prodigy bioreactor to treat R/R ALL and NHL patients. We report the updated phase 1b and phase 2 lymphoma results in adults.

Methods

We previously reported the preliminary results of the phase 1b study, a 3+3 dose escalation design. CD19 expression was confirmed on their fresh or archival tumor samples and all patients had received a minimum of 2 prior lines of therapy. Patients with transformed disease or central nervous system (CNS) involvement were allowed to participate. Anti-CD19 CAR T-cells were manufactured using freshly apheresed peripheral blood T-cells using a Lentigen anti-CD19 vector. Patients received cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) as outpatient intravenous lymphodepleting chemotherapy on Days -5, -4 and -3 prior to infusion of CAR T-cells. Infusion of fresh CAR T-cells was favored but cryopreservation was permitted if clinical circumstances dictated a delay between apheresis and treatment. Patients were suggested to remain in hospital for 7 days at minimum but length of stay was not mandated. Safety and efficacy was met to proceed to phase 2 in NHL and ALL patients. Herein we report the aggregated, updated results on the phase 2 and phase 1b patients.

Results

In total, 30 patients have been accrued to date of which there were 7 ALL patients and 23 NHL (including 5 transformed); 5 had CNS involvement. In-specification products were manufactured for all but one patient (failed manufacturing, excluded from study); 28 patients received fresh CAR T-cells (1 cryopreserved due to contracting respiratory infection shortly after apheresis) at a median 14 days after apheresis (“vein-to-vein”, range 14-28 days) for <$100,000 CAD per product. Grade 1 or 2 cytokine release syndrome (CRS) occurred in 16 (55%) of patients with no grade 3 or higher incidents; tocilizumab was used in 14 (48%) of patients. Grade 1 or 2 Neurotoxicity (ICANS) occurred in 4 (14%) patients, and responded to limited dexamethasone. Median length of stay in hospital was 11 days (range 9-17 days). Investigator-assessed, objective response rate was 79% (n=23) including complete response (CR) in all ALL patients and 58% of NHL patients. With a median 16 months of follow-up time, 18 patients remain in remission.

Summary

Our combined phase 1b/2 results provide evidence that decentralized production is feasible in a single payer, public health care system. With a consistent vein-to-vein time of 14 days, we remove the inconsistency of manufacturing windows from standard of care products and have direct control over supply of CAR T-

cells for our patient population. This method also implies that having smaller local manufacturing facilities allows a savings of scale while promoting improved and faster service than the creation and maintenance of a large, centralized manufacturing facility. This particular CAR T-cell product demonstrates a safety profile and efficacy similar to standard-of-care products through. These results have prompted expansion to earlier line of therapy and additional B-cell subtypes.

Disclosures: Chu: Pfizer: Honoraria; BMS: Honoraria; Amgen: Consultancy; Janssen: Honoraria; AstraZeneca: Honoraria; Amgen: Honoraria; Kite/Gilead: Honoraria; Sanofi: Honoraria. Shafey: Roche: Honoraria; Janssen: Honoraria; BeiGene: Honoraria; AstraZeneca: Honoraria. Sandhu: Janssen, Celgene/BMS, Pfizer, Sanofi, GSK, Forus, Beigene: Honoraria; Janssen, Celgene/BMS, Pfizer, Sanofi, GSK, Forus, Beigene: Consultancy.

*signifies non-member of ASH