PDS Biotech recently announced the initiation of a Phase III pivotal trial for its immunotherapy asset PDS0101 in recurrent/metastatic HPV-16+ head and neck squamous cell carcinoma (HNSCC). If approved, PDS0101 could reach $500 million in 8MM* sales in metastatic HNSCC, but the current lack of data for HPV-positive patients endangers the outcome of the Phase III study, according to GlobalData, a leading data and analytics company.

Sakis Paliouras, PhD, Associate Director, Oncology & Hematology at GlobalData, comments: “The VERSATILE-002 trial enrolled 54 recurrent or metastatic HNSCC patients with CPS ≥ 1 who were treated with Keytruda + PDS0101. The most interesting result was that 74% of patients treated with the combination were alive after two years. This is substantially higher than Keytruda + chemotherapy’s 2-year overall survival (OS) of 30.8%. It is also encouraging that the addition of PDS0101 did not substantially increase high-grade adverse events.”

Previously, the Phase III KEYNOTE-048 study established Merck & Co’s Keytruda as the standard of care in this patient population with or without chemotherapy, dethroning Eli Lilly’s Erbitux. In KEYNOTE-048, patients with a PD-L1 combined positive score (CPS) ≥ 1 treated with Keytruda monotherapy saw a 12.3-month median overall survival (OS) and 13.6 months for patients treated with Keytruda + chemotherapy.

Paliouras continues: “These results will allow PDS Biotech to initiate a Phase III randomized trial of PDS0101 + Keytruda in Q1 2024. A threat to Phase III success is that historically, HPV+ HNSCC patients had more favorable outcomes. Crucially, the KEYNOTE-48 study enrolled 471 HPV-negative patients and only 130 HPV+ patients. Thus, it is very likely that the benefit of Keytruda ± chemotherapy was much larger for HPV+ patients in KEYNOTE-048 but was diluted by over three times as many HPV-negative patients. The margin of benefit is unknown since no HPV subgroup OS analysis was performed.”

A 2014 analysis of the Radiation Therapy Oncology Group showed that patients with HPV-16+ disease had a roughly double 2-year OS (54.6%) versus 27.6% for HPV-16-negative patients after progression on systemic chemotherapy.

Paliouras concludes: “While this immunotherapy can be clinically successful if approved, commercial sales will be challenged by HPV positivity. A 2005 meta-analysis by the International Agency for Research on Cancer (IARC) suggests that 25.9% of all HNSCC cases are HPV+, the majority of which are HPV-16. As such, PDS0101 would have a roughly four-times smaller total addressable market compared to Keytruda. Previous GlobalData forecasts estimated Keytruda’s HNSCC sales in the 8MM to reach $2.1 billion by 2029, suggesting a potential $500 million ceiling in HNSCC revenue for PDS Biotech if PDS0101 was approved.”

*8MM (The US, France, Germany, Italy, Spain, the UK, Japan, and China)