PDS Biotech Updates Phase 3 VERSATILE-003 Trial Design for HPV16-Positive HNSCC

• PDS Biotechnology has updated the Phase 3 VERSATILE-003 trial design for HPV16-positive recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC), increasing the patient target to approximately 350.
• The updated design maintains a 2:1 randomization and median overall survival as the primary endpoint, aligning with the FDA agreement on registrational design.
• The revised trial design allows for potential earlier interim readouts, faster study completion, and reduced execution costs, while retaining statistical power.
• VERSATILE-002 results have demonstrated durable anti-tumor responses, influencing the design updates for VERSATILE-003 and showing improved clinical responses over time.

PDS Biotechnology Corporation has announced an update to the Phase 3 VERSATILE-003 trial design, focusing on patients with HPV16-positive first-line recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). The revised design aims to enhance trial efficiency and maintain statistical rigor while assessing the efficacy of their lead candidate.

Trial Design Modifications

The updated VERSATILE-003 trial now plans to enroll approximately 350 patients. This adjustment follows observations from the VERSATILE-002 trial, which demonstrated broadly improving clinical responses across multiple parameters, with increased patient size and duration of follow-up over the past year, indicating durability of anti-tumor responses.

The design retains a 2:1 randomization scheme and maintains median overall survival (mOS) as the primary endpoint. These elements are consistent with PDS Biotech's agreement with the FDA regarding registrational design. An amended IND (Investigational New Drug application) reflecting the updated design was submitted in November 2024.

Potential Benefits of the New Design

According to PDS Biotech, the updated design offers several potential advantages, including:

• Potential for earlier interim readouts
• Potential for faster study completion
• Potential for reduced execution costs

These modifications are intended to streamline the trial process without compromising the integrity of the study's primary endpoint or statistical power.

Clinical Context

Head and neck squamous cell carcinoma (HNSCC) represents a significant clinical challenge, particularly in recurrent or metastatic settings. HPV16-positive HNSCC is a distinct subtype with unique characteristics and treatment responses. The VERSATILE-003 trial aims to address the unmet need for effective first-line treatments in this patient population. The VERSATILE-002 trial results have shown broadly improving clinical responses across multiple parameters with increases in patient size and duration of patient follow up over the last year, demonstrating durability of the anti-tumour responses. The design, which is informed by the observed durability of the clinical responses, retains statistical power and remains within the confines of PDS Biotech's agreement with the FDA on registrational design.