ALLCAR19: UPDATED DATA USING AUTO1, A NOVEL FAST-OFF RATE CD 19 CAR IN RELAPSED /REFRACTORY B-ACUTE LYMPHOBLASTIC LEUKAEMIA
Author(s): ,
Claire Roddie
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
,
Maeve O'Reilly
Affiliations:
University College London Hospitals,London,United Kingdom
,
Maria Marzolini
Affiliations:
University College London Hospitals,London,United Kingdom
,
Leigh Wood
Affiliations:
University College London Hospitals,London,United Kingdom
,
Juliana Dias
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
,
Mahnaz Abbasian
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
,
Ketki Vispute
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
,
Mark Lowdell
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
,
Graham Wheeler
Affiliations:
University College London,London,United Kingdom
,
Joanna Olejnik
Affiliations:
University College London,London,United Kingdom
,
Bilyana Popova
Affiliations:
University College London,London,United Kingdom
,
Kim Champion
Affiliations:
University College London,London,United Kingdom
,
Alexia Gali
Affiliations:
University College London,London,United Kingdom
,
Yashma Pathak
Affiliations:
University College London,London,United Kingdom
,
Victoria Spanswick
Affiliations:
University College London,London,United Kingdom
,
Helen Lowe
Affiliations:
University College London,London,United Kingdom
,
John Hartley
Affiliations:
University College London,London,United Kingdom
,
Farhatullah Syed
Affiliations:
Institute of Child Health,London,United Kingdom
,
Wasim Qasim
Affiliations:
Institute of Child Health,London,United Kingdom
,
Farzin Farzaneh
Affiliations:
King's College London,London,United Kingdom
,
David Linch
Affiliations:
University College London,London,United Kingdom
,
Martin Pule
Affiliations:
University College London,London,United Kingdom
Karl Peggs
Affiliations:
University College London,London,United Kingdom
(Abstract release date: 05/14/20) EHA Library. Roddie C. 06/12/20; 294939; S119
Claire Roddie
Claire Roddie
Contributions
Abstract

Abstract: S119

Type: Oral Presentation

Session title: Cellular, antibody and targeted therapy

Background
In adults, Prognosis for B-ALL is poor and there is currently no CD19 CAR therapeutic with acceptable toxicity and durable efficacy. We developed a novel second generation CD19CAR (CAT-41BBz CAR) with a faster off-rate but equivalent on-rate to the FMC63-41BBz CAR, designed to result in more physiological T-cell activation, reduce toxicity and improve engraftment.

Aims
We describe updated data from the Phase I ALLCAR19 (NCT02935257) study of AUTO1 in r/r adult B-ALL.

Methods
Manufacturing: AUTO1 utilises non-mobilised autologus leucapheresate. The first 6 products were generated using a standard dynabead/WAVE bioreactor process and subsequent products using a semi-automated closed process.

Study design: subjects 16-65y underwent lymphodepletion with fludarabine (30mg/m2 x3) and cyclophosphamide (60mg/kg x1) followed by split dose CAR T-cell infusion (Day 0: if>/=20% BM blasts, infuse 10 x106 CAR T-cells; if <20% BM blasts, 100 x106 CAR T-cells. At Day+9: if no grade 3-5 CRS/CRES, infuse Dose 2, to a total dose of 410 x106 CAR T-cells). Study endpoints include feasibility of manufacture, grade 3-5 toxicity and remission rates at 1 and 3 months.

Results
As of 25 Nov 2019, 20 patients have been leukapheresed, 19 products manufactured and 16 patients received at least 1 dose of AUTO1. The median age was 35.5y (range 18-58), 69% had prior blinatumomab or inotuzumab ozogamicin and 75% had prior HSCT. At the time of pre-conditioning, 46% had >/=50% BM blasts.

