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

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.