Clinical Trials /

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



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).

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:



Phase 2

Trial Eligibility



  • Brief Title: Study of PDS0101 and Pembrolizumab Combination I/O in Subjects With HPV16 + Recurrent and/or Metastatic HNSCC
  • 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

Clinical Trial IDs

  • ORG STUDY ID: PDS0101-HNC-201
  • NCT ID: NCT04260126


  • 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


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).

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.

Trial Arms

Pembrolizumab and PDS0101ExperimentalPembrolizumab 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.

    Eligibility Criteria

            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
                   -  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
                   -  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
              -  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
              -  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
              -  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
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Objective Response Rate (ORR) of the combination of Pembrolizumab and PDS0101
    Time Frame:9 months following initial treatment
    Safety Issue:
    Description:RECIST 1.1

    Secondary Outcome Measures

    Measure:Progression-Free Survival (PFS) in all patients
    Time Frame:12 and 24 months
    Safety Issue:
    Description:RECIST 1.1
    Measure:Overall Survival in all patients
    Time Frame:24 months
    Safety Issue:
    Description: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.
    Measure: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
    Safety Issue:
    Description:AE's will be summarized by severity using NCI CTCAE, version 50 (v.11.27.17) and by relationship to study treatment.


    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:PDS Biotechnology Corp.

    Trial Keywords

    • Head and Neck Squamous Cell Carcinoma
    • Human Papillomavirus
    • Immunotherapy
    • PDS0101
    • Vaccine
    • Human papillomavirus 16
    • Keynote 643
    • MK3475-643

    Last Updated

    July 12, 2021