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A Vaccine (PDS0101) Alone or in Combination With Pembrolizumab for the Treatment of Locally Advanced Human Papillomavirus-Associated Oropharynx Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05232851
Recruitment Status : Recruiting
First Posted : February 10, 2022
Last Update Posted : March 14, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:
This phase I/II trial studies how well PDS0101 alone or in combination with pembrolizumab works to shrink tumor in patients with human papillomavirus-associated oropharynx cancer that has spread to nearby tissue or lymph nodes (locally advanced). PDS0101 is a vaccine made from specific peptides that may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving PDS0101 with or without pembrolizumab may kill more tumor cells in patients with locally advanced human papillomavirus-associated oropharynx cancer before surgery so that it may make the tumor smaller and may reduce the amount of normal tissue that needs to be removed.

Condition or disease Intervention/treatment Phase
Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Human Papillomavirus-Related Carcinoma Locally Advanced Oropharyngeal Carcinoma Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8 Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8 Biological: Liposomal HPV-16 E6/E7 Multipeptide Vaccine PDS0101 Biological: Pembrolizumab Phase 1 Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

I. To determine pathologic and human papillomavirus cell-free tumor deoxyribonucleic acid (ctHPVDNA) response to liposomal HPV-16 E6/E7 multipeptide vaccine PDS0101 (PDS0101) or PDS0101 plus pembrolizumab in patients with high risk human papillomavirus-associated oropharynx cancer (HPV-OPSCC).

SECONDARY OBJECTIVES:

I. To determine tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

II. To determine progression-free survival and overall survival.

TERTIARY OBJECTIVES:

I. To determine the safety of PDS0101 delivered alone or with pembrolizumab.

CORRELATIVE RESEARCH OBJECTIVES:

I. Determine the changes in tumor microenvironment (TME) with PDS0101 alone or with pembrolizumab.

II. Determine circulating ctHPVDNA as a biomarker for tumor response. III. Determine HPV16-specific T-cell response utilizing multiplex flow cytometry and other parameters.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive liposomal HPV-16 E6/E7 multipeptide vaccine PDS0101 (PDS0101) subcutaneously (SC) on day 1. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive PDS0101 SC on day 1 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for up to 2 years.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Stimulating Immune Response With Neoadjuvant Human Papilloma Virus (HPV)-16 Specific Vaccination in HPV-Oropharyngeal Squamous Cell Carcinoma (HPV-OPSCC)
Actual Study Start Date : March 7, 2022
Estimated Primary Completion Date : July 1, 2023
Estimated Study Completion Date : July 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines

Arm Intervention/treatment
Experimental: Arm A (PDS0101)
Patients receive PDS0101 SC on day 1. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
Biological: Liposomal HPV-16 E6/E7 Multipeptide Vaccine PDS0101
Given SC
Other Names:
  • mmunoMAPK-RDOTAP /HPV-16 E6/E7 Peptide Antigen Vaccine
  • PDS0101

Experimental: Arm B (PDS0101, pembrolizumab)
Patients receive PDS0101 SC on day 1 and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
Biological: Liposomal HPV-16 E6/E7 Multipeptide Vaccine PDS0101
Given SC
Other Names:
  • mmunoMAPK-RDOTAP /HPV-16 E6/E7 Peptide Antigen Vaccine
  • PDS0101

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475




Primary Outcome Measures :
  1. Proportion of pathologic and human papillomavirus cell-free tumor deoxyribonucleic acid (ctHPVDNA) response [ Time Frame: Up to 2 years ]
    Will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the exact binomial method for each arm separately.


Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Time from registration to the first of either disease progression or death from any cause, assessed up to 2 years ]
    Patients who receive the study drug, but then never return for an evaluation will be censored on their last follow-up date. PFS will be estimated using the method of Kaplan-Meier. PFS rates at 12 and 24 months will also be reported.

  2. Overall survival (OS) [ Time Frame: Time from registration to death from any cause, assessed up to 2 years ]
    OS will be estimated using the method of Kaplan Meier.

  3. Response rate [ Time Frame: Up to 2 years ]
    Will be estimated using Response Evaluation Criteria in Solid Tumors 1.1 criteria. A tumor response is defined to be either a complete response or partial response noted up until surgery. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response. Patients who go off study early before having a tumor assessment performed will be considered a failure.

  4. Incidence of adverse events (AEs) [ Time Frame: Up to 30 days after treatment discontinuation ]
    All patients that have initiated treatment will be considered evaluable for AE analyses. The maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine AE patterns. AEs will be analyzed separately by arm.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >= 18 years
  • Disease characteristics

    • Locally advanced HPV-OPSCC and high-risk HPV-specific testing with at least one of the following:

      • Radiology extranodal extension (ENE) OR
      • cN2 (AJCC 8th Edition) disease (contralateral/bilateral nodes) OR
      • cN3(AJCC 8th Edition) disease (lymph node [LN] > 6 cm) OR
      • Radiographic evidence of 4 or more involved lymph nodes
    • Candidate for surgical resection
  • Measurable or unmeasurable disease as defined by RECIST 1.1 criteria
  • Eastern Cooperative Oncoloogy Group (ECOG) performance status of 0 or 1
  • White blood cell (WBC) count >= 3,000/mm^3 (=< 15 days prior to registration)
  • Platelet count >= 75,000/mm^3 (=< 15 days prior to registration)
  • Hemoglobin >= 9.0 g/dL (5.6 mmol/L) (=< 15 days prior to registration)

