JAMA Publishes Versamune HPV Study Results

The article demonstrates the promising clinical responses seen with the triple combination of Versamune HPV (formerly PDS 0101), the Company’s IL-12 fused antibody-drug conjugate, PDS01ADC and a PD-L1 immune checkpoint inhibitor (ICI), in patients with recurrent/metastatic HPV-associated cancers. Patients enrolled in the trial had anal, cervical, head and neck, penile, vaginal and vulvar cancers.

“These results underscore the clinical potential of Versamune HPV—an HPV16-targeted immunotherapy—when used in combination with PDS01ADC and an ICI in transforming the treatment paradigm for HPV-associated cancers,” said Frank Bedu-Addo, PhD, President and Chief Executive Officer of PDS Biotech. “This group of cancers includes rare cancers such as anal, penile, vaginal and vulvar cancers, and it also includes growing, higher incidence cancers such as head and neck cancer. An increasing number of head and neck cancers, including a majority of oropharyngeal cancers, are now reported to be HPV16-positive. Based on these impressive peer-reviewed results demonstrating the strong potential of Versamune HPV as an HPV16-targeted immunotherapy, we are excited to begin our VERSATILE-003 Phase III trial of Versamune  HPV + pembrolizumab in recurrent/metastatic HPV16-positive head and neck squamous cell carcinoma next month. The study also demonstrates the strength of our pipeline combination therapies that may build upon the reported potential of Versamune HPV + standard of care.”

The single-center, non-randomized clinical trial, led by the National Cancer Institute (NCI), evaluated Versamune  HPV + PDS01ADC + bintrafusp alfa (BA) in patients with recurrent/metastatic HPV-positive cancers. Of the 50 enrolled patients, 26 (52%) were men, the median age was 56 years (range, 28-80 years), and 37 patients were HPV16-positive. The median follow-up time was 37.7 (0.6-42.0) months. All patients had recurrent/metastatic disease and had progressed after prior treatment. 46% of patients had at least 3 rounds of prior treatment. 72% of patients had failed prior ICI therapy. Versamune HPV was evaluated at a fixed dose. PDS01ADC was evaluated at a 16.8ug/kg dose (high) and a 8.0 ug/kg dose (low). BA was also administered at a high and low dose.

The trial results confirm previously published results from a preclinical study of the triple combination performed by the NCI. The preclinical study demonstrated that when Versamune HPV is administered in conjunction with PDS01ADC and/or an ICI, the CD8 killer T cell immune response is significantly amplified, and specifically directed to attack HPV16-positive tumors.

Published Clinical Results:

Immune checkpoint blockade (ICB) naïve patients (no prior exposure to checkpoint inhibitors): N = 14

• i. ORR for the group was 35.7% (95% CI, 12.8%-64.9%)
  • ii. Among 8 HPV16-positive patients, the confirmed ORR was 62.5% by RECISTv1.1 and 75% by irRECIST
  • The historically published result for this group of patients with standard-of-care immune checkpoint inhibitors is 12-24%
    
     
• i.Median overall survival (mOS) for the group was 42.4 months (95% CI, 8.3 months—not estimable);
  • ii Among 8 HPV16-positive patients, the mOS has not yet been reached.
  • The historically published result with standard-of-care is 7-12 months
     

ICB-resistant patients (disease progression after treatment with ICI): N = 36:

• i. ORR for the group was 16.7% (95% CI, 6.4%-32.8%)
  • ii. Among 29 HPV16-positive patients, the confirmed ORR was 20.7%;
    • iii. Among 8 HPV16-positive patients who received the 16.8ug/kg dose of PDS01ADC, the confirmed ORR was 62.5%.
  • The historically published result is 10%
  •  
• i. Median overall survival (mOS) for the group was 15.8 months (95% CI, 9.0-21.3 months).
  • ii. Among 29 HPV16-positive patients treated at all dose levels, the median OS was 17.0 months;
  • The historically published result is 3-4 months, and there is no FDA-approved standard-of-care
    
     
• Grade 3 and 4 treatment-related adverse events occurred in 26 of 50 patients (52%), and toxicity correlated with the dose of PDS01ADC and BA. There were no treatment-related deaths.

Citation:Novel Combination Immunotherapy and Clinical Activity in Patients With HPV-Associated Cancers;A Nonrandomized Clinical Trial.;Charalampos S. Floudas, MD, DMSc, MS; Meghali Goswami, PhD; Renee N. Donahue, PhD; et al . JAMA Oncol. Published online February 20, 2025. doi:10.1001/jamaoncol.2024.6998.