zimberelimab

Overview

Zimberelimab (AB122) is a fully humanized IgG4 monoclonal antibody that blocks the interaction between programmed cell death protein 1 (PD-1, encoded by PDCD1) and its ligands PD-L1 (CD274) and PD-L2. By relieving PD-1-mediated inhibition of cytotoxic T lymphocytes, zimberelimab aims to restore anti-tumor immune surveillance. In the ROBIN ImmunoRad rectal cancer program, it is being tested in combination with the adenosine-receptor antagonist etrumadenant and FOLFOX chemotherapy in the context of short-course radiotherapy (SCRT), on the rationale that RT-induced immunogenic cell death creates a neoantigen-rich, inflamed microenvironment that PD-1 blockade can capitalize on — while concurrent adenosine-axis blockade removes a parallel immunosuppressive mechanism.

Evidence in the corpus

  • The ROBIN ImmunoRad MCT2 trial (NCT05024097, Phase I/II) at Weill Cornell and 9 co-enrolling international centers is evaluating SCRT + etrumadenant + zimberelimab + FOLFOX in locally advanced rectal cancer. As of the white paper, 21 patients were enrolled. Preliminary CR rates were 1/5 (20%) in Part I and 11/15 patients (82%) in Part II stage 1, though these are early-accrual results and formal efficacy conclusions are pending. PMID:41941260
  • The paper positions zimberelimab as the PD-1-blockade component of the ImmunoRad combination strategy, complementing etrumadenant (adenosine axis) and FOLFOX (cytotoxic backbone) in an RT-primed microenvironment. Spatial transcriptomics (Visium HD) on MCT1 biopsies is being used to characterize the RT-associated lymphocyte redistribution and macrophage signaling that provides the biological rationale for adding checkpoint blockade. 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.