dm+d

Unassigned

New Medicines

Acute lymphoblastic leukaemia (ALL) in adults

Information

New molecular entity
Autolus
Autolus

Development and Regulatory status

Phase II Clinical Trials
None
Phase II Clinical Trials
Yes
Apr 20FDA accepts the Investigational New Drug (IND) application for AUTO 1 for the treatment of adults with ALL. The IND allows initiation of the first pivotal study, AUTO1-AL1 in the US [3].
Nov 19Granted orphan drug status in US for treatment of ALL (precursor cell lymphoblastic leukaemia lymphoma) [3].

Category

CD19-targeting CAR T cell therapy with fast target binding off-rate designed to minimize excessive activation and associated cytokine release, which may reduce toxicity. In addition, the fast off-rate may reduce T cell exhaustion and enhance persistence.
Global incidence is about 3 per 100,000 population, with about 3 out of 4 cases occurring in children aged under 6 years. ALL represents 12% of all leukaemia (but 80% in children) [1].
Acute lymphoblastic leukaemia (ALL) in adults
Intravenous

Trial or other data

Nov 20PI/II AUTO1-AL1 (NCT04404660) is recruiting [2].
Nov 20Autolus expects to announce long-term data from the PI ALLCAR19 trial at ESMO [5].
Mar 20Autolous announces data from the PI ALLCAR19 trial (NCT02935257). As of the most recent cut-off date of November 25, 2019, of the 15 patients evaluable for efficacy, 13 patients (87%) achieved minimal residual disease, or MRD, negative complete responses at one month and all patients had ongoing CAR T cell persistence at last follow-up. 10 of the 15 evaluable patients (67%) remain disease-free at a median follow up of 11 months (range of 0.5 month - 21 months). Of the 16 patients dosed, ten patients were dosed with AUTO1 manufactured using our semi-automated, fully enclosed system for manufacturing. In this cohort, nine patients were evaluable and achieved MRD negative complete responses of 100%. The median follow-up in this cohort was 6.7 months (range of 1.1 month-14.5 months). The event free survival or EFS and overall survival or OS data are preliminary considering the small number of patients [4].
Mar 20Pivotal PI/II trial to evaluate AUTO 1 in adults with ALL who have previously been treated and subsequently progressed starts (AUTO1-AL1; NCT04404660). 145 patients will be enrolled in the US and UK (University College London Hospitals, Kings College Hospital in London, Manchester Royal Infirmary, Queen Elizabeth University Hospital in Glasgow, Freeman Hospital in Newcastle upon Tyne, University Hospitals Bristol and Weston NHS Foundation Trust). Primary outcome is overall response rate and safety; collection of these data is due to complete Mar 23 [2].

Acute lymphoblastic leukaemia (ALL) in children

Information

Licence extension / variation
Autolus
Autolus

Development and Regulatory status

Phase I Clinical Trials
None
None
Yes
Nov 19Granted orphan drug status in US for treatment of ALL (precursor cell lymphoblastic leukaemia lymphoma) [3].

Category

CD19-targeting CAR T cell therapy with fast target binding off-rate designed to minimize excessive activation and associated cytokine release, which may reduce toxicity. In addition, the fast off-rate may reduce T cell exhaustion and enhance persistence.
Global incidence is about 3 per 100,000 population, with about 3 out of 4 cases occurring in children aged under 6 years. ALL represents 12% of all leukaemia (but 80% in children) [1].
Acute lymphoblastic leukaemia (ALL) in children
Intravenous

Trial or other data

Nov 20PI CARPALL trial is active but has finished recruitment [2].
Nov 19Results announced from PI CARPALL trial. 19 out of 21 treated patients (90%) achieved molecular complete remission at one month post infusion. CAR T cell expansion was excellent and was detectable by flow in a number of patients up to 36 months. Persistence was noted in 15 of 21 patients at last follow-up, up to 36 months. In cohort 2, 100% of patients achieved molecular complete remission at one month post infusion. In the 14 patients in cohort 1, the overall survival at six months was 86% and at 12 months was 71%; event free survival at six months was 71% and at 12 months was 54%. The patients in cohort 2 were not evaluable for these parameters. Overall, eight patients relapsed; five of eight evaluable relapses were due to loss of CD19 antigen on the tumor cells [3,4].
Apr 16PI CARPALL trial to evaluate the safety, efficacy and duration of response of AUTO1 in children and young adults with CD19+ haematological malignancies, including ALL (precursor cell lymphoblastic leukaemia lymphoma) and Burkitt lymphoma starts (UCL 14/0529; NCT02443831). 32 patients aged up to 24 years will be recruited in the UK (at Great Ormond Street Hospital, University College Hospital in London, Royal Manchester Infirmary, and Royal Manchester Royal Children´s Hospital). Primary outcomes are toxicity and molecular remission; collection of these data are due to complete Nov 19 [2].