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650 Preliminary Safety and Efficacy of PBCAR0191, an Allogeneic ‘Off-the-Shelf’ CD19-Directed CAR-T for Patients with Relapsed/Refractory (R/R) CD19+ B-ALL

Program: Oral and Poster Abstracts
Type: Oral
Session: 704. Cellular Immunotherapies: Allogeneic CARs and CARs for T Cell Lymphomas
Hematology Disease Topics & Pathways:
Biological, Clinical Trials, Lymphoid Leukemias, ALL, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Clinical Research, Diseases, Therapies, Lymphoid Malignancies
Monday, December 13, 2021: 10:45 AM

Nitin Jain, MD1, Hagop Kantarjian, MD1, Scott R. Solomon, MD2, Fiona He, MD3, Craig S. Sauter, MD4, Christopher R. Heery, MD5, Alan F. List, MD5, Mark C. Johnson, PhD5*, Yu Lou, MSc5*, Monika Vainorius, MD5*, Koen Van Besien, MD, PhD6, Adam J. Olszewski, MD7, Anthony S. Stein, MD8 and Bijal D. Shah, MD9

1The University of Texas MD Anderson Cancer Center, Houston, TX
2Northside Hospital Cancer Institute, Atlanta, GA
3University of Minnesota, Minneapolis, MN
4Memorial Sloan Kettering Cancer Center, New York, NY
5Precision BioSciences, Inc., Durham, NC
6Presbyterian/Weill Cornell Medical College, New York, NY
7Rhode Island Hospital, Providence, RI
8City of Hope National Medical Center, Duarte, CA
9H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

Introduction: CD19-directed autologous CAR-T products induce high response rates in adults with R/R B-ALL, yet many patients relapse within the first year. Additionally, cell manufacturing timelines, and poor t-cell fitness may imperil efficacy, especially among those with proliferative disease. This makes access to a donor-derived, readily available CAR-T product of great interest in this patient population, particularly when consolidation with allogeneic stem cell transplant (allo-SCT) is possible. We report preliminary safety, efficacy, and correlative data for the R/R B-ALL patients dosed with at least 3 x 106 CAR-T cells/kg of PBCAR0191, an allogeneic ‘off-the-shelf’ CD19-directed CAR-T.

Methods: Subjects were 18 years or older with CD19+ R/R B-ALL after at least 2 prior lines of therapy. Patients were required to have adequate organ function and no active GvHD, CNS disease, active infections, or other active medical issues. Prior allo-SCT and/or autologous CAR-T therapy were allowed. Subjects received either standard (sLD; 30mg/m2/day and 500mg/m2/day x 3 days fludarabine and cyclophosphamide, respectively) or enhanced (eLD; 30mg/m2/day x 4 days flu and 1000mg/m2/day x 3 days cy) lymphodepletion preceding PBCAR0191 infusion. Correlative laboratory samples were taken for CAR-T expansion, persistence, molecular response to treatment and safety assessments.

Results: As of August 2, 2021, 15 subjects with R/R CD19+ B-ALL have been dosed with dose Dose level 3/4a (3 X 106 CAR-T cells/kg or equivalent, n=11) or a Dose level 4b (flat dose of 5 X 108 CAR-T cells, n=4). Demographics, baseline disease, and prior treatment data are presented in the table. Most of the Adverse events (AE) reported to date were mild, with no cases of GvHD, no Grade ≥3 CRS and 1 case of Grade 3 ICANS which resolved within 48 hours. 67% of subjects treated (10/15) experienced PBCAR0191 related AEs, with 60% (9/15) of subjects experiencing serious AEs (one related to PBCAR0191, ICANS Grade 3).

The complete response (CR) or CRi (incomplete marrow recovery) rate at Day ≥28 is 33% (2/6) in DL3/4a and sLD, 80% (4/5) in DL3/4a with eLD and 75% (3/4) in DL4b with sLD. Importantly, 4/15 (27%) responding subjects underwent allo-SCT, with one additional subject not able to receive transplant due to eligibility yet maintaining an MRD- CR for >250 days, and one refusing to proceed with transplant. Product accessibility was evident compared to autologous CAR-T products, with median time from screening completion to PBCAR0191 infusion of 7 days (median of 1 day until start of LD) and all eligible subjects receiving PBCAR0191 infusion.

Conclusion: PBCAR0191 has demonstrated a manageable safety profile and high complete response rate at day 28 or later, providing an adequate window for potential bridge to allo-SCT.

Disclosures: Jain: Adaptive Biotechnologies: Honoraria, Research Funding; Precision Biosciences: Honoraria, Research Funding; Cellectis: Honoraria, Research Funding; Pfizer: Research Funding; Janssen: Honoraria; Genentech: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Beigene: Honoraria; TG Therapeutics: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding; Aprea Therapeutics: Research Funding; Incyte: Research Funding; AbbVie: Honoraria, Research Funding; Fate Therapeutics: Research Funding; Servier: Honoraria, Research Funding; ADC Therapeutics: Honoraria, Research Funding; Pharmacyclics: Research Funding. Kantarjian: KAHR Medical Ltd: Honoraria; Ascentage: Research Funding; Immunogen: Research Funding; Jazz: Research Funding; Aptitude Health: Honoraria; Ipsen Pharmaceuticals: Honoraria; Precision Biosciences: Honoraria; Novartis: Honoraria, Research Funding; Astra Zeneca: Honoraria; AbbVie: Honoraria, Research Funding; NOVA Research: Honoraria; BMS: Research Funding; Daiichi-Sankyo: Research Funding; Pfizer: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Astellas Health: Honoraria; Taiho Pharmaceutical Canada: Honoraria. Sauter: Bristol-Myers Squibb: Research Funding; GSK: Consultancy; Celgene: Consultancy, Research Funding; Gamida Cell: Consultancy; Kite/Gilead: Consultancy; Precision Biosciences: Consultancy; Genmab: Consultancy; Novartis: Consultancy; Spectrum Pharmaceuticals: Consultancy; Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding. Heery: Precision BioSciences: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Arcellx: Current Employment, Current holder of stock options in a privately-held company. List: Halia Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company; CTI Biosciences: Consultancy; Precision BioSciences: Current Employment, Current equity holder in publicly-traded company; Aileron Therapeutics: Consultancy. Johnson: Precision BioSciences, Inc: Current Employment, Current equity holder in publicly-traded company. Lou: Precision BioSciences: Current Employment, Current equity holder in publicly-traded company. Vainorius: Precision BioSciences: Current Employment, Current equity holder in publicly-traded company; Abbvie: Current equity holder in publicly-traded company; United Therapeautics: Current equity holder in publicly-traded company. Olszewski: Genentech, Inc.: Research Funding; TG Therapeutics: Research Funding; PrecisionBio: Research Funding; Celldex Therapeutics: Research Funding; Acrotech Pharma: Research Funding; Genmab: Research Funding. Stein: Amgen: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Stemline: Speakers Bureau. Shah: Adaptive Biotechnologies: Consultancy; Bristol-Myers Squibb/Celgene: Consultancy, Other: Expenses; Novartis: Consultancy, Other: Expenses; Pfizer: Consultancy, Other: Expenses; Amgen: Consultancy; Precision Biosciences: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Other: Expenses, Research Funding; Pharmacyclics/Janssen: Honoraria, Other: Expenses; Acrotech/Spectrum: Honoraria; BeiGene: Consultancy, Honoraria; Incyte: Research Funding; Jazz Pharmaceuticals: Research Funding; Servier Genetics: Other.

OffLabel Disclosure: PBCAR0191 is not FDA approved

*signifies non-member of ASH