Drug intelligence / Profile preview

avelumab + M9241

Development stage
Unknown
Lead developer
Merck
Modality
Immunomodulatory ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
Administration
Intravenous, Subcutaneous
01

Overview

Avelumab + M9241 is a combination investigational therapy comprising an anti–PD-L1 monoclonal antibody (avelumab) and a novel immunocytokine (M9241, also known as NHS-IL12), which contains interleukin-12 heterodimers fused to a tumor-targeting antibody. Avelumab blocks the immune checkpoint protein PD-L1, reactivating T cells to mount an immune response against tumor cells, while M9241 delivers IL-12 to the tumor microenvironment to stimulate interferon gamma (IFN-γ) production and enhance T-cell and NK-cell–mediated cytotoxicity. Preclinical models indicated additive or synergistic antitumor activity. The combination has been evaluated in a first-in-human phase Ib clinical trial (JAVELIN IL-12) in patients with locally advanced or metastatic solid tumors, and in a dose-expansion phase in urothelial carcinoma. While the regimen was generally well tolerated, the expansion phase did not meet efficacy criteria for further advancement in urothelial carcinoma[1][2][3][4].

Other names
NH12-IL12 + avelumabM9241 (NHS-IL12) + avelumab
02

Targets

IL-12R (Interleukin-12 receptor)CD274 (Programmed cell death protein 1 ligand 1)Nucleosome (DNA–histone complex)

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