Additional Data Reported for Ongoing Phase I/II AUTO3 Clinical Trials Treating DLBCL

Additional data regarding the ongoing phase I/II clinical trials of the next-generation programmed T-cell therapy, AUTO3, treating adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) was reported by Autolus Therapeutics, the agent’s developer. 

The data was presented at the EHA-EBMT 2nd European CAR T-Cell Meeting, which took place on January 30, 2020 in Barcelona, Spain. The presentation was conducted by Martin Pulé, clinical senior lecturer in the Department of Hematology at UCL Cancer Institute and chief scientific officer of Autolus Therapeutics, in a keynote lecture titled “Improved CAR T-cell approaches for lymphoid malignancies.” 

“The incremental update in the AUTO3 trial presented at the 2nd European CAR T-Cell Meeting continue to support the encouraging early indications of durability and high level of activity previously reported,” Christian Itin, PhD, chairman and chief executive officer of Autolus, said in a press release. “Together with the encouraging signs of a manageable safety profile in adult patients with DLBCL, these early data for AUTO3 show the potential for a differentiated product profile.” 

As of January 21, 2020, the data cut-off date, 18 patients in the ALEXANDER phase I/II clinical trial of AUTO3 were evaluable for safety and efficacy, with a minimum 28-day follow-up. In the cohorts dosed at 450 x 106 AUTO3 cells plus pembrolizumab (Keytruda), 5 out of the 7 patients (ORR = 71%) achieved a response (complete response + partial response) and 4 out of the 7 patients (CRR = 57%) achieved a complete response. 

Across all dose levels, 7 out of 8 complete responders (87%) had ongoing complete responses at a median follow-up of 6 months (range of 1 month to 18 months). Each of the 7 complete responders (100%) treated with AUTO3 in combination with pembrolizumab have ongoing complete responses as of the cut-off date at a median follow-up of 3 months (range of 1 month to 18 months). 

AUTO3 has been generally well tolerated, and no patients have currently experienced dose limiting toxicity. Additionally, there have not been any treatment-related deaths. One patient experienced grade 4 lung infection caused by para-influenza virus that was potentially considered to be related to treatment and the patient is recovering. Infections such as this are a common event in patients with late stage DLBCL according to the researchers.

No patients experiencing grade 3 or higher Cytokine Release Syndrome (CRS) were reported with primary treatment (1 patient experienced grade 3 CRS on retreatment), and 1 of 18 patients experienced a grade 3 neurotoxicity that was quickly resolved with the administration of steroids. Moreover, no patient had experienced neurotoxicity of any grade in cohorts treated with AUTO3 and pembrolizumab as of the data cut-off. 

AUTO3 is the first investigational CAR T-cell therapy that contains 2 independent chimeric antigen receptors targeting CD19 and CD22 that have each been independently designed for single target activity. The agent is designed to minimize relapse caused by single antigen loss in patients with B-cell malignancies. 

AUTO3 is currently being tested in adult patients with DLBCL in the ALEXANDER trial and in pediatric acute lymphoblastic leukemia in the AMELIA clinical trial. 

Reference:

Autolus Therapeutics Presents Encouraging Additional Data Showcasing Clinical Progress of Programmed T Cell Therapy Pipeline in Blood Cancers [news release]. London, England. Published January 30, 2020. morningstar.com/news/globe-newswire/7807712/autolus-therapeutics-presents-encouraging-additional-data-showcasing-clinical-progress-of-programmed-t-cell-therapy-pipeline-in-blood-cancers. Accessed January 31, 2020.