Gentulizumab in Relapsed/Refractory Acute Myelogenous Leukemia or Myelodysplastic Syndrome
Status:
Recruiting
Trial end date:
2024-07-30
Target enrollment:
Participant gender:
Summary
Gentulizumab Injection is an anti-CD47 monoclonal antibody. As a member of the immunoglobulin
superfamily, CD47 is expressed at low levels on many cells of the body, including
hematopoietic cells (red blood cells, lymphocytes, platelets, etc.) and non-hematopoietic
cells (placenta, liver and brain cells). It is overexpressed on many types of tumors. There
is abundant supportive evidence that the expression of CD47 on tumor cells, though binding to
SIRP on professional phagocytes, acts to prevent tumor cell phagocytosis, inhibit antigen
cross-presentation, and block the production of pro-inflammatory molecules, thus promoting
the development of a "cold" tumor microenvironment. Blocking CD47 can not only stimulate
phagocytosis to cancer cells, but also promote macrophage recruitment towards neoplasm. At
the same time, blocking CD47 can stimulate macrophages to secrete cytokines. These cytokines
and chemokines can further recruit other immune cells to neoplasms. These newly recruited
immune cells can provide a positive feedback and enhance the therapeutic response of blocking
CD47. Therefore, the CD47/SIRPĪ± axis blocking appears to be a potential therapeutic target
for neoplasm.
Currently, no anti-CD47 antibody product has been granted marketing authorization for
progressive hematological malignancies. Whereas Hu5F9-G4, a CD47 monoclonal antibody, is
being tested in a series of ongoing clinical trials for AML, MDS, lymphomas and multiple
solid tumors. The clinical research was designed based on non-clinical data and relevant
experience of other CD47 monoclonal antibody.
In this phase Ia study, "3 + 3" dose escalation method combined with rapid titration will be
used to evaluate the dose limiting (DLT) toxicity of each dose group, evaluate the safety and
tolerance of Gentulizumab in the treatment of patients with progressive hematological
malignancies, and determine the maximum tolerated dose (MTD) and phase II recommended dose
(RP2D); At the same time, the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity,
preliminary efficacy and biomarkers of gentulizumab will be evaluated to provide sufficient
basis for new drug application (NDA) guidance and further clinical use.
Phase:
Phase 1
Details
Lead Sponsor:
GeneScience Pharmaceuticals Co., Ltd.
Collaborators:
First Affiliated Hospital of Zhejiang University Ruijin Hospital Shanghai Tong Ren Hospital