AMG 562 / Amgen - LARVOL DELTA

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) - P1 | N=10 | Terminated | Sponsor: Amgen | Completed ➔ Terminated; Amgen decided to discontinue study because of a business decision and not because of safety reasons

Trial termination • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • MYC

T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals. (PubMed, Blood) - "In relapsed/refractory B-cell precursor acute lymphoblastic leukemia patients, 28-day continuous infusion with the CD19xCD3 bispecific molecule blinatumomab led to declining T-cell function. 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."

Journal • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

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) - P1 | N=10 | Completed | Sponsor: Amgen | Active, not recruiting ➔ Completed

Trial completion • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CD19 • MYC

Treatment-Free Intervals during CD19xCD3 BiTE® Construct-Mediated T-Cell Stimulation Induce Functional Reinvigoration and Transcriptional Reprogramming of Exhausted T Cells (ASH 2021) - "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."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • BTLA • CCNB1 • CD19 • CD2 • CD8 • CDK1 • GZMB • IL2RA • IL7R • IRF4 • LAG3 • NFATC1 • NR4A3 • PD-1 • PLK1 • SLC3A2 • TRAF1

"#ASH21 #leusm Zieger: treatment free intervals when using AMG 562 (t1/2 extended Blinatumomab) recruits and functionally reinvigorates exhausted anti-leukemic T cells." (@hemedoc)

Hematological Malignancies • Leukemia

Reduction of CD19-BiTE® construct-induced T-cell exhaustion through breaks in treatment (DGHO 2021) - "To simulate continuous BiTE® construct infusion in vitro, healthy donor T cells were stimulated for 28 days with the CD19 half-life extended BiTE® construct AMG 562 in the presence of CD19 + OCI-Ly1 cells. 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."

IO biomarker • Infectious Disease • CD19 • CDK1 • GZMB • IFNG • IL7R • NR4A3 • PD-1

[VIRTUAL] PHASE I STUDY OF THE CD19/CD3 HALF-LIFE EXTENDED BITE® MOLECULE AMG 562 IN RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA, MANTLE CELL LYMPHOMA AND FOLLICULAR LYMPHOMA (ICML 2021) - P1 | "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 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • FDG PET

[VIRTUAL] Treatment-Free Intervals Mitigate T-Cell Exhaustion Induced By Continuous CD19xCD3-BiTE® Construct Stimulation in Vitro (ASH 2020) - "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."

Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • CD19 • CD8 • GZMB • IFNG • IL2 • TNFA

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) - P1; N=10; Active, not recruiting; Sponsor: Amgen; Trial completion date: Jun 2021 ➔ Mar 2022; Trial primary completion date: Jun 2021 ➔ Mar 2022

Clinical • Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

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) - P1; N=10; Active, not recruiting; Sponsor: Amgen; Recruiting ➔ Active, not recruiting; N=85 ➔ 10; Trial completion date: Jul 2024 ➔ Jun 2021; Trial primary completion date: Jun 2023 ➔ Jun 2021

Clinical • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • CD19 • MYC

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) - P1; N=85; Recruiting; Sponsor: Amgen; Trial completion date: Aug 2023 ➔ Jul 2024; Trial primary completion date: Aug 2021 ➔ Jun 2023

Clinical • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A FIRST‐IN‐HUMAN STUDY OF A HALF‐LIFE EXTENDED CD19‐TARGETING BiTE IN RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA, MANTLE CELL LYMPHOMA OR FOLLICULAR LYMPHOMA (ICML 2019) - "Adults with relapsed/refractory (R/R) DLBCL treated with blinatumomab, a canonical BiTE® immunotherapy also targeting CD19, have shown durable complete responses. This study will identify initial safety, PK, and efficacy profile of the HLE BiTE® AMG 562 in adults with R/R DLBCL, MCL, and FL."

P1 data

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) - P1; N=85; Recruiting; Sponsor: Amgen; Trial completion date: Dec 2021 ➔ Aug 2023; Trial primary completion date: Dec 2021 ➔ Aug 2021

Clinical • 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) - P1; N=85; Recruiting; Sponsor: Amgen; Trial completion date: May 2021 ➔ Dec 2021; Trial primary completion date: May 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date