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DRUG:

Aucatzyl (obecabtagene autoleucel)

i
Other names: CD19 CAR T-cells, obe-cel, CAT19, AUTO1, CD19CAT-41BBZ CAR T-cells, AUTO 1
Company:
Autolus
Drug class:
CD19-targeted CAR-T immunotherapy
Related drugs:
2ms
Obecabtagene autoleucel (obe-cel) for Adult Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL): Deep Molecular Remission May Predict Better Outcomes (ASH 2024)
Conclusions : Eighty-four percent of responders to obe-cel for whom MRD by NGS could be analyzed achieved MRD <10‾6 leukemic cells which was associated with more durable responses, and higher EFS and OS rates than those observed in pts with MRD ≥10‾4 and between 10‾4 and 10‾6 leukemic cells. Pts who did not achieve MRD <10‾6 had poorer outcomes.
Clinical
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clonoSEQ
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Aucatzyl (obecabtagene autoleucel)
9ms
New P1 trial • CAR T-Cell Therapy
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cyclophosphamide • Aucatzyl (obecabtagene autoleucel)
1year
Delivery of Obecabtagene Autoleucel (obe-cel, AUTO1) for the FELIX Pivotal Study Demonstrating Robust Cell Processing, Robust Release Testing, and Reliable Logistics, Together with Readiness for Sustainable Patient (pt) Care (ASH 2023)
The FELIX study successfully demonstrated the robust operability of obe-cel manufacturing, QC and logistics processes, meeting target V2C and V2D. All apheresis starting material successfully processed despite the multitude of constraints posed by the COVID-19 pandemic. Further optimization and improvements made during the study increased reliability, consistency and precision of the manufacturing process, and supported the development of a new obe-cel manufacturing facility with greater production capacity that aims to achieve a ≥95% manufacturing success rate with ≤15-day V2C times.
Clinical
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Aucatzyl (obecabtagene autoleucel)
over1year
AKT inhibition generates potent polyfunctional clinical grade AUTO1 CAR T-cells, enhancing function and survival. (PubMed, J Immunother Cancer)
Ultimately, AUTO1 generated with VIII may begin to overcome the product specific factors contributing to CD19+relapse.
Journal • CAR T-Cell Therapy
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Aucatzyl (obecabtagene autoleucel)
over1year
CAR T-Cell Therapy • Trial primary completion date
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CD19 positive
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clonoSEQ
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cyclophosphamide • Aucatzyl (obecabtagene autoleucel)
over1year
CAROUSEL: Immunotherapy Using CAR T-cells to Target CD19 for Relapsed/Refractory CD19+ Primary CNS Lymphoma (clinicaltrials.gov)
P1, N=12, Active, not recruiting, University College, London | Recruiting --> Active, not recruiting
Enrollment closed • CAR T-Cell Therapy
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Aucatzyl (obecabtagene autoleucel)
over1year
CAR T-Cell Therapy • Enrollment closed
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CD19 positive
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clonoSEQ
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cyclophosphamide • Aucatzyl (obecabtagene autoleucel)
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
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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
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cyclophosphamide • fludarabine IV • Aucatzyl (obecabtagene autoleucel) • AUTO1/22
over1year
Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR. (PubMed, Mol Ther)
CAT/9A8 CART eliminated single and double positive target cells in vitro and eliminated CD19 tumours in vivo. CAT/9A8 CART is being tested in a phase I clinical study NCT02443831.
Journal
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CD19 (CD19 Molecule) • CD22 (CD22 Molecule)
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Aucatzyl (obecabtagene autoleucel)
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
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CD19 (CD19 Molecule) • CD22 (CD22 Molecule) • CD34 (CD34 molecule)
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cyclophosphamide • Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • Kymriah (tisagenlecleucel-T) • fludarabine IV • Actemra IV (tocilizumab) • Aucatzyl (obecabtagene autoleucel) • AUTO1/22 • AUTO2 • AUTO3
2years
Safety, Efficiency and Long-Term Follow-up of AUTO1, a Fast-Off Rate CD19 CAR in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukaemia and Other B-Cell Malignancies (ASH 2022)
Study design: Subjects ≥ 16y received fludarabine (30mg/m2 x3) and cyclophosphamide (60mg/kg x1) conditioning. DLBCL patients additionally received pembrolizumab (200mg) on day -1... AUTO1 has a tolerable safety profile in patients with r/r B-cell cancers despite high disease burden. In the B-ALL cohort, long-term follow-up indicates that 40% of patients continue in remission post-AUTO1. In both indolent and aggressive NHL and in CLL, AUTO1 shows excellent ORR and CAR engraftment/persistence.
