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

NCT06790966 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: PDS0101-HNC-301
• Study Type: interventional
• Target: 351
• Locations: 1 country
• Sites: 28

Brief Summary

This is a global, multi-center, Phase 3 study that is randomized 2:1, 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.

Conditions

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

Keywords

Head and neck cancer; Head and neck neoplasms; Neoplasms, squamous cell; Squamous cell carcinoma of the head and neck; Head and neck squamous cell carcinoma; Recurrent Head and Neck cancer; Metastatic Head and Neck Cancer; Immuno-oncology therapy; Human papillomavirus-16; Cancer Vaccines; HNSCC; Oropharyngeal squamous cell carcinoma; HPV; Programmed cell death ligand 1; PD-L1; Immune checkpoint inhibitor; Immune checkpoint inhibitors; Immunotherapy; Squamous cell cancer; Pembrolizumab; Antineoplastic Agents, Immunological

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS is defined as the time from randomization until death from any cause.

  Up to 48 months

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Up to 27 months

• Disease Control Rate (DCR)

  Up to 27 months

• Duration of Response (DOR)

  Up to 27 months

• Progression-Free Survival (PFS)

  Up to 27 months

Other Outcomes (13)

• Safety

  Up to 48 months

• Progression-Free Survival 2 (PFS2)

  Up to 48 months

• European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L)

  Up to 48 months

Study Arms (2)

Interventional Arm

EXPERIMENTAL

PDS0101 + Pembrolizumab

Combination Product: Combination Treatment of PDS0101 and Pembrolizumab

Control Arm

ACTIVE COMPARATOR

Pembrolizumab

Drug: Pembrolizumab Monotherapy

Interventions

Pembrolizumab Monotherapy DRUG

Pembrolizumab (IV) every 3 weeks for up to 35 cycles.

Also known as: KEYTRUDA

Control Arm

Combination Treatment of PDS0101 and Pembrolizumab COMBINATION_PRODUCT

* Pembrolizumab (IV) every 3 weeks for up to 35 Cycles * PDS0101 (SC) during Cycles 1, 2, 3, 4, and 12

Also known as: Versamune HPV, KEYTRUDA

Interventional Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 urine pregnancy test must be obtained during screening. If the 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.

You may not qualify if:

• Primary tumor location of nasopharynx (any histology).
• If the urine pregnancy test is positive. If the 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 \[GVHD\].

Sponsors & Collaborators

• PDS Biotechnology Corp.: lead

Study Sites (28)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Marin Cancer Care

Greenbrae, California, 94904, United States

Location

University of California, Orange

Orange, California, 92686, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Florida Cancer Affiliates - Ocala Oncology

Ocala, Florida, 34474, United States

Location

SCRI - Florida Cancer Specialists

Orlando, Florida, 32827, United States

Location

Emory University - Winship Cancer Institute (WCI)

Atlanta, Georgia, 30322, United States

Location

University of Kansas

Westwood, Kansas, 66205, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599-7025, United States

Location

The Ohio State University- James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

Penn State Health

Hershey, Pennsylvania, 17033, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19103, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29407, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

Texas Oncology

Austin, Texas, 78705, United States

Location

UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

Texas Oncology-Northeast Texas

Tyler, Texas, 75702, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

West Virginia University Cancer Center

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma, Squamous Cell; Carcinoma

Study Officials

• David Schaaf, MD

  PDS Biotechnology Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase 3 open-label, active-control, 2:1 randomized study with parallel assignment of PDS0101 plus pembrolizumab (referred to as 'the investigational arm') vs pembrolizumab alone (referred to as 'the control arm')

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: January 24, 2025
• Study Start: May 30, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: December 11, 2025

Record last verified: 2025-12

Locations

US (28)