    • NOTE: Transfusions are not allowed =< 7 days prior to registration
  • Total bilirubin =< 1.5 X upper limit of normal (ULN) (or total bilirubin =< 3.0 X ULN with direct bilirubin =<1.5 X ULN in patients with well-documented Gilbert's Syndrome) (=< 15 days prior to registration)
  • Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT) =< 2.5 X ULN (=< 15 days prior to registration)
  • Creatinine =< 1.5 mg/dL (133 umol/L) OR calculated creatinine clearance >= 30 mL/min/1.73m^2 for patients with creatinine levels above ULN (=< 15 days prior to registration)
  • Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) =< 1.5 X ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of anticoagulants (=< 15 days prior to registration)
  • Negative pregnancy test done =< 3 days prior to registrationfor persons of childbearing potential only
  • Persons of childbearing potential or able to father a child must be willing to use an effective method of contraceptionfor the course of the study starting with the first dose of study therapy through 120 days after the last dose of study medication

    • NOTE: Abstinence is acceptable if this is the usual lifestyle and preferred method of contraception for the patient
  • Provide written informed consent
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
  • Willingness to provide mandatory blood specimens for correlative research
  • Willingness to provide mandatory tissue specimens for correlative research
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

Exclusion Criteria:

  • Active autoimmune disease requiring systemic treatment, documented history of severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents

    • NOTE: Exceptions are allowed for:

      • Vitiligo
      • Resolved childhood asthma/atopy
      • Intermittent use of bronchodilators or inhaled steroids
      • Daily steroids at dose of =< 10mg of prednisone (or equivalent)
      • Local steroid injections
      • Stable hypothyroidism on replacement therapy
      • Stable diabetes mellitus
      • Sjogren's syndrome
  • Any prior head or neck chemotherapy, radiotherapy, and/or immunotherapy
  • Any of the following prior therapies:

    • Live vaccine < 30 days prior to registration, including intranasal flu vaccine (e.g. Flu-Mist) (Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed). Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist) are live attenuated vaccines and are not allowed
    • Chemotherapy or targeted small molecule therapy < 21 days prior to registration
    • Investigational therapy or investigational device < 30 days prior to registration
    • Any prior investigational HPV-specific therapeutic vaccine
  • Current or prior use of immunosuppressive medication < 14 days prior to registration

    • The following are exceptions to this criterion:

      • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intraarticular injection)
      • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
      • Steroids as premedication for hypersensitivity reactions (e.g., premedication for computed tomography [CT] scans)
  • Uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection requiring systemic therapy
    • Interstitial lung disease
    • Serious, chronic gastrointestinal conditions associated with diarrhea (e.g., Crohn's disease or others)
    • Known active hepatitis B (i.e., known positive HBV surface antigen (HBsAg) reactive)
    • Known active hepatitis C (i.e., positive for HCV ribonucleic acid [RNA] detected by polymerase chain reaction [PCR])
    • Known human immunodeficiency virus (HIV) (Note: Patients on stable highly active antiretroviral therapy (HAART) for >= 6 weeks with CD4 counts >= 200 cells/mm^3 undetectable HIV viral load by quantitative PCR and no opportunistic infections Castlemaan's Disease =< 12 months prior to enrollment are allowed)
    • Known active tuberculosis (TB)
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Unstable cardiac arrhythmia or
    • Psychiatric illness/social situations that would limit compliance with study requirements (e.g., substance abuse)
  • History of allogeneic hematopoietic transplant or any solid organ transplant
  • Other active malignancy < 2 years prior to registration

    • EXCEPTIONS: Non-melanotic skin cancer (SCC/BCC), micropapillary thyroid cancer, Gleason 6 prostate cancer, carcinoma-in-situ of the breast or cervix
  • Any of the following conditions =< 6 weeks prior to registration:

    • Cerebrovascular accident (CVA)
    • Admission for unstable angina
    • Cardiac angioplasty or stenting or coronary artery bypass graft surgery
    • Untreated pulmonary embolism or untreated deep venous thrombosis (DVT)
    • Arterial thrombosis
  • Receipt of immunotherapy/immunomodulatory or immunosuppressive agents (e.g., IFNs, tumor necrosis factor, interleukins, immunoglobulins or other biologic response modifiers [GM-CSF, GCSF] =< 6 weeks prior to registration

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05232851


Locations
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United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015    mayocliniccancerstudies@mayo.edu   
Principal Investigator: David M. Routman, M.D.         
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
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Principal Investigator: David M Routman Mayo Clinic in Rochester
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Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT05232851    
Other Study ID Numbers: MC200710
NCI-2022-00497 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC200710 ( Other Identifier: Mayo Clinic in Rochester )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: February 10, 2022    Key Record Dates
Last Update Posted: March 14, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Oropharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Pembrolizumab
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents