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Study of PDS0101 and Pembrolizumab Combination I/O in Subjects With HPV16 + Recurrent and/or Metastatic HNSCC (VERSATILE002)

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. Identifier: NCT04260126
Recruitment Status : Recruiting
First Posted : February 7, 2020
Last Update Posted : February 3, 2021
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
PDS Biotechnology Corp.

Brief Summary:
VERSATILE-002 is a Phase 2, open-label, multicenter study of the efficacy and safety of PDS0101 administered in combination with pembrolizumab in the first line treatment of adults with HPV16 and PD-L1 positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Condition or disease Intervention/treatment Phase
Metastatic Head and Neck Cancer Recurrent Head and Neck Cancer HPV Positive Oropharyngeal Squamous Cell Carcinoma HPV-Related Esophageal Squamous Cell Carcinoma Neoplasms, Head and Neck Combination Product: Pembrolizumab and PDS0101 Phase 2

Detailed Description:
PDS0101 is a novel T-cell immunotherapy delivered subcutaneously that has been shown to stimulate high levels of HPV16-specific CD8+ and CD4+ T cells within patients by activating multiple immune pathways. These HPV-specific T cells then target tumors such as head and neck, anal and cervical cancers that are caused by HPV infection. The number of HNSCC cases has been increasing steadily over the last 10-15 years and over 90% of HPV-positive head and neck cancers are HPV16 positive. Pembrolizumab has been shown to have efficacy against both HPV-positive and HPV-negative head and neck cancers. However, its effectiveness is more optimal in tumors that are PD-L1 positive and have evidence of immune cells within the tumor. We hypothesize that increasing tumor-targeting HPV-specific T-cells with PDS0101 will be associated with an increased response to pembrolizumab. This study will explore in a preliminary manner whether combination treatment with PDS0101 plus pembrolizumab will improve clinical efficacy over that seen with pembrolizumab alone in the KEYNOTE-048 study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open-Label, Multi-Center Study of PDS0101 and Pembrolizumab (KEYTRUDA®) Combination Immunotherapy as a First Line Treatment in Subjects With Recurrent and/or Metastatic HNSCC and High-Risk HPV16 Infection
Estimated Study Start Date : February 5, 2021
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Pembrolizumab and PDS0101
Pembrolizumab will be administered via IV Infusion followed by subcutaneous injections of PDS0101 five times throughout the course of the study. Pembrolizumab monotherapy will be administered every cycle there is not a combination treatment until disease progression or up to Cycle 35.
Combination Product: Pembrolizumab and PDS0101
IV infusion of pembrolizumab 200 mg + two 0.5mL sub-cutaneous injections of PDS0101 administered on Cycle 1, 2, 3, 4 and 12. IV infusion of Pembrolizumab 200 mg monotherapy will be administered Cycles 5 - 11 and 13 - 35.

Primary Outcome Measures :
  1. Objective Response Rate (ORR) of the combination of Pembrolizumab and PDS0101 [ Time Frame: 9 months following initial treatment ]
    RECIST 1.1

Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) in all patients [ Time Frame: 12 and 24 months ]
    RECIST 1.1

  2. Overall Survival in all patients [ Time Frame: 24 months ]
    Overall survival (OS) is defined as time from date of first dose until death from any cause. Those subjects who are still alive will be censored at their last known date of contact.

  3. Incidence of Treatment-Emergent Adverse Events using NCI CTCAE, version 50 (v.11.27.17) [Safety and Tolerability] of Pembrolizumab and PDS0101 combination treatment [ Time Frame: 24 months ]
    AE's will be summarized by severity using NCI CTCAE, version 50 (v.11.27.17) and by relationship to study treatment.

Other Outcome Measures:
  1. Duration of response for all patients [ Time Frame: Up to 35 months ]
    Length of time that the subjects who demonstrated ORR at 9 months, continue to respond to treatment.

  2. Evaluate anti-HPV-16 E6 and E7 immune responses elicited by treatment with pembrolizumab and PDS0101 [ Time Frame: Baseline (Cycle 1) to Day 253 (Cycle 13) ]
    Using Granzyme B and interferon-γ (IFN-γ) ELISPOT immunoassays to compare pre-treatment baseline with Days 85 (Cycle 5) and 253 (Cycle 13).

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

Inclusion Criteria:

  • The participant (or legally acceptable representative if applicable) provides written informed consent for the study.
  • Be ≥18 years of age on the day of signing the informed consent.
  • Have a history of histologically or cytologically- confirmed diagnosis of squamous cell cancer of the head and neck (HNSCC) that is recurrent, metastatic, or persistent with:

    • Confirmed HPV16 infection
    • Confirmed tumor PDL1 expression defined as a CPS ≥1 using the FDA-approved Dako PD-L1 IHC 22C3 PharmDx Assay.
  • Subjects may not have received any immunological therapy for metastatic disease.
  • Have recurrent and/or metastatic measurable disease based on RECIST 1.1 as assessed by the local PI/radiology. There must be confirmation that the subject's imaging shows at least 1 lesion that is appropriate for selection as a target lesion per RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Have adequate organ function as defined below. Specimens must be collected within 10 days prior to the start of study combination treatment.

