PDS0101 + Pembrolizumab for Head and Neck Cancer

(VERSATILE002 Trial)

No longer recruiting at 28 trial locations

Overseen By Sally Jones

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: PDS Biotechnology Corp.

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Pregnancy, Active infection, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: Up to 35 cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with head and neck cancer that has recurred or spread and is associated with HPV16 and PD-L1 proteins. The treatment involves two drugs: PDS0101, administered as an injection, and pembrolizumab (also known as KEYTRUDA or MK-3475), given through an IV. The study aims to evaluate the effectiveness and safety of these drugs when used together. It seeks participants with HPV16-positive head and neck cancer that has returned or spread and who have not yet received certain immune-based treatments for this condition. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received certain treatments like systemic anti-cancer therapy or immunotherapy within 30 days before starting the trial. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining PDS0101 with pembrolizumab holds promise for treating head and neck cancer. Previous studies suggest that patients generally tolerate this combination well. On average, patients have lived for 39.3 months, which is encouraging.

Pembrolizumab alone is already approved for treating some cancers, indicating it has undergone safety testing in humans. While the combination with PDS0101 remains under study, no new major safety concerns have emerged so far. Always consult a healthcare provider to understand the implications of joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PDS0101 combined with Pembrolizumab for head and neck cancer because it offers a unique approach compared to standard treatments like surgery, radiation, and chemotherapy. PDS0101 is a novel immunotherapy that works by activating the immune system to target cancer cells more effectively. When combined with Pembrolizumab, a known immune checkpoint inhibitor, this combination has the potential to enhance the body’s immune response against cancer more powerfully than existing therapies. This approach not only aims to improve treatment efficacy but also seeks to offer a more targeted attack on cancer cells with potentially fewer side effects.

What evidence suggests that PDS0101 and pembrolizumab could be effective for head and neck cancer?

Research has shown that using PDS0101 with pembrolizumab could be promising for treating head and neck cancer. In one study, patients with HPV16-positive head and neck cancer who received this combination lived for a median of 39.3 months, compared to 10.8 months for those who only received pembrolizumab. While pembrolizumab alone works for some head and neck cancers, results improve when combined with PDS0101. In this trial, participants will receive both pembrolizumab and PDS0101, potentially offering a stronger way to manage the disease. ^{1 3 4 6 7}

Who Is on the Research Team?

David T Schaaf, MD

Principal Investigator

PDS Biotechnology Corporation

Are You a Good Fit for This Trial?

Adults over 18 with HPV16 and PD-L1 positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who've had prior checkpoint inhibitor treatment can join. They need measurable disease, adequate organ function, no recent major surgery or radiation without recovery, not pregnant or breastfeeding, willing to use contraception, and have an ECOG status of 0-1.

Inclusion Criteria

I am not pregnant, can use birth control during the study, and if male, will use a condom.

Participant (or legally acceptable representative if applicable) provides written informed consent for the study

My cancer is HPV16 positive, has PDL1 expression, and I haven't had immunotherapy.

Exclusion Criteria

Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients

I have a history of lung scarring or fibrosis.

I had a stem cell transplant from a donor within the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab via IV infusion and PDS0101 via subcutaneous injections. Pembrolizumab monotherapy is administered every cycle without combination treatment until disease progression or up to Cycle 35.

Up to 35 cycles

5 visits for PDS0101 injections, additional visits for pembrolizumab monotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, including overall survival and progression-free survival assessments.

24 months

Extension/Long-term follow-up

Participants may continue to be monitored for overall survival and duration of response.

Up to 35 months

What Are the Treatments Tested in This Trial?

Interventions

• PDS0101
• Pembrolizumab

Trial Overview The VERSATILE-002 Phase 2 trial is testing the effectiveness and safety of PDS0101 in combination with pembrolizumab for treating adults with HPV16+ HNSCC that has come back or spread. It's open-label and multicenter, meaning both researchers and participants know what treatment is being given.

How Is the Trial Designed?

Group I: Pembrolizumab and PDS0101 Experimental Treatment 1 Intervention

Pembrolizumab will be administered via IV Infusion followed by subcutaneous injections of PDS0101 five times throughout the course of the study. Pembrolizumab monotherapy will be administered every cycle there is not a combination treatment until disease progression or up to Cycle 35.

