First-Line Versamune HPV Vaccine Bolsters Responses With SOC Pembrolizumab in HPV16+ Recurrent HNSCC

Jared Weiss, MD

Adding the novel therapeutic cancer vaccine Versamune HPV (PDS0101) to standard pembrolizumab (Keytruda) could produce robust, durable responses and improve survival outcomes in the first line for patients with human papillomavirus (HPV)16–positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to Jared Weiss, MD.

Updated data from the phase 2 VERSATILE-002 trial (NCT04260126) presented at the 2024 ESMO Congress showed that the regimen was well-tolerated and produced high clinical activity. At a data cutoff of May 17, 2024, and a median follow-up of 16 months, patients with a combined positive score of 1 or higher (n = 53) achieved a median overall survival (OS) of 30 months (95% CI, 19.7-not evaluable) and a median progression-free survival of 6.3 months. The objective response rate was 35.8%, 9.4% of which were complete responses, and the disease control rate was 77.4%. Moreover, 21% of patients experienced tumor shrinkage between 90% and 100%. Twenty-seven patients continue to be followed for survival, 10 of whom remained on study treatment at the time of this analysis. Regarding safety, only 9 patients reported grade 3 or higher treatment-related adverse effects.

Findings support the continued evaluation of Versamune HPV plus pembrolizumab in the phase 3 VERSATILE-003 study (NCT04260126), which will compare the regimen with pembrolizumab monotherapy in HPV16-positive HNSCC.

“One exciting thing about the data presented here was that the survival improvement was not just in the median; the tail of the [OS] curve was substantially raised. If that is confirmed in the phase 3 study, it would change the SOC for recurrent metastatic disease and introduce a conversation about cure rate in this previously incurable [disease],” said Weiss, a professor of medicine in the Division of Oncology, Department of Medicine at the University of North Carolina (UNC) School of Medicine, as well as associate director for finance in the UNC Lineberger Clinical Protocol Office at the UNC Lineberger Comprehensive Cancer Center in Chapel Hill.

During an interview with OncLive®, Weiss discussed the need for better therapeutics in HPV-driven HNSCC due to the increasing risk of progression on curative therapies, detailed key results with the novel therapeutic HPV vaccine plus pembrolizumab in VERSATILE-002 trial, and emphasized the importance of validating the regimen’s efficacy and safety in a phase 3 trial.

OncLive: What unmet needs still exist for patients with HPV-driven HNSCC?

Weiss: [Unmet needs] are a bit lost in some of the conversation these days about HPV-driven HNSCC. The big story here is that these cancers are easier to cure, if you look at the landscape of locally advanced disease. If I meet an HPV-negative patient in clinic, I have a less than 50% chance of curing them. In contrast, if I meet a patient with HPV-driven cancer, I have over a 90% chance of curing them. At first glance, there wouldn’t seem to be an unmet need in the recurrent metastatic setting. The problem is that, because of slow uptake of preventive vaccination in pediatric populations, the epidemic of HPV-driven HNSCC will not peak until sometime in the 2030s. Although we may cure a larger proportion of patients, the denominator of patients at risk for [progressing on curative therapies] is rapidly rising. Consequently, these patients have an unmet need for better therapeutics.

What was the rationale for incorporating this therapeutic vaccine into first-line treatment with pembrolizumab in the VERSATILE-002 trial?

Viral-induced cancers provide a unique therapeutic vulnerability: cancer associated neoantigens. The Versamune HPV product is a therapeutic vaccine against this, comprising peptides against HPV16 E6 and E7 together with the strong adjuvant R-DOTAP.

VERSATILE-002 was a single-arm, nonrandomized phase 2study comprising standard-of-care [SOC] pembrolizumab with the added therapeutic vaccine product for cancers that were both PD-L1–positive and HPV16-positive.

What key findings from VERSATILE-002 were presented at the 2024 ESMO Congress?

The primary end point of the study was response rate. That was met and has been previously reported. The big findings presented at ESMO 2024 were [on] survival. [Survival] is one of the 2 key reasons, from a human perspective, that we treat [patients with] recurrent metastatic cancer. We want our patients to feel better and we want to preserve and ideally improve quality of life [QOL]. [QOL is] critically important, but very hard to measure. In contrast, our second important human end point is very objective: survival. Here, OS was an impressive 30 months.

Were any new or notable toxicities observed with the regimen?

The safety profile looks like what we expect from pembrolizumab alone, both as reflected in [the phase 3] KEYNOTE-048 trial [NCT02358031] as well as in day-to-day clinical practice. The only thing that was added here were injection site reactions. These occurred in most patients and were all grade 1 or 2.

What further investigations are planned for this regimen?

The purpose of this phase 2 study was to provide a go or no go signal for phase 3 [investigation]. This study met its primary end point and showed impressive survival with a nice tail to the curve. The consequence of that is not approval, but rather [continuation to] the phase 3 [VERSATILE-003] study, and that study is being planned.

What are the potential implications of this research?

When I was trained in HNSCC, I was taught that the cure rate for recurrent metastatic disease was essentially zero. That was happily violated with KEYNOTE-048, where we saw that we could provide durable control [with pembrolizumab]. Now, 10 years after phase 1, we can use the word ‘cure’ for a small but non-zero portion of the population. Ever since, the field of oncology research in general has been desperately seeking to raise that tail to provide a cure, or something that looks as close as possible to cure, to a greater proportion of patients.

Reference

Weiss J, Kaczmar J, Harrington KJ, et al. VERSATILE-002: survival with first-line treatment with PDS0101 therapeutic vaccine and pembrolizumab in HPV16-positive recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Ann Oncol. 2024;35(suppl 2):S628. doi:10.1016/j.annonc.2024.08.940