GeoVax Labs, Inc., a clinical-stage biotechnology company, has announced a significant update to its Gedeptin® clinical development program. The new strategy focuses on evaluating Gedeptin as a neoadjuvant therapy in combination with pembrolizumab for patients with primary, resectable head and neck squamous cell carcinoma (HNSCC). This decision comes in the wake of the landmark KEYNOTE-689 Phase 3 trial results, which showed a notable improvement in event-free survival (EFS) with the addition of perioperative pembrolizumab in resectable, locally advanced HNSCC patients.
The revised Phase 2 trial, named AdPNP-203, aims to assess the efficacy of combining intra-tumoral Gedeptin®, intravenous fludarabine, and pembrolizumab in patients eligible for curative surgery. The trial will focus on major pathological response (MPR) and related immunologic and biomarker outcomes after two pre-surgical therapy cycles, alongside evaluating event-free survival over a year. GeoVax believes that Gedeptin's unique tumor-targeting and immune-sensitizing mechanism could enhance the effectiveness of checkpoint monotherapy by boosting immune activation within the tumor microenvironment. The trial is slated to begin in 2026.
Dr. Kelly McKee, GeoVax's Chief Medical Officer, emphasized the transformative potential of neoadjuvant checkpoint inhibition in treating head and neck cancer, as evidenced by the KEYNOTE-689 results. The integration of Gedeptin into this treatment paradigm aims to improve local tumor clearance and event-free survival, particularly for high-risk or PD-L1-low patients. David Dodd, GeoVax's Chairman and CEO, highlighted the strategic nature of this shift, underscoring the belief that combining Gedeptin's localized cytotoxic mechanism with systemic checkpoint inhibition could significantly enhance therapeutic outcomes for resectable HNSCC patients.
The rationale behind this combination strategy is rooted in the observed benefits of neoadjuvant immunotherapy in the KEYNOTE-689 trial, as noted in a New England Journal of Medicine editorial. Despite these advances, the persistence of local or distant relapse in many patients points to the necessity for more intensive perioperative treatment approaches. Gedeptin's dual mechanism of action—cytotoxic and immune-priming—positions it as an ideal complement to checkpoint inhibitors, potentially transforming 'cold' tumors into 'hot' immunogenic targets.
Gedeptin, a gene-directed enzyme prodrug therapy (GDEPT), utilizes a non-replicating adenoviral vector to deliver purine nucleoside phosphorylase (PNP) directly into tumors. When followed by fludarabine administration, PNP converts the prodrug into a cytotoxic compound, selectively attacking tumor cells while minimizing damage to healthy tissue. This targeted approach aims to reduce toxicity, enhance immune system visibility of the tumor, and synergize with immune checkpoint inhibitors. Gedeptin has been granted Orphan Drug Designation for oral and pharyngeal cancers, supported by a comprehensive intellectual property portfolio.