Who Is Running the Clinical Trial?

PDS Biotechnology Corp.

Lead Sponsor

Trials

3

Recruited

460+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a phase 1b trial involving 60 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, pembrolizumab was found to be well tolerated, with only 17% experiencing severe drug-related adverse events and no drug-related deaths.

The treatment showed clinically meaningful antitumor activity, with an overall response rate of 18%, and particularly higher in HPV-positive patients at 25%, indicating its potential as a viable therapy for advanced head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Seiwert, TY., Burtness, B., Mehra, R., et al.[2022]

In a study involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

In a study of 34 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with PD-1 inhibitors, 29% experienced hyperprogression, where tumor growth accelerated during treatment.

Hyperprogression was significantly associated with regional recurrence, leading to shorter progression-free survival, but did not affect overall survival, highlighting the need for further research into the mechanisms behind this phenomenon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Saâda-Bouzid, E., Defaucheux, C., Karabajakian, A., et al.[2022]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

In a phase 3 study involving 495 patients with recurrent or metastatic head-and-neck squamous cell carcinoma, pembrolizumab demonstrated a median overall survival of 8.4 months, compared to 6.9 months for standard-of-care treatments, indicating a significant improvement in survival rates.

Pembrolizumab was associated with fewer severe treatment-related adverse events (13%) compared to standard-of-care therapies (36%), suggesting a better safety profile for patients receiving pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Cohen, EEW., Soulières, D., Le Tourneau, C., et al.[2019]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

In a phase III trial, pembrolizumab, a single-agent treatment, showed significant effectiveness in patients with head and neck tumors that had high PD-L1 expression, leading to deep and lasting responses.

This study highlights the potential of pembrolizumab as a first-line therapy for this specific group of cancer patients, suggesting a targeted approach based on PD-L1 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembro Ups Survival in PD-L1-positive HNSCC. [2019]

Citations

1. pdsbiotech.com pdsbiotech.com/index.php/investors/news-center/press-releases/press-releases1/132-2025-news/1018-pds-biotech-sets-significant-benchmark-in-head-and-neck-canc2025-09-18-055003

News Center First combination therapy to report 29.5 months of Median Overall Survival (mOS); Standard of care Keytruda® (pembrolizumab) alone (10.8 ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6037

Versatile-002: Overall survival of HPV16-positive recurrent/ ... Safety and efficacy of immune checkpoint inhibitor (ICI) naïve cohort from study of PDS0101 and pembrolizumab in HPV16-positive head and neck ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04260126

NCT04260126 | Study of PDS0101 and Pembrolizumab ... 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 ...

4. cancernetwork.com cancernetwork.com/view/pds0101-plus-pembrolizumab-yields-positive-survival-results-in-hnscc

PDS0101 Plus Pembrolizumab Yields Positive Survival ... The median overall survival was 39.3 months with PDS0101 plus pembrolizumab in those with frontline recurrent or metastatic head and neck ...

5. onclive.com onclive.com/view/pds0101-plus-pembrolizumab-yields-durable-survival-benefit-in-hpv16-hnscc

PDS0101 Plus Pembrolizumab Yields Durable Survival ... Versamune HPV (formerly PDS0101) in combination with pembrolizumab (Keytruda) generated a median overall survival (OS) of 39.3 months (95% ...

6. pdsbiotech.com pdsbiotech.com/index.php/investors/news-center/press-releases/press-releases1/132-2025-news/1016-pds-biotech-announces-final-topline-survival-data-fromvers2025-08-25-053503

PDS Biotech Announces Final Topline Survival Data from ... Median Overall Survival (mOS) of 39.3 months in patients with CPS ≥ 1 – best published result with standard of care pembrolizumab or ...

7. yalemedicine.org yalemedicine.org/clinical-trials/pds0101-hnc-301-a-phase-3-open-label-randomized-study-of-pds0101-plus-pembrolizumab-vs-pembrolizum

A Phase II, Open-Label, Multi-Center Study of PDS0101 ... Pembrolizumab has been shown to have efficacy against both HPV-positive and HPV-negative head and neck cancers. However, its effectiveness is ...