PDS Biotechnology Corporation (Nasdaq: PDSB) is set to initiate its VERSATILE-003 Phase 3 clinical trial in the first quarter of 2025. This trial will evaluate the efficacy of Versamune® HPV in combination with pembrolizumab for the first-line treatment of recurrent and/or metastatic (R/M) HPV16-positive head and neck squamous cell carcinoma (HNSCC). The company has received Fast Track designation from the FDA for the combination therapy in R/M HNSCC. The trial aims to address the growing need for targeted therapies in the HPV16-positive HNSCC subgroup, which is becoming increasingly prevalent in the US and EU. The study design incorporates key feedback from oncologists and regulatory bodies to optimize patient outcomes and accelerate potential approval. The VERSATILE-003 trial is registered on ClinicalTrials.gov with the identifier NCT06790966.
Trial Design and Modifications
The updated VERSATILE-003 trial design will include approximately 350 patients. The trial retains statistical power, maintains a 2 to 1 randomization, and remains within the confines of discussions with the FDA on a registrational trial design. Median overall survival remains as the primary endpoint. The FDA clearance decision is expected by mid-December.
VERSATILE-002 Study Data
The updated design is informed by the observed durability of the clinical responses in the VERSATILE-002 study seen over the last year, with the most recent data presented at the ESMO Congress in September. The data demonstrated the following:
- Median overall survival has remained at 30 months over the last two data cuts and the lower limit of the 95% confidence interval improved to approximately 20 months. The best published median overall survival for pembrolizumab is approximately 18 months.
- Objective response rate improved from 26% to 36%. Published objective response rate for pembrolizumab is 19% to 25%.
- Disease control rate improved from 70% to 77%.
- The number of patients with complete or near complete responses of 90% to 100% tumor shrinkage increased from 6% to 21%.
- 9% of patients had a complete response versus 3% a year earlier.
- Treatment related adverse events or TRAEs of grade 3 or higher were seen in 9 out of 87 patients, with 1 out of 87 patients having a grade 4 TRAE and no grade 5 TRAEs. The TRAEs were predominantly transient injection site reactions.
Addressing the HPV16-Positive HNSCC Population
Findings from outreach to key opinion leaders and oncologists indicate that at least 50% of head and neck cancer patients are HPV positive, with the percentage increasing. Experts in the United States and Europe report that over 70% of new patients they see are HPV 16 positive, confirming the rapid increase in this population. HPV positive head and neck cancers are virally driven cancers and are increasingly seen as a different disease from HPV negative head and neck cancer with a different tumor physiology. An HPV targeted approach is believed to offer the best potential for more effective therapy.
Companion Diagnostic for Patient Selection
The VERSATILE-003 trial will utilize a recently validated companion diagnostic to confirm HPV16-positive HNSCC during patient screening. According to Dr. Kirk Shepard, Chief Medical Officer of PDS Biotech, confirming HPV16 status with a potentially commercializable test is essential to effectively identifying the patients suitable to receive Versamune HPV. This will be the first investigational use of this type of companion diagnostic in a Phase 3 clinical trial in HNSCC.
Financial Update
For the third quarter of 2024, PDS Biotech reported a net loss of approximately $10.7 million, or $0.29 per basic and diluted share. Research and development expenses increased to approximately $6.8 million, primarily due to higher manufacturing expenses. As of September 30, 2024, the company's cash and cash equivalents totaled approximately $50 million.
IMMUNOCERV Trial Data
Data from the IMMUNOCERV Phase 2 clinical trial evaluating Versamune HPV with chemoradiation to treat locally advanced cervical cancer, presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting, demonstrated promising clinical activity and a compelling safety profile. In patients who received all five doses of Versamune HPV, the 36-month overall survival rate was 100%.
