– Initial results were presented from ongoing Phase 1/2 trials in pediatric acute lymphoblastic leukemia (AMELIA trial) and diffuse B cell lymphoma (ALEXANDER trial) –
Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, today highlighted updated results from its ongoing Phase 1/2 AMELIA clinical trial of AUTO3 in patients with relapsed/refractory pediatric acute lymphoblastic leukemia (pALL) and its ongoing Phase 1/2 ALEXANDER clinical trial in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) presented at the 60th American Society of Hematology (ASH) Annual Meeting, San Diego, California. AUTO3 is a dual-targeted therapy incorporating two separate chimeric antigen receptors (CARs). Observations from preclinical studies indicate that AUTO3 independently targets CD19 and CD22. AUTO3 is designed to reduce relapse driven by antigen loss, a key defense mechanism used by the tumor cells and the primary cause of relapse in pALL.
“The preliminary results of the AMELIA trial indicate that AUTO3, the first dual targeting CD19 and CD22 CAR T cell therapy under development for pediatric ALL, appears to have a manageable safety profile, with the potential to overcome target-negative relapse, a major limitation of current CD19-targeted therapies,” said Professor Persis Amrolia, lead investigator and Consultant in Bone Marrow Transplant at Great Ormond Street Hospital (GOSH) and NIHR Research Professor of Transplantation Immunology at UCL Great Ormond Street Institute of Child Health (ICH).
“In the ALEXANDER trial, preliminary results indicate that AUTO3 followed by consolidation with a limited duration of anti-PD1 therapy appears to have a manageable safety profile at the doses evaluated. This is the first therapy that aims to address two emerging resistance mechanisms for non-Hodgkin lymphoma, target-negative relapse and checkpoint upregulation,” said Dr. Anas Younes, Chief, Lymphoma Service at Memorial Sloan Kettering Cancer Center.
Simultaneous Targeting of CD19 and CD22: Phase 1 Trial of AUTO3, a Bicistronic Chimeric Antigen Receptor (CAR) T-cell Therapy, in Pediatric Patients with Relapse/Refractory B-cell Acute Lymphoblastic Leukemia (r/r B-ALL): AMELIA Trial (Abstract Number 279, oral presentation at 8:00AM on Sunday, December 2, 2018)
Dr. Amrolia reported on 10 patients with relapsed or refractory ALL who received an AUTO3 infusion as a single dose or split dose dependent on their tumor burden. Key inclusion criteria included age 1-24 years old with relapsed or refractory B-lineage ALL at high risk in first relapse or in second or greater relapse. Prior targeted therapies to CD19 and CD22 were not excluded. The average age of the 10 evaluable patients was 8.5 years, the median number of prior lines of therapy was 3. Product was successfully manufactured for all patients. AUTO3 was generally well tolerated with no ≥ Grade 3 CRS, no ICU admission, and no pressors or critical care support for CRS required. One case of Grade 3 neurotoxicity was observed which was considered unlikely related to AUTO3 and primarily attributed to prior intrathecal chemotherapy. Grade 3 or higher cytopenias lasting at least 30 days were noted in 4 out of 10 patients. Among the 10 evaluable patients at all dose levels, 8 out of 10 achieved MRD negative CR and higher response rates were observed at doses ≥3 x106/kg dose levels with all patients achieving MRD-negative remission. In the higher dose group, 4 out of 6 (67%) patients have an ongoing molecular CR and importantly, no loss of CD19 or CD22 was noted among relapsed patients. Initial data indicates response rates and persistence are dose dependant. Dose escalation is ongoing.
For more information about this trial and the inclusion criteria, visit www.ClinicalTrials.gov(NCT03289455).
Trial of AUTO3, the First Bicistronic Chimeric Antigen Receptor (CAR) Targeting CD19 and CD22, Followed By Anti-PD1 Consolidation in Patients with Relapsed/Refractory (r/r) Diffuse Large B Cell Lymphoma (DLBCL): Alexander Trial (Abstract Number 1679, poster presentation from 6:15 PM – 8:15PM on Saturday, December 1, 2018)
Dr. Kirit Ardeshna, principal investigator at University College London, UK, reported preliminary clinical data on safety and efficacy from this open-label, multi‑center trial in patients with DLBCL treated with a single dose of AUTO3 followed by consolidation with anti-PD-1 antibody (pembrolizumab). Key inclusion criteria included histologically confirmed DLBCL, chemotherapy-refractory disease or relapse after at least two lines of therapy or after ASCT, and no prior allogeneic stem cell transplant. There were 7 patients evaluable for safety with at least 28 day follow up post-treatment. The median number of prior lines of therapy in these 7 evaluable patients was 3 (range was 2 to 4). All patients were treated at the starting dose of 50×106 transformed CAR T cells. Three patients received a consolidation with pembrolizumab, and 4 patients did not receive treatment with pembrolizumab. None of the treated patients developed CRS grade 3 or higher and one patient had neurotoxicity grade 3, considered possibly related to AUTO3. No dose limiting toxicities were observed and dose escalation continues. Six patients were evaluable for response, two achieved a CR and two a PR; two patients did not respond. The two CRs were ongoing at six and three months, respectively.
For more information about this trial and the inclusion criteria, visit:
www.ClinicalTrials.gov(NCT03287817).
