Phase 3 Study of PDS0101 and Pembrolizumab in HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Running, not enrolling · Phase 3

Conditions studied: Recurrent Head and Neck Cancer, Metastatic Head and Neck Cancer, HPV Positive Oropharyngeal Squamous Cell Carcinoma, Neoplasms, Head and Neck, Unresectable Head and Neck Squamous Cell Carcinoma

In brief

This is a global, multi-center, Phase 3 study that is randomized 1:1, controlled, and open label to evaluate PDS0101 (Versamune + HPVMix) in combination with pembrolizumab vs. pembrolizumab monotherapy as first-line treatment in patients with unresectable recurrent or metastatic HPV16-positive HNSCC expressing programmed cell death ligand-1 (PD-L1) with combined positive score (CPS) ≥1.

Key facts

Study ID: NCT06790966
Run by: PDS Biotechnology Corp.
People needed: 252
Starts: 2025-05-30
Expected to finish: 2029-02-01
Last updated by the study team: 2026-04-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Subject (or legally acceptable representative, if applicable) provides written informed consent for the study.
Subject is ≥18 years of age on the day of signing the informed consent.
Have a history of histologically- or cytologically-confirmed diagnosis of recurrent and/or metastatic squamous cell cancer of the head and neck (HNSCC) with:
Eligible primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx.
HPV16 tumor positivity (central testing).
Tumor PD-L1 expression defined as a CPS ≥ 1 using the FDA- approved pembrolizumab (KEYTRUDA®) assay (local testing).
No prior systemic anticancer therapy administered in the incurable recurrent or metastatic setting. Systemic therapy which was completed more than 6 months prior to randomization, if given as part of multimodal treatment for locally advanced disease, is allowed.
Have measurable disease based on RECIST 1.1 as determined by the site and confirmed by BICR. As a guidance to the site investigators, tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Subject has adequate organ function defined by the following parameters (all specimens must be collected within 15 days prior to randomization):
Hematological: Absolute neutrophil count (ANC) ≥1500/μL, Platelets ≥100,000/μL; Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L;
Renal: Estimated glomerular filtration rate ≥30 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
Hepatic: Total bilirubin ≤1.5 × ULN or direct bilirubin ≤ULN for subjects with total bilirubin levels >1.5 × ULN, Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5 ULN (if approved by Medical Monitor, ≤5 × ULN for subjects with liver metastases; AST and ALT >5 to 20 x ULN may be included if asymptomatic).
Coagulation: INR, prothrombin time (PT) ≤1.5 × ULN; if subject is receiving anticoagulant therapy, INR or PT- should be within therapeutic range of anticoagulant.
For female subjects defined as women of childbearing potential (WOCBP), a negative pregnancy test must be obtained during screening. If a urine test cannot be confirmed as negative, a serum pregnancy test will be required. Women who are surgically sterile or at least 2 years postmenopausal do not require pregnancy testing.
Male subjects of childbearing potential must agree to use a condom as an effective method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

You may not qualify if…

Primary tumor location of nasopharynx (any histology).
If the pregnancy test is positive. If a urine test cannot be confirmed as negative, a serum pregnancy test will be required.
Has received prior therapy with HPV-specific immunotherapy including therapeutic cancer vaccines and cellular immunotherapy. Note: subjects who have received prophylactic HPV vaccines are eligible for enrollment.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD- L2 agent or with an agent directed to another stimulatory or co- inhibitory T cell receptor including but not limited to CTLA-4, OX40, CD137.
Has had major surgery, including surgical resection of tumor, within 30 days prior to randomization, and has not fully recovered as assessed by the investigator.
Has received radiotherapy prior to randomization outside of the following minimum washout periods, and has not fully recovered as assessed by the investigator:
Fractionated radiotherapy, 2 weeks
Stereotactic radiosurgery, 1 week
Palliative radiation therapy, 1 week
Has received a live vaccine within 30 days prior to randomization.
Examples of live vaccines include, but are not limited to, the following:
measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist ® ) or live attenuated vaccines are not allowed within 30 days prior to randomization.
Has received immunomodulatory or immunosuppressive agents (e.g., interferons (IFNs), tumor necrosis factor, interleukins, immunoglobulins or other biological response modifiers (granulocyte colony-stimulating factor [GCSF] or granulocyte macrophage stimulating factor [GMCSF]) within 30 days prior to randomization.
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 30 days prior to randomization. Note: Subjects who entered the follow-up phase of an investigational study may participate as long as it is permitted in that study consent and has been 30 days after the last dose of the previous investigational agent.
Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. Note: Subjects who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of graft- versus-host disease [GVHD].
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (I a dose exceeding 10 mg daily of prednisone equivalent). Note: Current or recent use of intranasal, intra-articular, and topical steroids are allowed for symptom management are clinically indicated.
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ, superficial [non- infiltrated] bladder tumors) or other malignant tumors that have undergone potentially curative therapy are eligible for enrollment.
Has known carcinomatous meningitis and/or active central nervous system (CNS) metastases as defined by new brain metastases or progressive brain metastases that have not been subjected to CNS-directed therapy since documented progression. Note: Subjects with previously treated brain metastases are eligible if all the following criteria are met:
radiologically stable, i.e., without evidence of progression for at least 30 days by repeat imaging (note that repeat imaging should be performed during study screening),
neurologically stable, and
without requirement of steroid treatment for at least 14 days prior to randomization.
Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment and is allowed.
Has a history of interstitial lung disease or has current pneumonitis. Note: Subjects with a history of radiation pneumonitis who are fully recovered are eligible.
Has an active infection requiring systemic therapy (e.g., IV or oral anti-infective).
Has known human immunodeficiency virus (HIV) and CD4 count < 350 cells/μL and/or a history of an AIDS-defining opportunistic infection within the past 12 months. Note: Subjects who are on stable antiretroviral therapy for at least 30 days and have an HIV viral load less than 400 copies/mL and who do not meet the above exclusion criterion may be enrolled.

Where it is running

Mayo Clinic Arizona — Phoenix, Arizona, United States
Marin Cancer Care — Greenbrae, California, United States
University of California, Orange — Orange, California, United States
Yale University — New Haven, Connecticut, United States
Mayo Clinic Florida — Jacksonville, Florida, United States
Florida Cancer Affiliates - Ocala Oncology — Ocala, Florida, United States
SCRI - Florida Cancer Specialists — Orlando, Florida, United States
Emory University - Winship Cancer Institute (WCI) — Atlanta, Georgia, United States
University of Kansas — Westwood, Kansas, United States
University of Kentucky — Lexington, Kentucky, United States
Norton Cancer Institute — Louisville, Kentucky, United States
University of Louisville — Louisville, Kentucky, United States
University of Maryland — Baltimore, Maryland, United States
University of Michigan — Ann Arbor, Michigan, United States
Karmanos Cancer Institute — Detroit, Michigan, United States
Mayo Clinic Rochester — Rochester, Minnesota, United States
University of North Carolina — Chapel Hill, North Carolina, United States
The Ohio State University- James Cancer Hospital — Columbus, Ohio, United States
Penn State Health — Hershey, Pennsylvania, United States
Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States
Medical University of South Carolina — Charleston, South Carolina, United States
University of Tennessee Medical Center — Knoxville, Tennessee, United States
Texas Oncology — Austin, Texas, United States
UT Health San Antonio — San Antonio, Texas, United States
Texas Oncology-Northeast Texas — Tyler, Texas, United States

Full record on ClinicalTrials.gov

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