    • Absolute neutrophil count (ANC) > 1500 /uL
    • Absolute lymphocyte count (ALC) > 500/uL
    • Platelets > 100,000/uL
    • Hemoglobin > 9.0 g/dL
    • Creatine OR measured or calculated creatinine clearance < 1.5 x ULN OR > 30 ml/min for participants with creatinine levels >1.5 X institutional ULN
    • Total bilirubin < 1.5 ULN OR direct bilirubin < ULN for subjects with total bilirubin levels > 1.5 x ULN
    • AST (SGOT) AND ALT (SGPT) < 2.5 x ULN (< 5 x ULN for subjects with liver metastases)
    • International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT) < 1.5 x ULN unless participant is receiving anticoagulant therapy and PT or aPTT is within therapeutic range of intended use of anticoagulants.
  • If subject received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
  • For female subjects defined as Women of childbearing potential (WOCBP) a negative serum pregnancy test (β-human chorionic gonadotropin) must be obtained within 14 days prior to Day 1. 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 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.

Exclusion Criteria:

  • Pregnancy Exclusion: A female subject defined as a WOCBP who has a positive serum pregnancy test (e.g. within 14 days) prior to treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD- L1, or anti-PD-L2 agent with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX40, CD137) and was discontinued from that treatment due to a Grade 3 or higher AE.
  • Has received prior systemic anti-cancer therapy including investigational agents within 30 days prior to treatment.

Note: Subjects must have recovered from all AEs due to previous therapies to <Grade 1 or baseline. Subjects with <Grade 2 neuropathy and <Grade 2 alopecia are an exception to this criterion and may qualify for therapy.

Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting treatment.

  • Has received prior radiotherapy within 2 weeks of start of study treatment. Subjects must have recovered from all-radiation-related toxicities, not require corticosteroids and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (<2 weeks of radiotherapy) to non- CNS disease.
  • Has received a live vaccine within 30 days prior to the first dose of treatment. 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 (e.g. FluMist®) are live attenuated vaccines and are not allowed.
  • Received immunotherapy/immunomodulatory or immunosuppressive agents (e.g. IFNs, tumor necrosis factor, interleukins, immunoglobulins or other biological response modifiers [GM-CSF, granulocyte colony-stimulating factor, macrophage colony- stimulating factor]) within 6 weeks prior to administration of the first study combination treatment.
  • 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 the first dose of study treatment.

Note: Subjects who entered the follow-up phase of an investigational study may participate as long as it 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. (Subjects 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 (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Current or recent use of physiologic doses of intra-articular, topical, or inhaled corticosteroids is acceptable.
  • 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) that have undergone potentially curative therapy are not excluded.

  • Has known active central nervous system (CNS) metastases and/or carcinomatosis meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that repeat imaging should be performed during study screening clinical stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment).
  • Has severe hypersensitivity (>Grade 3) to pembrolizumab and/or any of its excipients.
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not consider a form of systemic treatment and is allowed.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Subjects with known HIV and/or history of Hepatitis B or C infections or known to be positive for Hepatitis B antigen (HBsAg)/Hepatitis B virus (HBV) DNA or Hepatitis C Antibody or RNA. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator.
  • Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of any study treatment.
  • Has had an allogenic tissue/solid organ transplant.
  • Has had a prior anti-cancer monoclonal antibody(mAb) within 30 days prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at baseline) from adverse events due to agents administered more than 30 days earlier.
  • Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GMCSF or recombinant erythropoietin) within 30 days prior to study Day 1.
  • Has a history of interstitial lung disease.
  • Female subjects defined as WOCBP unwilling or unable to use highly effective contraception method(s) for the duration of the study:

    • Combined hormonal contraception
    • Progestogen-only hormonal contraception
    • Intrauterine device
    • Intrauterine hormone-releasing system
    • Bilateral tubal occlusion
    • Vasectomized partner

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 identifier (NCT number): NCT04260126

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Contact: Misha Binder (732) 766-0074
Contact: Cara Lalley (908) 472-6979

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United States, Kentucky
University of Kentucky Chandler Medical Center - Markey Cancer Center Recruiting
Lexington, Kentucky, United States, 40536
Contact: Whitney Michels   
Principal Investigator: Alexandra Kejner, MD         
Norton Cancer Institute Recruiting
Louisville, Kentucky, United States, 40241
Contact: Jaspreet Grewal, MD       Head&   
Principal Investigator: Jaspreet Grewal, MD         
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Ammar Sukari, MD    800-527-6266      
Principal Investigator: Ammar Sukari, MD         
United States, Tennessee
University of Tennessee Recruiting
Knoxville, Tennessee, United States, 37920
Contact: Brenna Adelman    865-305-5131   
Principal Investigator: Timothy Panella, MD         
Sponsors and Collaborators
PDS Biotechnology Corp.
Merck Sharp & Dohme Corp.
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Study Director: Lauren Wood, MD PDS Biotechnology Corporation
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Responsible Party: PDS Biotechnology Corp. Identifier: NCT04260126    
Other Study ID Numbers: PDS0101-HNC-201
First Posted: February 7, 2020    Key Record Dates
Last Update Posted: February 3, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by PDS Biotechnology Corp.:
Head and Neck Squamous Cell Carcinoma
Human Papillomavirus
Human papillomavirus 16
Keynote 643
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Head and Neck Neoplasms
Esophageal Squamous Cell Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplasms by Site
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents