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Phase II Trial of Immunotherapeutic HPV Vaccine PRGN-2009 With Pembrolizumab Before Standard Treatment in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal Cancer

Primary Purpose

Oropharyngeal Squamous Cell Carcinoma (SCC)

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PRGN-2009
Pembrolizumab
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oropharyngeal Squamous Cell Carcinoma (SCC) focused on measuring HPV16/18, PD-1 inhibitor, Monoclonal Antibody

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA: Subjects must have cytologically or histologically confirmed newly diagnosed stage I (T1,2 N1), II or III p16-positive oropharyngeal squamous cell carcinoma (SCC) planned for definitive therapy (surgery or chemoradiotherapy). Subjects must have measurable disease, per RECIST 1.1. Age >=18 years. Eastern Cooperative Oncology Group [ECOG] performance status <= 2. Adequate hematologic function at screening, as follows: Absolute neutrophil count (ANC) >=1 x 10^9/L; Hemoglobin (Hgb) >= 9 g/dL; Platelets >= 75,000/microliter. Adequate renal and hepatic function at screening, as follows: Serum creatinine <= 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance >= 40 mL/min for participant with creatinine levels > 1.5 x ULN (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl); Total bilirubin <= 1.5 x ULN OR in subjects with Gilbert s syndrome, a total bilirubin <= 3.0 x ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x ULN, unless liver metastases are present, then values must be <= 3 x ULN. Participants serologically positive for HIV, Hepatitis B, or Hepatitis C are eligible if the viral loads are undetectable by quantitative PCR. Note: HIV positive participants must have CD4 count >= 200 cells/mm^3 at enrollment, be on stable antiretroviral therapy for at least 4 weeks and have no reported opportunistic infections or Castleman s disease within 12 months prior to enrollment. Women of child-bearing potential (WOCBP) must agree to use effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for at least 4 months following the last dose of pembrolizumab. Participants must be willing to undergo two research biopsies on this study. Ability of participant to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: Participants with prior investigational drug, live vaccine, chemotherapy, immunotherapy, or any prior radiotherapy (except for palliative bone directed therapy) within the past 4 weeks prior to the first drug administration. Participants may continue adjuvant hormonal therapy in the setting of a definitively treated cancer (e.g., breast). Major surgery within 28 days prior to the first drug administration (minimally invasive procedures such as diagnostic biopsies are permitted). Pregnant individuals as evaluated by a positive serum or urine Beta-hCG at screening Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent with the exception of: Diabetes type I, eczema, vitiligo, alopecia, psoriasis, hypo- or hyperthyroidism or other mild autoimmune disorders not requiring immunosuppressive treatment. Administration of glucocorticoids through a route known to result in a minimal systemic exposure (topical, intranasal, intraocular, or inhalation). Systemic (intravenous or oral) glucocorticoid (except for physiologic doses of corticosteroids, i.e., <= the equivalent of prednisone 10 mg/day) or other immunosuppressors such as azathioprine or cyclosporin A, are excluded because of potential immune suppression. These treatments must be discontinued at least 1 week prior to enrollment for recent short course use (<= 14 days). Glucocorticoids as premedication for contrast-enhanced studies is allowed prior to enrollment and on study. Participants with a prior or concurrent malignancy whose natural history or treatment that has potential to interfere with the safety or efficacy assessment of the regimen. Prior allogenic tissue/solid organ transplant. Participants with pulse oximetry < 92% on room air at screening. Uncontrolled intercurrent illness that would limit compliance with study requirements suggested by medical history, physical examination or standard clinical assessments such as imaging and laboratory studies.

Sites / Locations

  • National Institutes of Health Clinical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1

Arm Description

PRGN 5x10^11 Viral Particles (VP) SC plus pembrolizumab 200mg IV as induction/ neoadjuvant therapy

Outcomes

Primary Outcome Measures

Determine if there is an increase in CD3+ tumor infiltrating T cells post treatment compared with pre-treatment
CD3+ tumor infiltrating lymphocytes will be assessed by multiplex immunofluorescence from the surgical/ biopsy tissue collected at week 4-5 and compared with pre-treatment

Secondary Outcome Measures

Prolonged Survival
Assess if PRGN-2009 plus pembrolizumab results in significantly prolonged survival as compared to the expected 80% three-year historical survival in p16-positive OPC participants
Overall Survival
Assess OS and RFS once a year for 5 years
Safety
Incidence of treatment-related serious adverse events at baseline, W1, W3, on day 29, and 28 days after last treatment as defined by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Determine the rate of increase in TILs by immunohistologyCHANGE TO: Determine the rate of increase in tumor infiltrating lymphocytes (TILs) by immunohistology
Compare the induction of immune response of PRGN-2009 plus pembrolizumab with PRGN-2009 at completion visit compared with pre-treatment with endpoint the >=2-fold increase in tumor infiltrating lymphocytes

Full Information

First Posted
August 16, 2023
Last Updated
October 24, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05996523
Brief Title
Phase II Trial of Immunotherapeutic HPV Vaccine PRGN-2009 With Pembrolizumab Before Standard Treatment in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal Cancer
Official Title
Phase II Trial of Immunotherapeutic HPV Vaccine PRGN-2009 With Pembrolizumab Before Standard Treatment in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 13, 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 30, 2023 (Anticipated)
Primary Completion Date
November 1, 2024 (Anticipated)
Study Completion Date
November 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Background: Cancers in and around the mouth associated with human papilloma virus (HPV) are common. Two treatments (the drug pembrolizumab and the HPV vaccine PRGN-2009) have been shown to work well when used individually against these cancers. Researchers want to find out if they might work better when used together. Objective: To test pembrolizumab combined with PRGN-2009 in people with HPV-positive cancers in and around the mouth. Eligibility: Adults aged 18 and older newly diagnosed with HPV-positive cancers in and around the mouth. Design: Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans. They may need to have a biopsy: A sample of tissue will be taken from the tumor. PRGN-2009 is given as an injection under the skin. Pembrolizumab is given through a tube attached to a needle inserted into a vein in the arm. Participants will have at least 3 clinic visits: At the first, they will receive both the drug and the vaccine; 15 days later, they will receive a second shot of the vaccine. At the third visit, about 1 week after the second, they will have follow-up tests. During these visits, participants will give samples of blood, urine, and saliva. Imaging scans and biopsies will be repeated. They will have tests of their heart function. Participants may opt to return for another follow-up visit about 1 month after their second dose of the vaccine. Participants will have follow-up contacts by phone 3 and 6 months after starting the study. The calls will continue once a year for 5 years.
Detailed Description
Background -Human papilloma virus-associated oropharyngeal cancer (HPV-OPC) is the most common HPV-associated malignancy in the United States, with an increasing incidence. Although the prognosis for stage I HPV-OPC is favorable, about 20 percent of patients with stage II disease and 35 percent of patients with stage III disease will die within four years. The standard-of-care primary treatment for HPV-OPC without distant metastasis is definitive concurrent chemoradiotherapy (primarily) or surgery (which may be followed by adjuvant chemoradiotherapy). Neoadjuvant/induction immunotherapy is in clinical trials aiming to induce antigen-specific immunity prior to primary treatment and to reduce the risk of disease relapse. Pembrolizumab, an anti-PD-1 monoclonal antibody that is FDA-approved for first-line treatment of recurrent/metastatic head and neck squamous cell cancer (HNSCC) has been used in these trials and shown to be safe and active. PRGN-2009 is an anti-HPV immunotherapeutic vaccine. It has demonstrated induction of HPV antigen-specific responses and tumor growth inhibition in pre-clinical models of HPV-associated malignancy, with improved anti-tumor efficacy upon addition of T-cell immune checkpoint blockade. In a Phase I/II trial at the NCI it has demonstrated excellent safety and tolerability as monotherapy or in combination with checkpoint blockade in recurrent/metastatic disease but also as monotherapy in neoadjuvant/induction context for HPV-OPC. Objective: -To determine if the use of PRGN-2009 with pembrolizumab in participants with p16-positive OPC can result in a >= 2-fold increase in CD3+ tumor infiltrating T cells post treatment compared with pre-treatment. Eligibility: Age >= 18 years. Pathologically confirmed newly diagnosed Stage I (T1, T2; N1), II or III p16-positive OPC. Design: This is a Phase II study to evaluate the effect of PRGN-2009 and pembrolizumab before definitive treatment in subjects with p16-positive OPC. Participants will receive PRGN-2009 and pembrolizumab prior to definitive treatment. Participants will receive two doses of PRGN-2009 5x10^11 viral particles (VP) subcutaneously (SC) approximately two weeks apart, and one dose of pembrolizumab 200 mg intravenously (IV) concurrently with the first vaccine dose. Up to 20 evaluable participants will be enrolled.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oropharyngeal Squamous Cell Carcinoma (SCC)
Keywords
HPV16/18, PD-1 inhibitor, Monoclonal Antibody

