First-Line Versamune HPV Plus Pembrolizumab Meets BOR End Point in Recurrent/Metastatic HPV16+ HNSCC

First-line treatment with the combination of Versamune HPV (PDS0101) and pembrolizumab (Keytruda) met the primary end point of best overall response (BOR) in the phase 2 VERSATILE-002 trial (NCT04260126) of patients with human papillomavirus (HPV)16–positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).¹

Findings announced by PDS Biotechnology showed that the combination elicited a BOR of 34% in a cohort of patients who were naive to immune checkpoint inhibitors and had a PD-L1 combined positive score (CPS) of at least 1 (n = 53). In patients with a PD-L1 CPS of at least 20 (n = 21), the BOR was 48%.

Additionally, the population of patients with a PD-L1 CPS of at least 1 achieved a median overall survival (OS) of 30 months. The median progression-free survival (PFS) was 6.3 months for the population of patients with a PD-L1 CPS of at least 1 and 14.1 months in those with a PD-L1 CPS of at least 20.

“VERSATILE-002 data to date indicate a durable response in [patients with] first-line recurrent and/or metastatic HNSCC with a CPS of at least 1,” PDS Biotechnology wrote in a news release.

The open-label, multicenter VERSATILE-002 study enrolled patients who were at least 18 years of age with histologically confirmed, recurrent, metastatic, or persistent HNSCC and a confirmed HPV16 infection. Patients needed to have a confirmed PD-L1 CPS of at least 1.²

In the checkpoint inhibitor–naive cohort, no prior immunological therapy for metastatic disease was allowed. In the pretreated cohort, patients needed to have prior treatment with checkpoint inhibitors as monotherapy or in a combination; at least 2 doses or a minimum of 6 weeks on treatment were required. These patients also needed documented and radiologically confirmed clinical progression or recurrence.

Other key inclusion criteria for all patients included recurrent and/or metastatic disease per RECIST 1.1 criteria; adequate organ function; an ECOG performance status of 0 or 1; and recovery from toxicities associated with prior radiation.

Patients who received a prior checkpoint inhibitor or T-cell receptor–directed agent and discontinued treatment due to grade 3 or higher adverse effects were excluded. Prior anticancer therapy in the 30 days before enrollment was not allowed. Other key exclusion criteria included known active central nervous system metastases and/or carcinomatosis meningitis; prior allogeneic hematopoietic stem cell transplantation within the last 5 years; active autoimmune disease that has required systemic treatment in the past 2 years; and a history of non-infectious pneumonitis requiring steroids or current pneumonitis.

All patients received 2 subcutaneous injections of Versamune HPV at 0.5 mL during cycles 1, 2, 3, 4, and 12. Pembrolizumab was administered at 200 mg once every 3 weeks, and was given both in combination with Versamune HPV and as a monotherapy during cycles 5 to 11 and 13 to 35.

BOR—comprising confirmed complete responses and confirmed partial responses—per RECIST 1.1 criteria served as the trial’s primary end point. Secondary end points included PFS per RECIST 1.1 criteria, OS, and safety. Other end points included duration of response and anti-HPV16 E6 and E7 immune responses.

Safety data showed that Versamune HPV plus pembrolizumab was well tolerated.¹

A two-part registrational trial will utilize a combination therapy consisting of Versamune HPV, pembrolizumab, and PDS01ADC as a first-line treatment for patients with HPV16-positive recurrent/metastatic HNSCC. PDS01ADC is a novel, investigational, tumor-targeting IL-12–fused antibody-drug conjugate.

The first part will be a dose-optimization study with end points based on safety and objective response rate. The second part of the trial will be randomized with OS as its primary end point.

References

1. PDS Biotech VERSATILE-002 phase 2 clinical trial meets primary study endpoints in first line recurrent/metastatic HPV16-positive head and neck cancer. News release. PDS Biotechnology. May 9, 2024. Accessed May 10, 2024. https://pdsbiotech.com/index.php/investors/news-center/press-releases/press-releases1/131-2024-news/918-iotech002hase2linicalrialeetsrim20240509
2. Study of PDS0101 and pembrolizumab combination I/​O in subjects with HPV16 + recurrent and/​or metastatic HNSCC (VERSATILE002). ClinicalTrials.gov. Updated March 15, 2024. Accessed May 10, 2024. https://clinicaltrials.gov/study/NCT04260126