There are currently no HPV-specific FDA-approved immunotherapies to treat HPV-related cancers. The IMMUNOCERV study conducted by investigators at MD Anderson was designed to test the hypothesis that Versamune, a novel HPV-specific vaccine, would be safe and effective in combination with standard-of-care chemoradiation for locally advanced HPV-related cervical cancer.
Dr. Ann Klopp, a Professor of Radiation Oncology at The University of Texas MD Anderson Cancer Center, answered some questions about the study for Breaking Cancer News.
Can you very briefly explain the importance of this stage of cervical cancer?
Locally advanced cervical cancer represents a median proportion of 37% among all cervical carcinomas. Although most early-stage patients have a good prognosis with surgery, patients with locally advanced disease suffer a worse prognosis and are in need of new approaches to improve their outcomes.
Can you please provide a brief description of Versamune and how it works?
Versamune® is a T-cell activating platform engineered and developed to successfully recruit, train and arm T-cells to execute a precise attack. Versamune® has been shown to induce a significantly higher quantity and quality of highly potent (polyfunctional) killer T-cells, a specific sub-type of killer T-cell that is more powerful at attacking cancer.
By promoting the induction of the right type of killer T-cell targeting tumors, with strong potency and in the right quantity, Versamune® has demonstrated impressive efficacy in trials to date.
Can you give us a basic biochemical description of how Versamune works and how it’s administered?
Versamune® HPV (formerly PDS0101)—which was used in this study in combination with standard-of-care chemoradiation for locally advanced HPV-related cervical cancer (NCT04580771)—is an HPV-specific vaccine containing peptide pools encoding E6/E7 antigens. There are currently no HPV-specific FDA-approved immunotherapies to treat HPV-related cancers.
One of the biggest challenges in developing a potent immunotherapy has been uptake by dendritic cells, which are the primary cells responsible for directing the immune system. Versamune® HPV is administered subcutaneously (i.e. injected directly into the fatty tissue layer of the skin) and is designed specifically to be taken up by dendritic cells in the skin. Versamune® HPV nanoparticles are sized to mimic viruses that are normally taken up as part of the natural function of the dendritic cells, facilitating efficient uptake of the Versamune® based immunotherapy.
Studies evaluating the uptake of Versamune® HPV nanoparticles by dendritic cells and epithelial cells, found almost exclusive uptake by the dendritic cells. Four hours following a single subcutaneous injection, about 80% of the dendritic cells in the draining lymph node were found to have taken up the Versamune® HPV-based immunotherapy.
If these future trials are successful, how much could this new treatment move the ball forward for cervical cancer patients?
Although our local therapies are fairly good at eliminating the bulk of tumor cells, patients with locally advanced cervical cancer frequently develop disease recurrence leading to 5-year disease-free and overall survival rates around 70%. Our hope is that adding the tumor-targeted immune therapy, Versamune® HPV will train patients’ immune systems to fight their cancer and prevent it from coming back.
What have been the biggest obstacles getting in the way of moving treatments forward in this indication?
The major challenges we think about are the time it takes to conduct clinical trials and the cost of clinical trials large enough to secure regulatory approvals. However, the IMMUNOCERV study is promising and warrants further investigation in a larger trial.
Can you tell us more about the IMMUNOSERV study design?
- The IMMUNOCERV trial was designed to test whether Versamune® HPV would be safe and effective for these patients with locally advanced HPV-related cervical cancer in combination with standard-of-care chemoradiation.
- The single-arm, Phase 2 study (NCT04580771) enrolled adult patients with newly diagnosed, biopsy-proven locally advanced (at least 5 cm in size) squamous cell carcinoma of the cervix. These patients received up to five doses of Versamune® HPV alongside chemoradiation.
The primary endpoint for this study was the rate of clinically significant acute toxicities. Secondary endpoints included the rate of complete metabolic response and gross tumor volume reduction, progression-free survival and overall survival at 12 and 18 months after completion of chemoradiation.
What were the results for the study?
- The latest data from this study was presented at the American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting. Highlights from the presentation include:
- All patients received at least 2 doses of Versamune® HPV.
- Median follow-up was 19 months.
- 36-month overall survival rate was 84.4%, and 100% for the eight patients who received all five doses of Versamune® HPV. Historical published data show 36-month OS rate with chemoradiation in this population of approximately 64%.2
- 36-month progression free survival rate was 74.9%, among all patients and 100% for the eight patients who received all five doses of Versamune® HPV. Historical published data show 36-month PFS rate with chemoradiation in this population of approximately 61%.2
- Complete metabolic response was achieved in 15/17 (88%) patients.
- Versamune® HPV appeared to be safe and well-tolerated. The most common treatment-related toxicities were injection site reactions in twelve patients (71%).
