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Area of Science:

  • Oncology
  • Immunotherapy
  • Virology

Background:

  • Oncolytic virotherapy is an emerging cancer treatment strategy.
  • AdAPT-001 is a locally injected oncolytic adenovirus designed to treat refractory tumors.
  • AdAPT-001 incorporates a transforming growth factor-beta (TGF-β) trap to modulate the tumor microenvironment.

Purpose of the Study:

  • To highlight the frequent occurrence of clinical pseudoprogression (PsP) and delayed responses with AdAPT-001.
  • To discuss the implications of these observations for response assessment and treatment continuation.
  • To provide context for PsP in oncolytic virotherapy compared to other cancer treatments.

Main Methods:

  • The commentary reviews clinical observations from a Phase 1/2 trial of AdAPT-001 (NCT04673942).
  • It discusses the mechanism of action of AdAPT-001, including its TGF-β trap.
  • It compares the observed phenomena with known responses to radiotherapy and immune checkpoint inhibitors (ICIs).

Main Results:

  • High rates of pseudoprogression and delayed responses have been observed with AdAPT-001.
  • These responses can cause confusion in evaluating treatment efficacy and patient management.
  • Intratumoral injection of immunostimulatory agents like AdAPT-001 may elicit a stronger immune response than ICIs.

Conclusions:

  • Pseudoprogression and delayed responses are significant considerations for AdAPT-001 therapy.
  • Careful interpretation of response assessment is crucial for patients receiving AdAPT-001.
  • Further research is needed to optimize the use of AdAPT-001 and manage treatment-related complexities.