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.
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.
over 1 year ago
Clinical
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cyclophosphamide • fludarabine IV • Aucatzyl (obecabtagene autoleucel) • AUTO1/22
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.
over 1 year ago
Clinical
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cyclophosphamide • fludarabine IV • Aucatzyl (obecabtagene autoleucel) • AUTO1/22
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.
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.
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.
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.
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 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.
almost 3 years ago
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)
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 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.
3 years ago
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)
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.