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alx148

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Overview

NCI Definition [1]:
A variant of signal regulatory protein alpha (SIRPa) that antagonizes the human cell surface antigen CD47, with potential phagocytosis-inducing, immunostimulating and antineoplastic activities. Upon administration, ALX148 binds to CD47 expressed on tumor cells and prevents the interaction of CD47 with its ligand SIRPa, a protein expressed on phagocytic cells. This prevents CD47/SIRPa-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of phagocytosis. This induces pro-phagocytic signaling mediated by the binding of the pro-phagocytic signal calreticulin (CRT), which is specifically expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related protein (LRP), expressed on macrophages. This results in macrophage activation and the specific phagocytosis of tumor cells. In addition, blocking CD47 signaling activates both an anti-tumor cytotoxic T-lymphocyte (CTL) immune response and T cell-mediated killing of CD47-expressing tumor cells. CD47, also called integrin-associated protein (IAP), is a tumor-associated antigen (TAA) expressed on normal, healthy hematopoietic stem cells (HSC) and overexpressed on the surface of a variety of cancer cells. Expression of CD47, and its interaction with SIRPa, leads to the inhibition of macrophage activation and protects cancer cells from phagocytosis, which allows cancer cells to proliferate.

Clinical Trials

View Clinical Trials for alx148

Alx148 has been investigated in 6 clinical trials, of which 6 are open and 0 are closed. Of the trials investigating alx148, 1 is phase 1 (1 open), 3 are phase 1/phase 2 (3 open), and 2 are phase 2 (2 open).

CBFB-MYH11 Fusion, Complex karyotype, and ERBB2 Amplification are the most frequent biomarker inclusion criteria for alx148 clinical trials.

Head and neck squamous cell carcinoma, acute myeloid leukemia, and adenocarcinoma of the gastroesophageal junction are the most common diseases being investigated in alx148 clinical trials [2].

Top Biomarker Inclusion Criteria for Open Clinical Trials Investigating Alx148
This graph displays the 20 most frequently occurring biomarkers curated on clinical trials investigating alx148 and the cancer types associated with these biomarkers. These numbers are derived from a set of 5,956 clinical trials for which biomarker status defines treatment.

Drug Details

Synonyms [2]:
alx-148, cd47/sirpa-blocking agent alx148, sirpa variant alx148, alx 148, cd47 antagonist alx148, evorpacept
Drug Target(s) [2]:
CD47
NCIT ID [1]:
C132851

References

1. National Cancer Institute. NCI Thesaurus Version 18.11d. https://ncit.nci.nih.gov/ncitbrowser/. [2018-07-30] [2018-08-02].

2. All assertions and clinical trial landscape data are curated from primary sources. You can read more about the curation process here.