- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, AMG 562 / Amgen
Journal: T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals. (Pubmed Central) - Sep 14, 2022
In an in vitro model system, mimicking 28-day continuous infusion with the half-life-extended CD19xCD3 bispecific AMG 562, we identified hallmark features of exhaustion arising over time...Our data demonstrate the relevance of T-cell exhaustion in bispecific antibody therapy and highlight that T cells can be functionally and transcriptionally rejuvenated with TFIs. In view of the growing number of bispecific molecules being evaluated in clinical trials, our findings emphasize the need to consider and evaluate TFIs in application schedules to improve clinical outcomes.
- |||||||||| AMG 562 / Amgen
Trial completion: Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 562 in Subjects With r/r Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma (clinicaltrials.gov) - Feb 23, 2022
P1, N=10, Completed,
In view of the growing number of bispecific molecules being evaluated in clinical trials, our findings emphasize the need to consider and evaluate TFIs in application schedules to improve clinical outcomes. Active, not recruiting --> Completed
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, AMG 562 / Amgen
Treatment-Free Intervals during CD19xCD3 BiTE® Construct-Mediated T-Cell Stimulation Induce Functional Reinvigoration and Transcriptional Reprogramming of Exhausted T Cells (GWCC - B216-B217, Level 2) - Nov 5, 2021 - Abstract #ASH2021ASH_1945;
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.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, AMG 562 / Amgen
Reduction of CD19-BiTE® construct-induced T-cell exhaustion through breaks in treatment (A7) - Sep 20, 2021 - Abstract #DGHO2021DGHO_63;
Our results demonstrate that continuous BiTE ® construct exposure leads to T-cell exhaustion which can be ameliorated through TFI. Currently, T cells from patients blinatumomab are being receiving analyzed to confirm the clinical relevance of our findings.
- |||||||||| AMG 562 / Amgen
Trial completion date, Trial primary completion date: Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 562 in Subjects With r/r Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma (clinicaltrials.gov) - Jan 31, 2021
P1, N=10, Active, not recruiting,
Nevertheless, the study provides proof-of-concept support for use of the HLE BiTE immuno-oncology platform in a variety of hematological malignancies. Trial completion date: Jun 2021 --> Mar 2022 | Trial primary completion date: Jun 2021 --> Mar 2022
- |||||||||| AMG 562 / Amgen
Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date: Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 562 in Subjects With r/r Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma (clinicaltrials.gov) - Aug 8, 2020
P1, N=10, Active, not recruiting,
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. Recruiting --> Active, not recruiting | N=85 --> 10 | Trial completion date: Jul 2024 --> Jun 2021 | Trial primary completion date: Jun 2023 --> Jun 2021
- |||||||||| AMG 562 / Amgen
Trial completion date, Trial primary completion date: Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 562 in Subjects With r/r Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma (clinicaltrials.gov) - May 20, 2020
P1, N=85, Recruiting,
Recruiting --> Active, not recruiting | N=85 --> 10 | Trial completion date: Jul 2024 --> Jun 2021 | Trial primary completion date: Jun 2023 --> Jun 2021 Trial completion date: Aug 2023 --> Jul 2024 | Trial primary completion date: Aug 2021 --> Jun 2023
- |||||||||| AMG 562 / Amgen
Trial completion date, Trial primary completion date: Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 562 in Subjects With r/r Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma (clinicaltrials.gov) - Apr 5, 2019
P1, N=85, Recruiting,
Trial completion date: Aug 2023 --> Jul 2024 | Trial primary completion date: Aug 2021 --> Jun 2023 Trial completion date: Dec 2021 --> Aug 2023 | Trial primary completion date: Dec 2021 --> Aug 2021
- |||||||||| AMG 562 / Amgen
Trial completion date, Trial primary completion date: Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 562 in Subjects With r/r Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma (clinicaltrials.gov) - Mar 11, 2019
P1, N=85, Recruiting,
Trial completion date: Dec 2021 --> Aug 2023 | Trial primary completion date: Dec 2021 --> Aug 2021 Trial completion date: May 2021 --> Dec 2021 | Trial primary completion date: May 2021 --> Dec 2021
- |||||||||| AMG 562 / Amgen
Enrollment open, Trial completion date, Trial primary completion date: Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 562 in Subjects With r/r Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma (clinicaltrials.gov) - Nov 14, 2018
P1, N=85, Recruiting,
Trial completion date: May 2021 --> Dec 2021 | Trial primary completion date: May 2021 --> Dec 2021 Not yet recruiting --> Recruiting | Trial completion date: Nov 2020 --> May 2021 | Trial primary completion date: Nov 2020 --> May 2021
- |||||||||| AMG 562 / Amgen
Trial completion date, Trial primary completion date: Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 562 in Subjects With r/r Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma (clinicaltrials.gov) - Sep 11, 2018
P1, N=85, Not yet recruiting,
Not yet recruiting --> Recruiting | Trial completion date: Nov 2020 --> May 2021 | Trial primary completion date: Nov 2020 --> May 2021 Trial completion date: Aug 2020 --> Nov 2020 | Trial primary completion date: Aug 2020 --> Nov 2020
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