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3823 Safety and Efficacy of AUTO1, a Fast-Off Rate CD19 CAR in Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (B-NHL) and Chronic Lymphocytic Leukaemia (CLL)

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Clinical: Poster III
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, Biological therapies, Clinical Practice (Health Services and Quality), CLL, Lymphomas, non-Hodgkin lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Therapies, Lymphoid Malignancies
Monday, December 13, 2021, 6:00 PM-8:00 PM

Claire Roddie, PhD, MD1*, Juliana Dias1*, Maeve A O'Reilly, MBBCHBAO, MD(Res)2, Amaia Cadinanos Garai, BSc MSc1*, Louisa Green, BSc1*, Mahnaz Abbasian1*, Marina Mitsikakou, BSc; MSc1*, Mhairi Vaughan, BSc; MSc1*, Vitoria Meyer Cantinho Pereira, BSc; MSc1*, Maria A V Marzolini3*, Leigh Wood, BA4*, Joanna Olejnik5*, Yenting Ngai, PhD6*, Bilyana Popova, MSc7*, William Wilson5*, Victoria Spanswick3*, Helen Lowe1*, Leah Ensell8*, John A. Hartley, PhD3*, Farzin Farzaneh9*, Mark W. Lowdell, BSc, MSc, PhD, FRCPath10*, David C. Linch11*, Martin Pule, MD, PhD12* and Karl S Peggs, MD, PhD13*

1UCL Cancer Institute, University College London, London, United Kingdom
2Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
3UCL Cancer Institute, London, United Kingdom
4University College Hospital London, london, United Kingdom
5UCL Cancer Trials Centre, London, United Kingdom
6UCL CRUK Cancer Trials Centre, University College London, London, United Kingdom
7CRUK UCL Cancer Trials Centre, UCL, London, United Kingdom
8UCL ECMC GCLP Laboratory, University College London, London, United Kingdom
9King's College London, London, GBR
10Haematology, University College London, London, United Kingdom
11University College London, London, United Kingdom
12Cancer Institute, University College London, London, United Kingdom
13University College London Cancer Institute, UCL Cancer Institute, London, United Kingdom

INTRODUCTION

We have previously described AUTO1, a CD19 CAR with a fast off-rate CD19 binding domain, designed to reduce CAR-T immune toxicity and improve engraftment. Its clinical activity has been tested in r/r paediatric and adult B-ALL. Cumulatively, this data confirms the intended function of the receptor, with low levels of CRS/ICANS and long-term engraftment of CAR T-cells observed in both patient groups. Recently, CAR-T therapy has been explored in indolent lymphomas such as follicular (FL) and mantle cell lymphoma (MCL), but a high incidence of toxicity including Grade 3-4 ICANS has been reported. We have initiated testing of AUTO1 in the setting of indolent and high-grade B-NHL and CLL (NCT02935257).

METHODS

Manufacturing: CAR T-cell products were generated using a semi-automated closed process from non-mobilised leukapheresate.

Study design: Subjects ≥ 16y underwent lymphodepletion with fludarabine (30mg/m2 x3) and cyclophosphamide (60mg/kg x1) prior to AUTO1 infusion, with the exception of the DLBCL cohort who additionally received a single dose of pembrolizumab (200mg) on day -1 to potentiate CAR-T expansion. AUTO1 dose varies based on the indication. Split dosing of 230 x10^6 CD19 CAR T-cells at day 0 and day 9 is employed in the CLL cohort. A single dose of 200 x10^6 CD19 CAR T-cells is delivered to patients with B-NHL. Study endpoints include feasibility of manufacture, grade 3-5 toxicity and remission rates at 1 and 3 months.

RESULTS

As of 17th May 2021, we recruited 13 patients: 7 with FL, 4 with MCL, 1 DLBCL and 1 CLL. Apheresis and product manufacture was successful in all 13 patients and 9 patients were infused: 7 with FL and 2 with MCL. Three patients (1 DLBCL, 1 CLL and 1 MCL) were pending infusion at time of data cut-off and 1 patient (MCL) died due to Covid-19 prior to infusion. Patients treated with AUTO1 had a median age of 56 years (range 39-68y), had received a median of 3 prior lines of treatment (range 2-5) and all patients had stage IV disease at screening. Grade 1 CRS was reported in 4/9 and Grade 2 CRS in 1/9. 1/9 developed MAS which resolved with anakinra/dexamethasone. No ICANS was observed on study. Excellent CAR engraftment was observed and 9/9 patients were in CMR by 18FDG PET-CT post-treatment. At a median of 6.1 months (range 4.0-8.1m), 8/9 patients were disease free at last follow-up. One patient died in CMR at month 5.6 of COVID-19.

CONCLUSION

AUTO1 has a tolerable safety profile in adult patients with r/r B-NHL despite high disease burden. Early data shows 100% complete remission rates and excellent CAR engraftment/expansion. Additional MCL, CLL and DLBCL patients, updated data and longer follow up will be presented.

Disclosures: Roddie: Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy; Gilead: Consultancy, Speakers Bureau. Hartley: Astra Zeneca: Ended employment in the past 24 months; ADC Therapeutics: Consultancy, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Farzaneh: Autolus: Consultancy, Current equity holder in publicly-traded company. Lowdell: Autolus: Consultancy, Current equity holder in publicly-traded company. Linch: Autolus: Consultancy, Current equity holder in publicly-traded company. Pule: Autolus: Current Employment, Current equity holder in publicly-traded company. Peggs: Autolus: Consultancy, Current equity holder in publicly-traded company.

*signifies non-member of ASH