GeoVax Labs published peer-reviewed results from a Phase 1/2 trial showing that repeated intratumoral dosing of Ad/PNP (Gedeptin) followed by systemic fludarabine was well tolerated in patients with recurrent head and neck cancer and supports further development in earlier disease and combination settings.
ATLANTA — The manuscript, published in JCO Oncology Advances, reports findings from a multicenter study that enrolled heavily pretreated patients with recurrent head and neck cancer who had received a median of four prior lines of systemic therapy. Patients received intratumoral Gedeptin injections followed by intravenous fludarabine on a 28-day schedule.
The therapy demonstrated an acceptable safety profile with no new safety signals. Serious adverse events were uncommon and generally deemed unrelated to treatment, and no deaths were attributed to the study therapy.
Clinical activity was limited but notable given the refractory population: three of eight evaluable patients (37.5%) achieved stable disease. Tumor biopsies confirmed uptake and expression of the E. coli purine nucleoside phosphorylase (PNP) transgene in all evaluable patients, supporting the mechanism of the gene-directed enzyme prodrug therapy.
The authors note that earlier intervention, higher vector dosing, improved tumor transduction or combination approaches—particularly with immune checkpoint inhibitors—may increase efficacy. Preclinical data cited in the manuscript indicate that Gedeptin-mediated tumor destruction can sensitize tumors to checkpoint blockade.
J. Marc Pipas, GeoVax’s executive medical director for oncology, said the results reinforce the scientific rationale for the platform, highlighting safety with repeated intratumoral dosing and confirmation of robust tumor transduction. Kelly T. McKee, the company’s chief medical officer, said the findings support further evaluation in patients with lower tumor burden, less prior treatment, and in combination with checkpoint inhibitors. David Dodd, chairman and CEO, said the publication underscores the need for new approaches to treat recurrent head and neck cancers and signaled plans to expand development into earlier disease settings and combination regimens.
Gedeptin is a non-replicating adenoviral vector that delivers the E. coli PNP gene into tumor tissue. After intratumoral injection, systemic fludarabine is converted by PNP-expressing tumor cells into the cytotoxic metabolite 2-fluoroadenine (F-Ade). The platform is described as tumor-agnostic, with a strong bystander effect that can kill neighboring cancer cells despite limited direct transduction, and as having immune-sensitizing properties that may enhance responses to checkpoint inhibitors.
GeoVax said Gedeptin is progressing toward combination therapy evaluations in neoadjuvant clinical programs, with plans to assess combinations with agents such as pembrolizumab to strengthen antitumor immune activation.
About GeoVax: GeoVax Labs, Inc. is a clinical-stage biotechnology company developing vaccines for infectious diseases and immunotherapies for solid tumors. Its lead programs include a next-generation COVID-19 vaccine in Phase 2 trials and the Gedeptin oncolytic gene-directed therapy recently evaluated in a multicenter Phase 1/2 trial for advanced head and neck cancers. The company is also developing a vaccine targeting Mpox and smallpox.
For more information, visit www.geovax.com.
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