Journal for ImmunoTherapy of Cancer (Jun 2024)

Hypothesis: AdAPT-001 and pseudoprogression – when seeing is not necessarily believing

  • Anthony Conley,
  • Christopher Larson,
  • Bryan Oronsky,
  • Meaghan Stirn,
  • Tony R Reid,
  • Scott Caroen

DOI
https://doi.org/10.1136/jitc-2024-008809
Journal volume & issue
Vol. 12, no. 6

Abstract

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The purpose of this commentary is to highlight the high occurrence of clinical pseudoprogression and delayed responses that have been observed to date with the locally injected oncolytic adenovirus, AdAPT-001, currently in a Phase 1/2 clinical trial (NCT04673942) for the treatment of treatment-refractory tumors. Not surprisingly, these have led to confusion about response assessment and whether to continue patients on treatment. AdAPT-001 carries a transforming growth factor (TGF)-beta trap (TGF-β), which sequesters TGF-β, a cytokine that potently regulates inflammation, fibrosis, and immunosuppression in cancer. Pseudoprogression (PsP) or progression prior to response or stabilization, has been widely recognized with radiotherapy for primary brain tumors and immune checkpoint inhibitors (ICIs). PsP has also been described and documented in the context of oncolytic virotherapy but perhaps to a lesser extent. However, repeated intratumoral injections with these immunostimulatory agents may induce a more intense immune response and release more antigenic epitopes than with ICIs, for example, which are strictly T-cell directed rather than also tumor-directed like AdAPT-001.