ACTIVE_NOT_RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 3 Open-Label, Randomized Study of PDS0101 and Pembrolizumab vs Pembrolizumab Alone in First-Line Treatment of Unresectable Recurrent and/or Metastatic HPV16+ Head and Neck Squamous Cell Carcinoma

Quick Facts

Study Start:2025-05-30

Study Completion:2029-02

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT06790966

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Subject (or legally acceptable representative, if applicable) provides written informed consent for the study. 2. Subject is ≥18 years of age on the day of signing the informed consent. 3. Have a history of histologically- or cytologically-confirmed diagnosis of recurrent and/or metastatic squamous cell cancer of the head and neck (HNSCC) with: 1. Eligible primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx. 2. HPV16 tumor positivity (central testing). 3. Tumor PD-L1 expression defined as a CPS ≥ 1 using the FDA- approved pembrolizumab (KEYTRUDA®) assay (local testing). 4. 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. 4. 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. 5. 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. 6. 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. 7. 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. 8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.	1. Primary tumor location of nasopharynx (any histology). 2. If the urine pregnancy test is positive. If the urine test cannot be confirmed as negative, a serum pregnancy test will be required. 3. 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. 4. 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. 5. 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. 6. 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 7. Has received a live vaccine within 30 days prior to randomization. 8. 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. 9. 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. 10. 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 \[GVHD\]. 11. 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. 12. 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. 13. 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: 1. 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), 2. neurologically stable, and 3. without requirement of steroid treatment for at least 14 days prior to randomization. 14. 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. 15. 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. 16. Has an active infection requiring systemic therapy (e.g., IV or oral anti-infective). 17. 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. 18. Has a history of hepatitis B (HBV) infection or known to be positive for HBV antigen (HbsAg)/HBV virus DNA. 19. Has active hepatitis C defined by a known positive C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay. Note: Subjects with a history of HCV infection who have completed curative antiviral treatment and have HCV viral load below the limit of quantification may be enrolled. 20. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 21. Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study. 22. Is breastfeeding within the projected duration of the study, starting with the screening visit through 120 days after the last dose of any study treatment. 23. Has had an allogenic tissue/solid organ transplant. 24. Female subjects defined as WOCBP unwilling or unable to use highly effective contraception method(s) for the duration of the study: 1. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation. 2. Progestogen-only hormonal contraception 3. Intrauterine device 4. Intrauterine hormone-releasing system 5. Bilateral tubal occlusion 6. Vasectomized partner is a highly effective birth control method provided that the partner is the sole sexual partner of the women of childbearing potential (WOCBP) trial participant and that the vasectomized partner has received medical assessment of surgical success. 25. History of allergic or hypersensitivity reactions (≥Grade 3) to pembrolizumab, PDS0101, or their excipients.

Inclusion Criteria

Exclusion Criteria

1. Subject (or legally acceptable representative, if applicable) provides written informed consent for the study.
2. Subject is ≥18 years of age on the day of signing the informed consent.
3. Have a history of histologically- or cytologically-confirmed diagnosis of recurrent and/or metastatic squamous cell cancer of the head and neck (HNSCC) with:
1. Eligible primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx.
2. HPV16 tumor positivity (central testing).
3. Tumor PD-L1 expression defined as a CPS ≥ 1 using the FDA- approved pembrolizumab (KEYTRUDA®) assay (local testing).
4. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

1. Primary tumor location of nasopharynx (any histology).
2. If the urine pregnancy test is positive. If the urine test cannot be confirmed as negative, a serum pregnancy test will be required.
3. 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.
4. 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.
5. 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.
6. 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
7. Has received a live vaccine within 30 days prior to randomization.
8. 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.
9. 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.
10. 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 \[GVHD\].
11. 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.
12. 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.
13. 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:
1. 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),
2. neurologically stable, and
3. without requirement of steroid treatment for at least 14 days prior to randomization.
14. 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.
15. 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.
16. Has an active infection requiring systemic therapy (e.g., IV or oral anti-infective).
17. 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.
18. Has a history of hepatitis B (HBV) infection or known to be positive for HBV antigen (HbsAg)/HBV virus DNA.
19. Has active hepatitis C defined by a known positive C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay. Note: Subjects with a history of HCV infection who have completed curative antiviral treatment and have HCV viral load below the limit of quantification may be enrolled.
20. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
21. Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study.
22. Is breastfeeding within the projected duration of the study, starting with the screening visit through 120 days after the last dose of any study treatment.
23. Has had an allogenic tissue/solid organ transplant.
24. Female subjects defined as WOCBP unwilling or unable to use highly effective contraception method(s) for the duration of the study:
1. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation.
2. Progestogen-only hormonal contraception
3. Intrauterine device
4. Intrauterine hormone-releasing system
5. Bilateral tubal occlusion
6. Vasectomized partner is a highly effective birth control method provided that the partner is the sole sexual partner of the women of childbearing potential (WOCBP) trial participant and that the vasectomized partner has received medical assessment of surgical success.
25. History of allergic or hypersensitivity reactions (≥Grade 3) to pembrolizumab, PDS0101, or their excipients.

Contacts and Locations

Principal Investigator

David Schaaf, MD

STUDY_DIRECTOR

PDS Biotechnology Corporation

Study Locations (Sites)

Mayo Clinic Arizona

Phoenix, Arizona, 85054

United States

Marin Cancer Care

Greenbrae, California, 94904

United States

University of California, Orange

Orange, California, 92686

United States

Yale University

New Haven, Connecticut, 06510

United States

Mayo Clinic Florida

Jacksonville, Florida, 32224

United States

Florida Cancer Affiliates - Ocala Oncology

Ocala, Florida, 34474

United States

SCRI - Florida Cancer Specialists

Orlando, Florida, 32827

United States

University of Kansas

Westwood, Kansas, 66205

United States

University of Kentucky

Lexington, Kentucky, 40536

United States

University of Louisville

Louisville, Kentucky, 40202

United States

University of Maryland

Baltimore, Maryland, 21201

United States

Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

Mayo Clinic Rochester

Rochester, Minnesota, 55905

United States

University of North Carolina

Chapel Hill, North Carolina, 27599-7025

United States

The Ohio State University- James Cancer Hospital

Columbus, Ohio, 43210

United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19103

United States

Medical University of South Carolina

Charleston, South Carolina, 29407

United States

University of Tennessee Medical Center

Knoxville, Tennessee, 37920

United States

Texas Oncology

Austin, Texas, 78705

United States

UT Health San Antonio

San Antonio, Texas, 78229

United States

Texas Oncology-Northeast Texas

Tyler, Texas, 75702

United States

University of Virginia Health System

Charlottesville, Virginia, 22903

United States

Virginia Oncology Associates

Norfolk, Virginia, 23502

United States

West Virginia University Cancer Center

Morgantown, West Virginia, 26506

United States

Collaborators and Investigators

Sponsor: PDS Biotechnology Corp.

David Schaaf, MD, STUDY_DIRECTOR, PDS Biotechnology Corporation

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-05-30

Study Completion Date2029-02

Study Record Updates

Study Start Date2025-05-30

Study Completion Date2029-02

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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

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

Conditions

Quick Navigation

Study Overview

Description

Official Title

Quick Facts

Study ID

Participation Criteria

Contacts and Locations

Principal Investigator

Study Locations (Sites)

Collaborators and Investigators

Study Record Dates

Study Registration Dates

Study Record Updates

Terms related to this study

Keywords Provided by Researchers

Additional Relevant MeSH Terms