Clinical
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CD19 (CD19 Molecule)
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Keytruda (pembrolizumab) • cyclophosphamide • fludarabine IV • Aucatzyl (obecabtagene autoleucel)
over2years
Trial completion date • Trial primary completion date • CAR T-Cell Therapy
|
CD19 (CD19 Molecule)
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Aucatzyl (obecabtagene autoleucel)
over2years
FELIX: A Study of CD19 Targeted CAR T Cell Therapy in Adult Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukaemia (ALL) (clinicaltrials.gov)
P1/2; Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Mar 2023 --> Jun 2023
CAR T-Cell Therapy • Trial completion date • Trial primary completion date
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CD19 (CD19 Molecule)
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CD19 positive
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clonoSEQ
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cyclophosphamide • Aucatzyl (obecabtagene autoleucel)
over2years
SAFETY AND EFFICACY FINDINGS OF AUTO1, A FAST-OFF RATE CD19 CAR, IN RELAPSED/REFRACTORY B-CELL NON-HODGKIN'S LYMPHOMA (B-NHL), AND CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) / SMALL LYMPHOCYTIC LYMPHOMA (SLL) (EHA 2022)
Study design: Subjects ≥ 16y underwent lymphodepletion with fludarabine (30mg/m 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...Early data shows excellent complete remission rates and excellent CAR engraftment/expansion. Additional patients, updated data and longer follow up will be presented.
Clinical
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CD19 (CD19 Molecule)
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Keytruda (pembrolizumab) • cyclophosphamide • fludarabine IV • Aucatzyl (obecabtagene autoleucel)
over2years
SAFETY AND EFFICACY FINDINGS OF AUTO1, A FAST-OFF RATE CD19 CAR, IN RELAPSED/REFRACTORY PRIMARY CNS LYMPHOMA (EHA 2022)
Study Design: Subjects>/=16y underwent lymphodepletion with fludarabine (Flu;30mg/m2x3) and cyclophosphamide (Cy;60mg/kgx1) and Pembrolizumab (200mgx1) prior to IV AUTO1 infusion (250x10^6 CAR-T)...I-VEN administration was well-tolerated and AUTO1 demonstrated activity via direct CSF infusion in a patient who failed IV therapy. Additional patients, updated biological data and longer follow-up will be presented.
Clinical
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CD19 (CD19 Molecule)
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Keytruda (pembrolizumab) • cyclophosphamide • fludarabine IV • Aucatzyl (obecabtagene autoleucel)
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
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CD19 (CD19 Molecule) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule)
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PD-1 expression • CD8 positive • CD19 expression
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Aucatzyl (obecabtagene autoleucel) • AUTO1/22
3years
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) (ASH 2021)
Study design: Subjects ≥ 16y underwent lymphodepletion with fludarabine (30mg/m 2 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...1/9 developed MAS which resolved with anakinra/dexamethasone...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.
Clinical
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CD19 (CD19 Molecule)
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Keytruda (pembrolizumab) • cyclophosphamide • dexamethasone • fludarabine IV • Aucatzyl (obecabtagene autoleucel) • Kineret (anakinra)
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
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CD19 (CD19 Molecule) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule)
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PD-1 expression • CD8 positive • CD19 expression
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Aucatzyl (obecabtagene autoleucel) • AUTO1/22
over3years
Durable Responses and Low Toxicity After Fast Off-Rate CD19 Chimeric Antigen Receptor-T Therapy in Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia. (PubMed, J Clin Oncol)
AUTO1 demonstrates a tolerable safety profile, high remission rates, and excellent persistence in r/r adult B-ALL. Preliminary data support further development of AUTO1 as a stand-alone treatment for r/r adult B-ALL.
Clinical • Journal
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CD19 (CD19 Molecule)
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Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • Aucatzyl (obecabtagene autoleucel)
over3years
CAROUSEL: Immunotherapy Using CAR T-cells to Target CD19 for Relapsed/Refractory CD19+ Primary CNS Lymphoma (clinicaltrials.gov)
P1, N=12, Recruiting, University College, London | Not yet recruiting --> Recruiting
Enrollment open • CAR T-Cell Therapy
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CD19 (CD19 Molecule)
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Aucatzyl (obecabtagene autoleucel)
4years
CAROUSEL: Immunotherapy Using CAR T-cells to Target CD19 for Relapsed/Refractory CD19+ Primary CNS Lymphoma (clinicaltrials.gov)
P1, N=12, Not yet recruiting, University College, London | Initiation date: Nov 2020 --> Feb 2021
Trial initiation date • CAR T-Cell Therapy
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CD19 (CD19 Molecule)
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Aucatzyl (obecabtagene autoleucel)
4years
Enrollment open • CAR T-Cell Therapy
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CD19 (CD19 Molecule)
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Aucatzyl (obecabtagene autoleucel)