avelumab

Overview

Avelumab is a fully human IgG1 monoclonal antibody that targets PD-L1 (CD274), blocking its interactions with both PD-1 (PDCD1) and B7-1 (CD80). Unlike IgG4-based anti-PD-1/PD-L1 antibodies, avelumab retains Fc-mediated antibody-dependent cellular cytotoxicity (ADCC), which may contribute additional tumor-cell killing. In the radiation-oncology context, avelumab has been evaluated as an addition to cisplatin-based chemoradiation (CRT) in head and neck squamous cell carcinoma (HNSCC), on the premise that RT-induced PD-L1 upregulation and immunogenic cell death create a favorable microenvironment for checkpoint blockade.

Evidence in the corpus

  • The ROBIN GenRad center analyzed an expansion cohort from the Javelin HN100 trial — a Phase III study of chemoradiation ± avelumab in locally advanced HNSCC. A notable finding from this analysis was that intratumoral bacteria represent a major source of resistance to therapy in HNSCC, suggesting the tumor microbiome may undermine CRT-immunotherapy combinations. These results were reported as preliminary within the ROBIN white paper; formal primary publication of the Javelin HN100 expansion analysis was not cited. PMID:41941260
  • In the GenRad HNSCC context, avelumab is discussed alongside PD-1-blocking re-irradiation approaches (NCT03521570) as part of a broader portfolio of radioimmunotherapy strategies in HNSCC. PMID:41941260
  • Avelumab+axitinib (JAVELIN Renal 101) demonstrated significant PFS benefit for ICI/ICI-combo-preferred ccRCC patients (p=0.000007) in the HiTME decision-tree analysis; the ICI responder model achieved ROC-AUC=0.78 on JAVELIN validation PMID:22138691
  • Cited as an investigational anti-PD-L1 agent in the NPC therapeutic landscape review PMID:24952746

Resistance mechanisms

  • Intratumoral bacteria in HNSCC identified as a major source of resistance to CRT (cisplatin backbone) ± avelumab in the Javelin HN100 expansion cohort analysis (GenRad/ROBIN). PMID:41941260

Cancer types (linked)

  • HNSC — head and neck squamous cell carcinoma; Javelin HN100 expansion cohort (GenRad).

Sources

  • PMID:41941260 — Gregucci et al. 2026, Clin Cancer Res. ROBIN white paper; GenRad analysis of Javelin HN100 CRT ± avelumab expansion cohort; intratumoral bacteria identified as resistance mechanism.

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This page was processed by crosslinker on 2026-05-04. - PMID:22138691

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