BETA PRIME: Phase I study of AdAPT-001 as monotherapy and combined with a checkpoint inhibitor in superficially...

Area of Science:

• Oncolytic virotherapy
• Immunotherapy
• Gene therapy

Background:

• Transforming growth factor beta (TGF-β) is a profibrotic and immunosuppressive cytokine implicated in tumor progression.
• AdAPT-001 is a novel oncolytic adenovirus engineered to neutralize TGF-β isoforms 1 and 3.
• Preclinical studies demonstrated AdAPT-001's ability to eliminate tumors and elicit systemic anti-tumor immunity.

Purpose of the Study:

• To evaluate the safety and tolerability of AdAPT-001 in a first-in-human Phase I clinical trial.
• To determine the recommended Phase II dose for AdAPT-001, administered alone and in combination with a checkpoint inhibitor.
• To assess the preliminary efficacy of AdAPT-001 in patients with treatment-refractory solid tumors.

Main Methods:

• Phase I, dose-escalation and dose-expansion study design.
• Adult patients with treatment-refractory superficially accessible solid tumors enrolled.
• AdAPT-001 administered intravenously alone or combined with a checkpoint inhibitor.

Main Results:

• Preclinical data showed AdAPT-001 eradicated both treated and distant tumors.
• AdAPT-001 induced systemic CD8+ T cell-mediated antitumor immunity, providing protection against tumor rechallenge.
• AdAPT-001 sensitized resistant tumors, enhancing efficacy when combined with checkpoint blockade.

Conclusions:

• AdAPT-001 demonstrates promising preclinical anti-tumor activity and immunomodulatory effects.
• The Phase I study will establish the safety profile and optimal dosing of AdAPT-001.
• AdAPT-001 holds potential as a novel therapeutic agent for solid tumors, particularly in combination strategies.