Human papillomavirus (HPV)-associated malignancies continue to present a major health concern despite the development of prophylactic vaccines.[1][2]
Cancers such as head and neck, cervical, anal, penile, vaginal, vulvar that are caused by HPV infection can be identified through tissue examination or biopsy and imaging (CT, PET X-ray, MRI).
Currently HPV-positive cancers are treated with surgery, chemotherapy, radiation and immunotherapies such as checkpoint inhibitors, either alone or in combination. However, there remains a high unmet need for more effective, safer, better tolerated and HPV-targeted treatment options [2][3][4]
Head and Neck Cancer
HPV-associated head and neck squamous cell carcinoma (HNSCC) represents a major public health concern in the United States.
According to the American Cancer Society HNSCC accounts for approximately 4% of all new cancer cases annually, with an estimated 66,000 new diagnoses each year. Although these cancers can affect individuals of any age, they are generally more frequently diagnosed in older adults, with the average age at diagnosis typically around 60 to 70 years.
The majority of patients diagnosed with HNSCC, will present with locally advanced disease, which requires a multimodality therapy. Although this approach has a curative intent, a significant subset of patients will develop locoregional failure and/or distant metastases. The prognosis of these patients remains poor, and represent a major unmet medical need.
In 2016, the anti-programmed death-1 (PD-1) immune checkpoint inhibitors nivolumab (Opdivo®; Bristol-Myers Squibb) and pembrolizumab (Keytruda®; Merck & Co/MSD) were both approved for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy. Later, in 2019, pembrolizumab was approved for first-line treatment, either as monotherapy in PD-L1 expressing tumors, or in combination with chemotherapy.
Pembrolizumab has been shown to have efficacy against both HPV-positive and HPV-negative head and neck cancers. However, its effectiveness is more optimal in tumors that are PD-L1 positive and have evidence of immune cells within the tumor
Despite improved outcomes with programmed cell death protein-1 (PD-1) targeted therapies, treatment resistance and modest response rates highlight a significant unmet medical need, requiring the development of novel therapies for these patients. This is especially critical for patients with advanced-stage disease.
New treatment options
Ongoing development include immune checkpoint inhibition in the (neo)adjuvant treatment of HNSCC as well as in novel combinations with other drugs in the recurrent/metastatic setting to improve response rates and survival and help overcome resistance mechanisms to immune checkpoint blockade.
PDS0101 is a novel investigational liposomal nanoparticle T-cell HPV16-specific targeted immunotherapy delivered subcutaneously that has been shown to stimulate high levels of HPV16-specific CD8+ and CD4+ T cells within patients by activating multiple immune pathways. These HPV-specific T cells then target tumors such as head and neck, anal and cervical cancers that are caused by HPV infection. PDS0101 has shown to generate strong HPV-specific responses in preclinical and clinical studies.
PDS0101is being investigated in combination with pembrolizumab in patients with HPV16-positive first-line recurrent and/or metastatic head and neck squamous cell cancer (1L R/M HNSCC), shows promising results.
Clinical data suggest these immunotherapies demonstrate significant disease control by shrinking tumors, delaying disease progression and/or prolonging survival.
VERSATILE-002 Study
Final top-line survival data from the VERSATILE-002 (NCT04260126), an open-label, multi-center Phase 2 clinical trial evaluating the safety and efficacy of PDS0101.
The study results show a median overall survival (mOS) is 39.3 months in patients with CPS ≥ 1. The lower limit of the 95% confidence interval is 23.9 months, and the upper limit is not yet estimable. Durable patient survival is promoted by high levels of long-lasting, multifunctional HPV16-specific CD8+ T cells induced by PDS0101 and was similar across patient demographics and clinical characteristics such as age, CPS status, and prior treatment.
“We believe this final readout of top-line survival data from our VERSATILE-002 clinical trial supports the durable clinical effect of PDS0101 with similarly promising survival outcomes reported in two other recently published studies, the IMMUNOCERV study, and the NCI-led study in HPV16-positive recurrent and/or metastatic cancers,” noted Kirk Shepard, MD, Chief Medical Officer of PDS Biotechnology.
“We believe PDS0101, which is simple and easy to administer, brings new hope to the rapidly growing population of HPV16-positive head and neck cancer patients. We look forward to publishing the full data set for this trial later this year,” Shepard added.
A growing segment
“With these results, PDS Biotechnology is well positioned for leadership in the largest and most rapidly growing segment of HNSCC in the US and Europe. HPV16-positive HNSCC constitutes a significant and rapidly growing unmet medical need, and a targeted therapy to treat the underlying cause of the disease is urgently needed. We believe that oncologists will continue to prioritize therapies that give their patients the best chance for survival. With PDS0101 plus pembrolizumab, an added benefit appears to be that the combination is well tolerated, and no patients discontinued the trial due to treatment-related adverse events,” explained Frank Bedu-Addo, PhD, President and Chief Executive Officer of PDS Biotechnology.
*No head-to-head studies have been performed comparing pembrolizumab and PDS0101
Clinical trials
Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies – ClinicalTrials.gov ID NCT04287868
Study of PDS0101 and Pembrolizumab Combination I/O in Subjects with HPV16 + Recurrent And/or Metastatic HNSCC (VERSATILE002)
ClinicalTrials.gov ID NCT04260126
A Vaccine (PDS0101) and Chemoradiation for the Treatment of Stage IB3-IVA Cervical Cancer, the IMMUNOCERV Trial – ClinicalTrials.gov ID NCT04580771
Highlights of Prescribing Information
Nivolumab (Opdivo®; Bristol-Myers Squibb)[Prescribing Information]
Pembrolizumab (Keytruda®; Merck & Co/MSD)[Prescribing Information]
Reference
[1] Joseph AW, D’Souza G. Epidemiology of human papillomavirus-related head and neck cancer. Otolaryngol Clin North Am. 2012 Aug;45(4):739-64. doi: 10.1016/j.otc.2012.04.003. Epub 2012 May 31. PMID: 22793850.
[2] Viens LJ, Henley SJ, Watson M, Markowitz LE, Thomas CC, Thompson TD, Razzaghi H, Saraiya M. Human Papillomavirus-Associated Cancers – United States, 2008-2012. MMWR Morb Mortal Wkly Rep. 2016 Jul 8;65(26):661-6. doi: 10.15585/mmwr.mm6526a1. PMID: 27387669.
[3] Liao CI, Francoeur AA, Kapp DS, Caesar MAP, Huh WK, Chan JK. Trends in Human Papillomavirus-Associated Cancers, Demographic Characteristics, and Vaccinations in the US, 2001-2017. JAMA Netw Open. 2022 Mar 1;5(3):e222530. doi: 10.1001/jamanetworkopen.2022.2530. PMID: 35294540; PMCID: PMC8928005.
[4] Senkomago V, Henley SJ, Thomas CC, Mix JM, Markowitz LE, Saraiya M. Human Papillomavirus-Attributable Cancers – United States, 2012-2016. MMWR Morb Mortal Wkly Rep. 2019 Aug 23;68(33):724-728. doi: 10.15585/mmwr.mm6833a3. PMID: 31437140; PMCID: PMC6705893.
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