Drug intelligence / Profile preview

maplirpacept + isatuximab + carfilzomib + dexamethasone

Development stage
Discontinued
Lead developer
Pfizer
Modality
Fc-Fusion Proteins → Carrier/Scaffold Proteins → Recombinant Proteins and Enzymes, Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous, Oral
01

Overview

This regimen is an **experimental quadruple combination therapy** comprised of maplirpacept, isatuximab, carfilzomib, and dexamethasone. Each agent has a distinct mechanism: - **Maplirpacept** is a recombinant fusion protein that acts as a decoy receptor to block CD47, an immune checkpoint, thereby promoting phagocytosis of tumor cells (innate immune checkpoint inhibition, "don't eat me" signal blocking). - **Isatuximab** is a monoclonal antibody targeting CD38, inducing direct cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), and phagocytosis of myeloma cells. - **Carfilzomib** is a next-generation irreversible proteasome inhibitor, resulting in accumulation of misfolded proteins and apoptosis in cancer cells. - **Dexamethasone** is a synthetic glucocorticoid that promotes apoptosis in lymphoid cells and exerts immunosuppressive, anti-inflammatory activities. The combination is under clinical investigation primarily for **multiple myeloma**, aiming to exploit synergistic mechanisms of immune modulation and targeted cytotoxicity for enhanced anti-myeloma effect.

02

Targets

CD38 (Cluster of Differentiation 38)GR (Glucocorticoid receptor)PSMB5 (Proteasome subunit beta Type-5)CD47 (Cluster of Differentiation 47)

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