dm+d

Unassigned

New Medicines

Relapsed or refractory diffuse large B-cell lymphoma (DLBCL)

Information

New molecular entity
Autolus
Autolus

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase II Clinical Trials
Mar 20Autolous report they will take a go/no go decision on PII initiation of AUTO3 in DLBCL in mid-2020 [7].

Category

An autologous, dual targeting CAR-T cell candidate which targets CD19 and CD22 antigens of cancer cells
The overall annual incidence of DLBCL in Europe is 3.8 per 100,000 but the incidence increases with age and varies considerably across Europe [1].
Relapsed or refractory diffuse large B-cell lymphoma (DLBCL)
Intravenous infusion

Trial or other data

Nov 20Autolus reports that it continues to enrol in the AUTO3 ALEXANDER outpatient cohort. Updated data including longer term follow up will be presented in oral presentations at the American Society of Hematology (ASH) in Dec 20 [9].
Sep 20PI/II ALEXANDER study is still recruiting, including at The Beatson West of Scotland Cancer Centre / Queen Elizabeth University Hospital in Glasgow, University College London Hospitals NHS Foundation Trust, Manchester University NHS Foundation Trust and at the Freeman Hospital, Newcastle upon Tyne. Timescales unchanged [6].
Dec 19NCT03287817 UK sites- UCL, Manchester, Newcastle [3]
Dec 19Autolus announces data from the PI/II ALEXANDER trial highlighting progress on AUTO3, the first-in-human bicistronic CD19 and CD22 CAR, in patients with relapsed/refractory DLBCL. The trial is divided into a phase 1 safety cohort and a phase 2 efficacy cohort, and is designed to assess safety (incidence of ≥ Grade 3 toxicity occurring within 75 days of AUTO3 infusion) and other primary and secondary endpoints including overall response and other safety, efficacy and product generation measures. In the dose escalation phase, 16 patients were treated, with 4 patients dosed at 50 x 106 cells without pembrolizumab; 11 patients were dosed at escalating doses of AUTO3 with pembrolizumab administered at day 14 as follows: 3 at 50 x 106 cells, 4 at 150 x 106 cells, and 4 at 450 x 106 of AUTO3; and 1 patient was dosed with 450 x 106 cells with pembrolizumab administered 1 day before AUTO3 infusion. Fourteen patients were evaluable at one month. AUTO3 was well-tolerated, with no patients experiencing ≥ Grade 3 cytokine release syndrome (CRS) with primary infusion and 1 of 14 experiencing Grade 3 neurotoxicity that resolved swiftly with steroids. There were no pembrolizumab immune-related toxicities and the majority of grade 3 or higher adverse events were hematological. Low levels of serum cytokines are consistent with the observed low levels of CRS and neurotoxicity. Across all tested doses 5 patients achieved a complete response, with 4 of 5 complete responses ongoing, the longest at 18 months. All CRs were achieved without need for steroid or tocilizumab-based management of the patients or ICU level care [5].
Dec 19Another PII trial due to start 2Q 20 [4]
Jan 19PI/II ALEXANDER trial is recruiting [2].
Jun 17PI/II ALEXANDER trial for the investigation of safety and clinical activity of AUTO 3 in patients with relapsed or refractory DLBCL starts (NCT03287817; AUTO3-DB1). The open-label trial intends to enrol approximately 120 patients in the UK, Germany, Netherlands and the US. Collection of primary outcome data is due to complete Mar 21 [2].

Relapsed or refractory B-cell acute lymphoblastic leukaemia (ALL) - in young adults and children

Information

New molecular entity
Autolus
Autolus

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase II Clinical Trials
Yes
Nov 20AUTO3 for paediatric ALL is no longer listed in company pipeline, or discussed in any quarterly/annual reports in 2020. Development plans unclear. Autolus may have decided to focus on AUTO1/22 for this patient group [7].
Apr 19US FDA grants orphan drug designation to AUTO 3 for treatment of precursor cell lymphoblastic leukaemia-lymphoma (acute lymphoblastic leukaemia) [3].

Category

An autologous, dual targeting CAR-T cell candidate which targets CD19 and CD22 antigens of cancer cells
ALL is the most common cancer in children. Global incidence is about 3 per 100,000 population, with about 3 out of 4 cases occurring in children aged under 6 years [1].
Relapsed or refractory B-cell acute lymphoblastic leukaemia (ALL) - in young adults and children
Intravenous infusion

Trial or other data

Nov 20Results for the PI/II AMELIA study submitted to the clinicaltrials.gov website, after it completed in May 20 [6].
Dec 19NCT03289455 - UK sites Great Ormond Street, UCL, Manchester Children´s
Dec 19Autolus announces data for AUTO3 in paediatric ALL. The AMELIA study recruited a total of 18 patients to the active dose (≥ 3 x 106 /kg) cohorts, and product was manufactured successfully for 14 of the 15 patients (93%) who underwent leukapheresis. Eleven patients were treated with AUTO3, manufactured using a semi-automated closed manufacturing process. Ten of 11 patients were CAR T cell-naive, while 1 had previously received CAR T cell therapy. AUTO3 was well-tolerated overall, with no patients experiencing ≥ Grade 3 CRS and no patients experiencing ≥ Grade 2 neurotoxicity, in doses ≥3x106 /kg CAR-T cells. No AUTO3-related deaths were reported. Among the 10 CAR T-naïve patients, at a median follow-up time of 9.7 months (range 1.8- 18), 9 of 10 patients (90%) achieved a complete response, and 8 of 10 (80%) achieved complete molecular remission by PCR. Estimated overall survival at 12 months was 100%. There are 2 ongoing patients in complete molecular remission at 12 and 15 months post-AUTO3 infusion, respectively. The most common cause of relapse was due to loss of CAR T-cell persistence. The median persistence of CAR-T cells in blood was 170 days [5].
Jul 18PI/II AMELIA study is recruiting [2].
Jun 17PI/II AMELIA trial to evaluate safety and clinical activity of AUTO 3 in paediatric, adolescent and adult patients with relapsed or refractory precursor B-cell ALL starts (NCT03289455; AUTO3-PA1). 54 patients will be recruited in the UK, Europe and the US. The phase 2 portion of the study is expected to start in the H2 2019. Collection of primary outcome data is due to complete Dec 21 [2].