A Multicenter, Open-label, Dose-escalating, Phase I Trial With GEM333, a CD33 Targeted Bispecific Antibody Engaging T-cells, in Relapsed or Refractory Acute Myeloid Leukemia

This dose-escalating phase I trial assesses for the first time the safety, the side effects and the harmlessness, as well as the therapeutical benefit of the new study drug GEM333 in patients with acute myeloid leukemia (AML). This AML was relapsed after previous therapy or was refractory to the standard therapy.

Start Date11 Apr 2018

Sponsor / Collaborator

AvenCell Europe GmbHStartup

[+1]

100 Clinical Results associated with GEM-333

100 Translational Medicine associated with GEM-333

100 Patents (Medical) associated with GEM-333

Literatures (Medical) associated with GEM-333

18 Apr 2024·Blood

Consensus recommendations on the management of toxicity associated with CD3×CD20 bispecific antibody therapy

Article

Author: McKenna, Marshall ; Lunning, Matthew ; Shah, Nirav N. ; Abramson, Jeremy S. ; Ayed, Ayed ; Hutchings, Martin ; Weiss, Jonathan ; Osterson, Jane ; Caimi, Paolo ; Ursu, Renata ; Armand, Philippe ; Sharman, Jeffrey ; Bartlett, Nancy ; Crombie, Jennifer L. ; Thieblemont, Catherine ; Graff, Tara ; Nastoupil, Loretta ; Kahl, Brad ; Zelenetz, Andrew ; Kamdar, Manali ; Bannerji, Rajat ; Flinn, Ian ; Patel, Krish ; Parsons, Benjamin ; Brody, Joshua ; Herrera, Alex ; Dickinson, Michael ; Falchi, Lorenzo ; Budde, Lihua Elizabeth ; Karimi, Yasmin H. ; Nachar, Victoria ; Phillips, Tycel ; Smith, Sonali

AbstractBispecific antibodies (BsAb) that target CD3 and CD20 represent a new milestone in the treatment of patients with B-cell non-Hodgkin lymphoma. These drugs have demonstrated remarkable single-agent activity in patients with heavily pretreated disease, and 3 drugs have so far received regulatory approvals in various countries. However, BsAbs can potentially lead to severe toxicity associated with T-cell activation, particularly cytokine release syndrome (CRS). The anticipated widespread use of these off-the-shelf products poses challenges for implementation and highlights the need for guidance in anticipating, mitigating, and managing adverse events. In clinical trials, guidance for the evaluation and treatment of CRS and neurotoxicity associated with BsAb therapy has been modeled after algorithms originally created for chimeric antigen receptor (CAR) T-cell therapies and other immune effector therapies, yet notable differences in timing, quality, and severity exist between the toxicities of BsAbs and CAR T-cell therapies. We therefore convened an international panel of academic and community practice physicians, advanced practitioners, registered nurses, and pharmacists with experience using CD3×CD20 BsAbs in clinical trial and off-trial settings to provide comprehensive, consensus-based recommendations specific to the assessment and management of CD3×CD20 BsAb–related toxicities.

01 Dec 2019·Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

Characterization of a Novel Bispecific Antibody That Activates T CellsIn Vitroand Slows Tumor GrowthIn Vivo

Article

Author: Chiu, Mark L. ; Brosnan, Kerry ; Chornoguz, Olesya ; Emmell, Eva ; Leettola, Catherine N. ; Santulli-Marotto, Sandra ; Leander, Karen

Although CD3 T cell redirecting antibodies have been successfully utilized for the treatment of hematological malignancies (blinatumomab), the T cell signaling pathways induced by these molecules are incompletely understood. To gain insight into the mechanism of action for T cell redirection antibodies, we created a novel murine CD3xEpCAM bispecific antibody that incorporates a silent Fc to dissect function and signaling of murine CD8 OT1 T cells upon stimulation. T cell-mediated cytotoxicity, cytokine secretion, expression of activation markers, and proliferation were directly induced in T cells treated with the novel CD3xEpCAM bispecific molecule in vitro in the presence of epithelial cell adhesion molecule (EpCAM) expressing tumor cells. Nanostring analysis showed that CD3xEpCAM induced a gene expression profile that resembled antigen-mediated activation, although the magnitude was lower than that of the antigen-induced response. In addition, this CD3xEpCAM bispecific antibody exhibited in vivo efficacy. This is the first study that investigates both in vitro and in vivo murine CD8 T cell function and signaling induced by a CD3xEpCAM antibody having a silent Fc to delineate differences between antigen-independent and antigen-specific T cell activation. These findings expand the understanding of T cell function and signaling induced by CD3 redirection bispecific antibodies and may help to develop more efficacious CD3 redirection therapeutics for cancer treatment, particularly for solid tumors.

15 Jan 2019·Clinical Cancer ResearchQ1 · MEDICINE

FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease

Q1 · MEDICINE

Article

Author: Xu, Qing ; Farrell, Ann T. ; Deisseroth, Albert ; Jen, Emily Y. ; Shen, Yuan Li ; Schetter, Aaron ; Philip, Reena ; Przepiorka, Donna ; Roscoe, Donna ; Pazdur, Richard ; Sridhara, Rajeshwari

AbstractOn March 29, 2018, the FDA granted accelerated approval for blinatumomab (Blincyto; Amgen, Inc.) for the treatment of adults and children with B-cell precursor acute lymphoblastic leukemia (BCP ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%. Blinatumomab is a CD3xCD19 bispecific antibody approved previously for the treatment of relapsed or refractory BCP ALL. The basis for this accelerated approval was a single-arm trial. For the 86 patients in first and second complete remission with MRD ≥ 0.1%, conversion to MRD < 0.01% was achieved after one cycle of blinatumomab by 85.2% [95% confidence interval (CI): 73.8%, 93.0%] and 72.0% (95% CI: 50.6%, 87.9%), respectively, and the estimated median hematologic relapse-free survivals (RFS) were 35.2 months (95% CI: 0.4–53.5) and 12.3 months (95% CI: 0.7–42.3), respectively. Hematologic RFS was considered substantial independent of whether patients underwent subsequent allogeneic stem cell transplantation. The safety profile for blinatumomab was established in prior studies, and no new safety signals were observed in the new population. Cytokine release syndrome and neurotoxicity remain significant risks. The FDA is requiring confirmation of clinical benefit in a randomized trial.

100 Deals associated with GEM-333

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia	Preclinical	DE	GEMoaB Monoclonals GmbH	11 Apr 2018
Refractory acute myeloid leukemia	Preclinical	DE	AvenCell Europe GmbHStartup	11 Apr 2018
Relapsing acute myeloid leukemia	Preclinical	DE	AvenCell Europe GmbHStartup	11 Apr 2018

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