AMG 562

P1, N=10, Terminated, Amgen | Completed --> Terminated; Amgen decided to discontinue study because of a business decision and not because of safety reasons

P1, N=10, Completed, Amgen | Active, not recruiting --> Completed

Blinatumomab is a bispecific T-cell engager (BiTE ® ) construct approved for treatment of relapsed/refractory (r/r) B-cell precursor acute lymphoblastic leukemia (BCP-ALL)...Mimicking the clinical application in an in vitro model system, we showed previously that continuous stimulation (CONT) with AMG 562, a half-life extended CD19xCD3 BiTE ® construct, induces T-cell exhaustion, as seen in chronic infections...In future analyses we will correlate RNA expression levels to functional traits using whole genome co-expression network analysis (WGCNA). Thereby we aim to identify gene clusters critical for persistent T-cell function that might serve as targets to improve efficacy of T-cell based immunotherapies.

As the trial was terminated early, the limited dataset precludes the drawing of any conclusions regarding the safety (maximum tolerated dose/recommended Phase 2 dose) or efficacy of AMG 562. Nevertheless, the study provides proof-of-concept support for use of the HLE BiTE immuno-oncology platform in a variety of hematological malignancies.

P1, N=10, Active, not recruiting, Amgen | Trial completion date: Jun 2021 --> Mar 2022 | Trial primary completion date: Jun 2021 --> Mar 2022

Currently, T cells from patients receiving blinatumomab are being analyzed to confirm the clinical relevance of our findings. Furthermore, RNA-Seq of continuously vs. intermittently AMG 562-exposed T cells will help us to understand underlying transcriptional mechanisms of BiTE® construct induced T-cell exhaustion.

P1, N=10, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting | N=85 --> 10 | Trial completion date: Jul 2024 --> Jun 2021 | Trial primary completion date: Jun 2023 --> Jun 2021