etrumadenant

Overview

Etrumadenant (AB928) is a small-molecule dual antagonist of the adenosine A2A receptor (ADORA2A) and A2B receptor (ADORA2B). Extracellular adenosine accumulates in the tumor microenvironment (TME) — particularly following radiation-induced cell death and ATP release — and suppresses anti-tumor immunity by activating A2A/A2B receptors on T cells, NK cells, and dendritic cells. By blocking adenosine signaling, etrumadenant aims to relieve immunosuppression in irradiated tumors and potentiate the adaptive immune response triggered by RT. Its combination with PD-1 blockade (zimberelimab) and chemotherapy (FOLFOX) in the context of short-course radiotherapy (SCRT) is being evaluated on the premise that RT-induced immunogenic cell death, adenosine-pathway blockade, and checkpoint inhibition may synergize to enhance pathological complete response (pCR) rates in rectal cancer.

Evidence in the corpus

  • The ROBIN ImmunoRad center (Weill Cornell + 9 collaborating institutions) is running MCT2 (NCT05024097), a Phase I/II trial of SCRT + etrumadenant + zimberelimab + FOLFOX in locally advanced rectal cancer. As of the white paper, 21 patients had been enrolled. Preliminary results showed a complete response (CR) rate of 1/5 (20%) in Part I and 11/15 stage-1 patients in Part II (82% CR), though sample sizes are small and accrual was ongoing. PMID:41941260
  • The paper frames etrumadenant’s role in MCT2 as targeting the adenosine immunosuppressive axis that RT is expected to activate in the TME, complementing PD-1 blockade by zimberelimab and systemic cytotoxicity from FOLFOX. PMID:41941260

Resistance mechanisms

No resistance mechanisms reported in the corpus at this time.

Cancer types (linked)

  • READ — rectal adenocarcinoma; ImmunoRad MCT2 (NCT05024097).

Sources

  • PMID:41941260 — Gregucci et al. 2026, Clin Cancer Res. ROBIN white paper; ImmunoRad MCT2 (NCT05024097) preliminary CR data with SCRT + etrumadenant + zimberelimab + FOLFOX in rectal cancer.

This page was processed by crosslinker on 2026-05-04.

This page was processed by crosslinker on 2026-05-04.