GeoVax to Advance Gedeptin® Into First-Line Therapy Neoadjuvant Combination Trial Following Landmark KEYNOTE-689 Results

GeoVax Labs, Inc., a clinical-stage biotechnology company, has announced a strategic shift in its Gedeptin® clinical development program. The new focus is 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 significant improvement in event-free survival (EFS) with the addition of perioperative pembrolizumab in resectable, locally advanced HNSCC patients.

The company's new Phase 2 trial, AdPNP-203, will assess the addition of intra-tumoral Gedeptin®, intravenous fludarabine, and pembrolizumab in patients eligible for curative surgery. The trial aims to evaluate major pathological response (MPR) and associated immunologic and biomarker outcomes following two pre-surgical cycles of therapy, as well as event-free survival over a one-year period. Gedeptin’s tumor-targeting, immune-sensitizing mechanism is expected to enhance immune activation within the tumor microenvironment, potentially overcoming the limitations of checkpoint monotherapy. The trial is slated to begin in 2026.

Dr. Kelly McKee, Chief Medical Officer at GeoVax, emphasized the transformative potential of neoadjuvant checkpoint inhibition in the treatment of head and neck cancer, a view supported by the KEYNOTE-689 results. The integration of Gedeptin into this emerging standard aims to improve local tumor clearance and event-free survival, particularly for high-risk or PD-L1-low patients. David Dodd, Chairman and CEO of GeoVax, highlighted the strategic shift in the program, expressing confidence in Gedeptin’s localized cytotoxic mechanism to improve therapeutic outcomes when combined with systemic checkpoint inhibition for first-line treatment in resectable HNSCC.

The rationale behind this combination strategy is rooted in the observed benefits of neoadjuvant immunotherapy in KEYNOTE-689, despite many patients experiencing local or distant relapse. Gedeptin’s dual cytotoxic and immune-priming mechanism is seen as an ideal complement to checkpoint inhibitors, potentially converting 'cold' tumors into 'hot' immunogenic targets. This approach underscores the need for intensified strategies in the perioperative window to address the limitations of current treatments.

Gedeptin, a gene-directed enzyme prodrug therapy (GDEPT), utilizes a non-replicating adenoviral vector encoding purine nucleoside phosphorylase (PNP) to selectively target tumor cells while sparing healthy tissue. This localized method aims to reduce toxicity, enhance immune visibility, and synergize with immune checkpoint inhibitors. With Orphan Drug Designation for oral and pharyngeal cancers and a robust intellectual property portfolio, GeoVax is at the forefront of developing immune-sensitizing therapies to complement checkpoint inhibitors and overcome tumor immune resistance across solid tumor types.