Versamune HPV–Based Immunotherapy Combo Demonstrates Benefit in Advanced HPV-Associated Cancers

Treatment with the combination of the human papillomavirus type 16 (HPV-16) therapeutic vaccine Versamune HPV (formerly PDS0101); the IL-12 fused antibody-drug conjugate (ADC) PDS01ADC; and the bifunctional anti–PD-L1/TGF-β therapy bintrafusp alfa generated clinical benefit in patients with locally advanced or metastatic HPV-associated cancers, including anal, cervical, head and neck, penile, vaginal, and vulvar malignancies, according to data from a phase 1/2 trial (NCT04287868).1,2

Findings published in JAMA Oncology showed that among patients who were HPV16-positive and naive to an immune checkpoint inhibitor (n = 8), the median overall survival (OS) was not yet reached, and this population experienced a confirmed objective response rate (ORR) of 62.5% (95% CI, 24.5%-91.5%); an additional patient who achieved a response by per Immune-Related RECIST criteria pushed the ORR to 75% (95% CI, 34.9%-96.8%).1 Among all patients naive to an immune checkpoint inhibitor, regardless of HPV16 status (n = 14), the median OS was 42.4 months (95% CI, 8.3-not estimable).

In HPV16-positive patients who experienced disease progression on a prior immune checkpoint inhibitor (n = 29), the median OS was 17.0 months (95% CI, 10.4-22.8), and the ORR was 20.7%. In all patients previously exposed to an immune checkpoint inhibitor (n = 36), the median OS was 15.8 months (95% CI, 9.0-21.3), and the ORR was 16.7% (95% CI, 6.4%-32.8%).

“These results underscore the clinical potential of Versamune HPV—an HPV16-targeted immunotherapy—when used in combination with PDS01ADC and an immune checkpoint inhibitor in transforming the treatment paradigm for HPV-associated cancers,” Frank Bedu-Addo, PhD, president and chief executive officer of PDS Biotech, stated in in a news release.2

Phase 1/2 Study Design and Enrollment Criteria

The nonrandomized trial enrolled patients at least 18 years of age with histologically confirmed locally advanced or metastatic HPV-associated cancers or HPV-positive cancers who had measurable disease per RECIST 1.1 criteria; an ECOG performance status of 0, 1, or 2; and adequate organ function.1 Disease progression after at least 1 prior line of systemic therapy was required, or patients needed to be ineligible for or decline standard treatment.

Initially, patients were excluded if they had received prior immune checkpoint blockade; however, protocol modifications later allowed prior immune checkpoint inhibition, and subsequent changes required prior treatment with an immune checkpoint inhibitor due to changes in the standard-of-care, first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and cervical cancer. Positive HPV status was not required for enrollment.

All enrolled patients received a combination regimen consisting of:

• 1200 mg of intravenous bintrafusp alfa every 2 weeks (initially allowing reduced starting doses of 600 mg or 300 mg)
• 16.8 µg/kg of subcutaneous PDS01ADC every 4 weeks (or 8 µg/kg every 2 weeks)
• 1 mL of Versamune HPV subcutaneously every 4 weeks for 6 doses, followed by every 12 weeks for 2 additional doses

Treatment continued until disease progression, unacceptable toxicity, consent withdrawal, or completion of 1 year; however, treatment with PDS01ADC and bintrafusp alfa could continue beyond 1 year. Dose modifications were permitted, including Versamune HPV discontinuation in patients with HPV-16–negative tumors and dose reductions for bintrafusp alfa and PDS01ADC to manage adverse effects (AEs).

The trial’s primary end point was ORR per RECIST 1.1 criteria in patients with immune checkpoint inhibitor–naive HPV-associated cancers. Secondary end points included progression-free survival (PFS), OS, and safety assessments.1

Exploratory analyses included ORR per Immune-Related RECIST criteria; ORR in patients with immune checkpoint inhibitor–resistant HPV-associated cancers; ORR by HPV serotype and dose level of PDS01ADC or bintrafusp alfa; and circulating HPV-16–specific T-cell responses.

Enrolled patients (n = 50) had a median age of 56 years (range, 28-80), and 52% were male. Tumor types included oropharyngeal (42%), cervical (28%), anal/rectal (20%), vulvar/vaginal (6%), nasopharyngeal (2%), and penile (2%). Patients received 1 prior line of therapy (10%), 2 prior lines of therapy (44%), or 3 or more lines of therapy (46%). Ninety percent of patients underwent prior radiotherapy, and 72% received a prior immune checkpoint inhibitor.

At baseline, 74% of patients were HPV-16 positive; 22% of patients were positive for HPV other than HPV-16; 2% of patients were HPV negative; and HPV status was unknown in 2% of patients.

Safety Considerations

Treatment-related AEs (TRAEs) of any grade occurred in all patients (n = 50); the rate of grade 3 or 4 TRAEs was 52%. The most frequently observed TRAEs included injection-site reactions (any-grade, 72%; grade ≥3, 0%), flu-like symptoms (64%; 0%), anemia (52%; 26%), gingival bleeding (34%; 0%), fatigue (32%; 0%), hematuria (24%; 10%), epistaxis (24%; 0%), increased aspartate aminotransferase levels (24%; 6%), maculopapular rash (22%; 0%), pruritus (22%; 0%), oral mucositis (22%; 0%), decreased lymphocyte count (20%; 8%), nausea (18%; 0%), headache (16%; 0%), increased alanine aminotransferase levels (14%; 6%), vomiting (14%; 0%), increased alkaline phosphatase levels (12%; 0%), mucosal bleeding (12%; 4%), keratoacanthoma (10%; 0%), decreased white blood cell count (10%; 0%), acneiform rash (10%; 0%), and fever (10%; 0%).

Serious TRAEs occurred in 26% of patients. TRAEs leading to treatment discontinuation occurred in 24%; the most common TRAEs leading to discontinuation included liver function test abnormalities (6%), bleeding (6%)—including gastric bleeding, anal bleeding, and hematuria—anemia (2%), myocarditis (2%), myositis (2%), pneumonitis (2%), colitis (2%), and gastroparesis (2%).

Any-grade mucosal bleeding AEs associated with bintrafusp alfa occurred in 70% of patients, and the rate of grade 3 effects reported in 18%. No grade 4 or higher mucosal bleeding was observed, and no treatment-related deaths occurred.

“[HPV-associated] cancers include 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,” Bedu-Addo added in the news release.2 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 [phase 3] VERSATILE-003 3 trial [NCT06790966] of Versamune HPV plus pembrolizumab [Keytruda] in recurrent/metastatic HPV16-positive HNSCC [in March 2025].2

References

1. Floudas CS, Goswami M, Donahue RN, et al. Novel combination immunotherapy and clinical activity in patients with HPV-associated cancers. JAMA Oncology. Published online February 20, 2025. doi:10.1001/jamaoncol.2024.6998
2. PDS Biotech announces positive clinical data demonstrating compelling survival and clinical responses in recurrent/metastatic HPV-associated cancers published in JAMA Oncology. News release. PDS Biotechnology. February 26, 2025. Accessed March 4, 2025. https://pdsbiotech.com/index.php/investors/news-center/press-releases/press-releases1/132-2025-news/971