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
PRGN 5x10^11 Viral Particles (VP) SC plus pembrolizumab 200mg IV as induction/ neoadjuvant therapy
Intervention Type
Biological
Intervention Name(s)
PRGN-2009
Intervention Description
PRGN-2009 5x10^11 viral particles (VP) subcutaneously (SC) approximately two weeks apart
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
Pembrolizumab 200 mg intravenously (IV) concurrently with the first vaccine dose
Primary Outcome Measure Information:
Title
Determine if there is an increase in CD3+ tumor infiltrating T cells post treatment compared with pre-treatment
Description
CD3+ tumor infiltrating lymphocytes will be assessed by multiplex immunofluorescence from the surgical/ biopsy tissue collected at week 4-5 and compared with pre-treatment
Time Frame
4-5 weeks
Secondary Outcome Measure Information:
Title
Prolonged Survival
Description
Assess if PRGN-2009 plus pembrolizumab results in significantly prolonged survival as compared to the expected 80% three-year historical survival in p16-positive OPC participants
Time Frame
3-6 months
Title
Overall Survival
Description
Assess OS and RFS once a year for 5 years
Time Frame
5 years
Title
Safety
Description
Incidence of treatment-related serious adverse events at baseline, W1, W3, on day 29, and 28 days after last treatment as defined by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time Frame
Up to 28 days after last treatment
Title
Determine the rate of increase in TILs by immunohistologyCHANGE TO: Determine the rate of increase in tumor infiltrating lymphocytes (TILs) by immunohistology
Description
Compare the induction of immune response of PRGN-2009 plus pembrolizumab with PRGN-2009 at completion visit compared with pre-treatment with endpoint the >=2-fold increase in tumor infiltrating lymphocytes
Time Frame
4 weeks CHANGE TO: 4-5 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: Subjects must have cytologically or histologically confirmed newly diagnosed stage I (T1,2 N1), II or III p16-positive oropharyngeal squamous cell carcinoma (SCC) planned for definitive therapy (surgery or chemoradiotherapy). Subjects must have measurable disease, per RECIST 1.1. Age >=18 years. Eastern Cooperative Oncology Group [ECOG] performance status <= 2. Adequate hematologic function at screening, as follows: Absolute neutrophil count (ANC) >=1 x 10^9/L; Hemoglobin (Hgb) >= 9 g/dL; Platelets >= 75,000/microliter. Adequate renal and hepatic function at screening, as follows: Serum creatinine <= 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance >= 40 mL/min for participant with creatinine levels > 1.5 x ULN (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl); Total bilirubin <= 1.5 x ULN OR in subjects with Gilbert s syndrome, a total bilirubin <= 3.0 x ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x ULN, unless liver metastases are present, then values must be <= 3 x ULN. Participants serologically positive for HIV, Hepatitis B, or Hepatitis C are eligible if the viral loads are undetectable by quantitative PCR. Note: HIV positive participants must have CD4 count >= 200 cells/mm^3 at enrollment, be on stable antiretroviral therapy for at least 4 weeks and have no reported opportunistic infections or Castleman s disease within 12 months prior to enrollment. Women of child-bearing potential (WOCBP) must agree to use effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for at least 4 months following the last dose of pembrolizumab. Participants must be willing to undergo two research biopsies on this study. Ability of participant to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: Participants with prior investigational drug, live vaccine, chemotherapy, immunotherapy, or any prior radiotherapy (except for palliative bone directed therapy) within the past 4 weeks prior to the first drug administration. Participants may continue adjuvant hormonal therapy in the setting of a definitively treated cancer (e.g., breast). Major surgery within 28 days prior to the first drug administration (minimally invasive procedures such as diagnostic biopsies are permitted). Pregnant individuals as evaluated by a positive serum or urine Beta-hCG at screening Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent with the exception of: Diabetes type I, eczema, vitiligo, alopecia, psoriasis, hypo- or hyperthyroidism or other mild autoimmune disorders not requiring immunosuppressive treatment. Administration of glucocorticoids through a route known to result in a minimal systemic exposure (topical, intranasal, intraocular, or inhalation). Systemic (intravenous or oral) glucocorticoid (except for physiologic doses of corticosteroids, i.e., <= the equivalent of prednisone 10 mg/day) or other immunosuppressors such as azathioprine or cyclosporin A, are excluded because of potential immune suppression. These treatments must be discontinued at least 1 week prior to enrollment for recent short course use (<= 14 days). Glucocorticoids as premedication for contrast-enhanced studies is allowed prior to enrollment and on study. Participants with a prior or concurrent malignancy whose natural history or treatment that has potential to interfere with the safety or efficacy assessment of the regimen. Prior allogenic tissue/solid organ transplant. Participants with pulse oximetry < 92% on room air at screening. Uncontrolled intercurrent illness that would limit compliance with study requirements suggested by medical history, physical examination or standard clinical assessments such as imaging and laboratory studies.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marissa B Mallek, R.N.
Phone
(240) 760-7498
Email
marissa.mallek@nih.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Charalampos Floudas, M.D.
Phone
(240) 858-3032
Email
charalampos.floudas@nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charalampos Floudas, M.D.
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
National Cancer Institute Referral Office
Phone
888-624-1937
Email
ncimo_referrals@mail.nih.gov

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
.All collected IPD will be shared.@@@@@@All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.@@@@@@
IPD Sharing Time Frame
Data from this study may be requested from other researchers no sooner than 3 years after the completion of the primary endpoint.@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active@@@@@@@@@@@@
IPD Sharing Access Criteria
Data from this study may be requested by contacting the PI@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.@@@@@@
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_001536-C.html
Description
NIH Clinical Center Detailed Web Page

Learn more about this trial

Phase II Trial of Immunotherapeutic HPV Vaccine PRGN-2009 With Pembrolizumab Before Standard Treatment in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal Cancer

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