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DRUG:

AUTO1/22

i
Other names: AUTO1/22, AUTO1NG
Associations
Company:
Autolus, BioNTech
Drug class:
CD19-targeted CAR-T immunotherapy, CD22-targeted CAR-T immunotherapy
Related drugs:
Associations
6ms
CARPALL: Immunotherapy With CD19/22 CAR T-cells for CD19+ Haematological Malignancies (clinicaltrials.gov)
P1, N=38, Active, not recruiting, University College, London | Trial completion date: Jan 2032 --> Dec 2036 | Trial primary completion date: Jan 2024 --> Dec 2028
Trial completion date • Trial primary completion date • CAR T-Cell Therapy
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • KMT2A (Lysine Methyltransferase 2A) • IGH (Immunoglobulin Heavy Locus) • CD22 (CD22 Molecule) • TCF3 (Transcription Factor 3)
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cyclophosphamide • fludarabine IV • AUTO1/22
over1year
Transcriptional signatures associated with persisting CD19 CAR-T cells in children with leukemia. (PubMed, Nat Med)
In this study, we systematically analyzed CD19 CAR-T cells of 10 children with R/R B-ALL enrolled in the CARPALL trial via high-throughput single-cell gene expression and T cell receptor sequencing of infusion products and serial blood and bone marrow samples up to 5 years after infusion...Examination of single T cell transcriptomes from a wide range of healthy and diseased tissues across children and adults indicated that the persistence signature may be specific to long-lived CAR-T cells. These findings raise the possibility that a universal transcriptional signature of clinically effective, persistent CD19 CAR-T cells exists.
Journal • CAR T-Cell Therapy • IO biomarker
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
AUTO1/22
over1year
SAFETY AND EFFICACY OF OBECABTAGENE AUTOLEUCEL (OBE-CEL), A FAST-OFF RATE CD19 CAR IN RELAPSED/REFRACTORY ADULT B-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA:TOP LINE RESULTS OF THE PIVOTAL FELIX STUDY (EHA 2023)
Its clinical activity has been tested in r/r paediatric and adult B-ALL trials (CARPALL, Ghorashian S et al., Nat Med 2019; ALLCAR19, Roddie C et al., JCO 2021) and more recently in adults with r/r B-cell malignancies (NCT02935257)...Patients underwent bridging therapy as necessary and lymphodepletion with fludarabine (4x30mg/m2) and cyclophosphamide (2x500mg/m2)... The pre-specified interim analysis of the FELIX study demonstrated that obe-cel for adult r/r B-ALL is safe with low rates of Grade > 3 CRS and/or ICANS, even in patients with high burden disease. Obe-cel is effective with high CR/CRi rates and ongoing CAR T persistence in the majority of responders. The trial has completed dosing of all patients in Cohort A. Additional data and longer follow up will be reported at the conference.
Clinical
|
cyclophosphamide • fludarabine IV • Aucatzyl (obecabtagene autoleucel) • AUTO1/22
over1year
Safety and efficacy of obecabtagene autoleucel (obe-cel, AUTO1), a fast-off rate CD19 CAR, in relapsed/refractory adult B-cell acute lymphoblastic leukemia (r/r B-ALL): Top line results of the pivotal FELIX study. (ASCO 2023)
Its clinical activity has been tested in r/r paediatric and adult B-ALL trials (CARPALL, Ghorashian S et al., Nat Med 2019; ALLCAR19, Roddie C et al., JCO 2021) and more recently in adults with r/r B-cell malignancies (NCT02935257)...Patients underwent bridging therapy as necessary and lymphodepletion with fludarabine (4x30mg/m2) and cyclophosphamide (2x500mg/m2)... The pre-specified interim analysis of the FELIX study demonstrated that obe-cel for adult r/r B-ALL is safe with low rates of Grade >3 CRS and/or ICANS, even in patients with high burden disease. Obe-cel is effective with high CR/CRi rates and ongoing CAR T persistence in the majority of responders. The trial has completed dosing of all patients in Cohort A. Additional data and longer follow up will be reported at the conference.
Clinical
|
cyclophosphamide • fludarabine IV • Aucatzyl (obecabtagene autoleucel) • AUTO1/22
2years
Dual Antigen Targeting with Co-Transduced CD19/22 CAR T Cells May Prevent Antigen-Negative Relapse after CAR T Cell Therapy for Relapsed/Refractory ALL (ASH 2022)
Building on these properties, we developed AUTO1/22 an autologous CAR T cell product co-transduced with two different lentiviral vectors encoding our existing CD19 CAR and a novel CD22CAR designed to recognise targets with low antigen density...Following fludarabine/cyclophosphamide lymphodepletion, patients received 1x106 /kg CAR+ T cells...Six of 12 patients had relapsed post allogeneic SCT, 6 had received prior Blinatumomab/Inotuzumab and 4 had relapsed after prior Tisagenlecleucel...Cytokine release syndrome (CRS) occurred in 11/12 patients (grade 1 n=5, grade 2 n=6) requiring Tocilizumab in 5 cases, but severe (≥ grade 3) CRS was not seen and no patients required ICU admission for CRS... Our data show that dual CD19/22 targeting CAR T cells generated by co-transduction show a favorable safety profile, with robust expansion/persistence and early efficacy in a heavily pre-treated cohort. To date with we have not observed antigen negative relapse. This contrasts to an incidence of 5/6 CD19 negative relapses in the 12 responders treated with single CD19 targeting CAR T cells (AUTO1) in an earlier cohort and suggests dual targeting may be effective in preventing antigen escape.
CAR T-Cell Therapy
|
CD19 (CD19 Molecule) • CD22 (CD22 Molecule) • CD34 (CD34 molecule)
|
cyclophosphamide • Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • Kymriah (tisagenlecleucel-T) • fludarabine IV • Actemra IV (tocilizumab) • Aucatzyl (obecabtagene autoleucel) • AUTO1/22 • AUTO2 • AUTO3
over2years
CARPALL: Immunotherapy With CD19/22 CAR T-cells for CD19+ Haematological Malignancies (clinicaltrials.gov)
P1, N=33, Active, not recruiting, University College, London | Trial completion date: Dec 2030 --> Jan 2032 | Trial primary completion date: Nov 2019 --> Jan 2024
Trial completion date • Trial primary completion date • CAR T-Cell Therapy • IO biomarker
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD19 (CD19 Molecule) • KMT2A (Lysine Methyltransferase 2A) • IGH (Immunoglobulin Heavy Locus) • CD22 (CD22 Molecule) • TCF3 (Transcription Factor 3)
|
KMT2A rearrangement • MLL rearrangement
|
cyclophosphamide • fludarabine IV • AUTO1/22
almost3years
Industrialization of an Academic Miltenyi Prodigy-Based CAR T Process (TCT-ASTCT-CIBMTR 2022)
Clinical testing in two academic studies in r/r paediatric [NCT02443831; CARPALL] and adult B-ALL, B-NHL and B-CLL [NCT02935257; ALLCAR19] confirmed the intended function of the receptor, with low levels of cytokine release syndrome CRS and neurotoxicity and long-term engraftment of CAR T-cells 1,2...CONCLUSION Industrialization of an autologous Miltenyi CAR T process is feasible, leading to a comparable product to that manufactured in an academic setting. We have now opened the pivotal multi-centre phase II part of the FELIX study in r/r adult B-ALL patients.
PD(L)-1 Biomarker • IO biomarker
|
CD19 (CD19 Molecule) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule)
|
PD-1 expression • CD8 positive • CD19 expression
|
Aucatzyl (obecabtagene autoleucel) • AUTO1/22
3years
Industrialization of an Academic Miltenyi Prodigy-Based CAR T Process (ASH 2021)
Clinical testing in two academic studies in relapsed/refractory (r/r) paediatric [ NCT02443831; CARPALL ] and adult B-ALL, B-NHL and B-CLL [NCT02935257; ALLCAR19] confirmed the intended function of the receptor, with low levels of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) and long-term engraftment of CAR T-cells 1,2...CONCLUSION Industrialization of an autologous Miltenyi CAR T process is feasible, leading to a comparable product to that manufactured in an academic setting. We have now opened the pivotal multi-center phase II part of the FELIX study in r/r adult B-ALL patients.
PD(L)-1 Biomarker • IO biomarker
|
CD19 (CD19 Molecule) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule)
|
PD-1 expression • CD8 positive • CD19 expression
|
Aucatzyl (obecabtagene autoleucel) • AUTO1/22
over4years
CARPALL: Immunotherapy With CD19 CAR T-cells for CD19+ Haematological Malignancies (clinicaltrials.gov)
P1, N=32, Active, not recruiting, University College, London | Recruiting --> Active, not recruiting
Enrollment closed • CAR T-Cell Therapy • IO biomarker
|
CD19 (CD19 Molecule) • KMT2A (Lysine Methyltransferase 2A) • IGH (Immunoglobulin Heavy Locus)
|
MLL rearrangement
|
fludarabine IV • AUTO1/22 • cyclophosphamide intravenous