Results from a Phase II trial investigating pembrolizumab in combination with PRGN-2009 for newly diagnosed HPV-associated oropharyngeal cancer were posted on 2026-06-23. The study reported that 93.8% of participants experienced a 2-fold increase in CD3+ tumor-infiltrating T cells post-treatment. Crucially, the trial recorded zero treatment-related serious adverse events across all grades.
Background
Pembrolizumab (Keytruda) is an established immunotherapy. PRGN-2009 is an immunotherapeutic HPV vaccine. The combination was investigated for newly diagnosed HPV-associated oropharyngeal cancer, a condition noted as common, where both drugs have individually shown efficacy.
Trial design
This was a Phase II trial (NCT05996523) enrolling 26 adult participants aged 18 and older. The study focused on individuals newly diagnosed with HPV-positive Oropharyngeal Squamous Cell Carcinoma (SCC). Participants received PRGN-2009 (5x10^11 viral particles subcutaneously) combined with pembrolizumab (200mg intravenous).
Key results
The trial reported several key measurements:
- A significant increase in tumor-infiltrating T cells: 93.8% of participants in the PRGN-2009 plus pembrolizumab arm showed a 2-fold increase of Cluster of Differentiation 3 (CD3+) tumor-infiltrating T cells in post-treatment biopsies compared to pre-treatment.
- Safety profile: No treatment-related serious adverse events were reported across all grades. Specifically, 0 serious adverse events were recorded for Grade 1, Grade 2, Grade 3, Grade 4, and Grade 5.
- Overall adverse events: A total of 21 participants experienced serious and/or non-serious adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) in the PRGN-2009 plus pembrolizumab arm.
- Comparison to prior study: In a comparison to participants receiving PRGN-2009 in study NCT04432597, the current trial's PRGN-2009 plus pembrolizumab arm showed a 2-fold increase in CD3+ tumor-infiltrating lymphocytes (TILs) in 93.8% of participants, while the comparison group showed 12.5%.
What this means
The results suggest that the combination of pembrolizumab and PRGN-2009 may be effective in stimulating an immune response in patients with newly diagnosed HPV-associated oropharyngeal cancer, as evidenced by the high percentage of participants showing increased CD3+ tumor-infiltrating T cells. The favorable safety profile, with zero reported treatment-related serious adverse events, is also a notable finding. The comparison showing a significantly higher percentage of T-cell increase in the combination arm versus PRGN-2009 alone hints at a synergistic effect, warranting further investigation into this therapeutic strategy for HPV-positive cancers.
Source
The trial results were posted on 2026-06-23 on ClinicalTrials.gov, an official database of clinical studies. The full details are available on clinicaltrials.gov under the identifier NCT05996523.