No patients experienced >/=Grade 3 CRS (Lee criteria), 3/16 (19%) experienced Grade 3 CRES that swiftly resolved with steroids. Of 15 patients evaluable for efficacy, 87% achieved MRD negative CR. Curently 5 patients have died but 10/15 remain on study and continue in MRD negative remission with a median follow up of 11 months (range 0.5-21). For all treated patients, the EFS at 6months was 68% and for the 10 patients treated with the closed process, the EFS at 6 months was 100%. All patients had robust CAR expansion (mean peak CAR T levels 111,239 copies/ug DNA) and all responding patients had ongoing CAR T-cell persistence at last follow up. Only one patient has received HSCT post AUTO1.

Conclusion
AUTO1 has a tolerable safey profile in adult patients with r/r B-ALL despite high disease burden. Early data shows high remission rates with 87% achieving MRD negative CR and in patients treated with the closed process, the EFS at 6months is 100%. This preliminary data supports the further development of AUTO1 as a stand-alone treatment in patients with r/r B-ALL. Data from addiitonal patients and more follow up will be presented.

Session topic: 02. Acute lymphoblastic leukemia - Clinical

Keyword(s): Acute lymphoblastic leukemia, Adult, CAR-T

Abstract: S119

Type: Oral Presentation

Session title: Cellular, antibody and targeted therapy

Background
In adults, Prognosis for B-ALL is poor and there is currently no CD19 CAR therapeutic with acceptable toxicity and durable efficacy. We developed a novel second generation CD19CAR (CAT-41BBz CAR) with a faster off-rate but equivalent on-rate to the FMC63-41BBz CAR, designed to result in more physiological T-cell activation, reduce toxicity and improve engraftment.

Aims
We describe updated data from the Phase I ALLCAR19 (NCT02935257) study of AUTO1 in r/r adult B-ALL.

Methods
Manufacturing: AUTO1 utilises non-mobilised autologus leucapheresate. The first 6 products were generated using a standard dynabead/WAVE bioreactor process and subsequent products using a semi-automated closed process.

Study design: subjects 16-65y underwent lymphodepletion with fludarabine (30mg/m2 x3) and cyclophosphamide (60mg/kg x1) followed by split dose CAR T-cell infusion (Day 0: if>/=20% BM blasts, infuse 10 x106 CAR T-cells; if <20% BM blasts, 100 x106 CAR T-cells. At Day+9: if no grade 3-5 CRS/CRES, infuse Dose 2, to a total dose of 410 x106 CAR T-cells). Study endpoints include feasibility of manufacture, grade 3-5 toxicity and remission rates at 1 and 3 months.

Results
As of 25 Nov 2019, 20 patients have been leukapheresed, 19 products manufactured and 16 patients received at least 1 dose of AUTO1. The median age was 35.5y (range 18-58), 69% had prior blinatumomab or inotuzumab ozogamicin and 75% had prior HSCT. At the time of pre-conditioning, 46% had >/=50% BM blasts.

No patients experienced >/=Grade 3 CRS (Lee criteria), 3/16 (19%) experienced Grade 3 CRES that swiftly resolved with steroids. Of 15 patients evaluable for efficacy, 87% achieved MRD negative CR. Curently 5 patients have died but 10/15 remain on study and continue in MRD negative remission with a median follow up of 11 months (range 0.5-21). For all treated patients, the EFS at 6months was 68% and for the 10 patients treated with the closed process, the EFS at 6 months was 100%. All patients had robust CAR expansion (mean peak CAR T levels 111,239 copies/ug DNA) and all responding patients had ongoing CAR T-cell persistence at last follow up. Only one patient has received HSCT post AUTO1.

Conclusion
AUTO1 has a tolerable safey profile in adult patients with r/r B-ALL despite high disease burden. Early data shows high remission rates with 87% achieving MRD negative CR and in patients treated with the closed process, the EFS at 6months is 100%. This preliminary data supports the further development of AUTO1 as a stand-alone treatment in patients with r/r B-ALL. Data from addiitonal patients and more follow up will be presented.

Session topic: 02. Acute lymphoblastic leukemia - Clinical

Keyword(s): Acute lymphoblastic leukemia, Adult, CAR-T

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