A Study to Evaluate PDS0101 and Pembrolizumab Combination to Treat Subjects with HPV16 + Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma


NCT ID: NCT04260126
Sponsor Protocol Number: PDS0101-HNC-201

About this study

The purpose of this study is to evaluate the effectiveness 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).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • The subject (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.
  • Checkpoint-naïve subjects: Have a history of histologically- 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 combined positive score (CPS) ≥ 1 using the FDA- approved Dako PD-L1 IHC 22C3 PharmDx Assay;
    • No prior receipt of any immunological therapy for metastatic disease.
  • Checkpoint experienced subjects have a history of histologically-confirmed diagnosis of HNSCC that is recurrent, metastatic, or persistent with:
    • Confirmed HPV16 infection;
    • Characterization of tumor PDL1 expression using the FDA-approved PD-L1 IHC 22C3 PharmDx Assay;
    • Receipt of prior treatment with checkpoint inhibitors as a single agent or in combination, and have received at least 2 doses of the agent or a minimum of 6 weeks on treatment;
    • Have documented clinical progression or recurrence that has been radiologically confirmed.
  • 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.
  • Llesion 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 in:
  • Hematological:
    • ANC ≥ 1500/µL;
    • Platelets ≥100 000/µL; Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L;
  • Renal:
    • ​​​​​​​Creatinine ≤ 1.5 × ULN or >1.5 × institutional ULN;
  • Hepatic:
    • ​​​​​​​Total bilirubin ≤ 1.5 × ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 × ULN;
    • AST and ALT ≤ 2.5 ULN (5 × ULN for subjects with liver metastases);
  • Coagulation:
    • ​​​​​​​INR, PT or PTT 1.5 × ULN. S
    • Specimens must be collected within 10 days prior to the start of study combination treatment.
  • 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 urine pregnancy test must be obtained during screening. Women who are surgically sterile or at least 2 years postmenopausal do not require pregnancy testing.​​​​​​​
    • Note: Female subjects of childbearing potential must be willing to use an effective method of contraception for the course of the study through 120 days after the last dose of study medication.
  • 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:

Subjects are excluded from study if any of the following criteria apply:

  • A female subject defined as a WOCBP who has a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • 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 (eg, CTLA-4, OX40, CD137) and was discontinued from that treatment due to a Grade 3 or higher adverse events (AE).
  • Has received prior systemic anticancer therapy including investigational agents within 30 days prior to treatment. Note: Subjects must have recovered from all AEs due to previous therapies to
  • < Grade 2 neuropathy and < Grade 2 alopecia are an exception to this criterion and may qualify for therapy.
    • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting treatment.
  • Coordination and timing of COVID-19 vaccination should be based on local Investigator clinical assessment and judgment.
    • Note: Whenever possible, it is recommended to avoid COVID vaccination on the day of PDS0101 and/or pembrolizumab dosing because it may be difficult to attribute certain AEs (e.g., fever, infusion reaction) to the study drug(s) or the COVID vaccine if they are both administered on the same day.
  • 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 (eg, FluMist®) are live attenuated vaccines and are not allowed.
  • Received immunotherapy/immunomodulatory or immunosuppressive agents (eg, 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 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]).
  • 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 immuno-suppressive 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) or other malignant tumors 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, ie, 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 hepatitis 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 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.
  • 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 received administration of colony-stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 30 days prior to 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.
  • Any prior Grade ≥ 3 immune-related adverse event (irAE) while receiving any previous checkpoint inhibitor or immunotherapy agent, or any unresolved irAE > Grade 1 except for endocrine AEs managed with replacement therapy.
  • Developed immune-related toxicity while on prior checkpoint inhibitor therapy that has not yet returned to
  • Grade 1 or better.

Eligibility last updated 9/1/21. Questions regarding updates should be directed to the study team contact.


More information


  • Certain types of cationic lipids have shown promise in cancer immunotherapy, but their mechanism of action is poorly understood. In this study, we describe the properties of an immunotherapeutic consisting of the pure cationic lipid enantiomer R-1,2-dioleoyl-3-trimethyl-ammonium-propane (R-DOTAP) formulated with modified viral or self-peptide Ags. R-DOTAP formulations with peptide Ags stimulate strong cross-presentation and potent CD8 T cell responses associated with a high frequency of polyfunctional CD8 T cells. In a human papillomavirus tumor model system, a single s.c. injection of tumor-bearing mice with R-DOTAP plus human papillomavirus Ags induces complete regression of large tumors associated with an influx of Ag-specific CD8 T cells and a reduction of the ratio of regulatory/Ag-specific CD8 T cells. R-DOTAP also synergizes with an anti-PD1 checkpoint inhibitor, resulting in a significant inhibition of B16 melanoma tumor growth. We found that R-DOTAP stimulates type I IFN production by dendritic cells in vivo and in vitro. s.c. injection of R-DOTAP results in an IFN-dependent increase in draining lymph node size and a concomitant increase in CD69 expression. Using knockout mice, we show that type I IFN is required for the induction of CD8 T cell activity following administration of R-DOTAP plus Ag. This response requires Myd88 but not TRIF or STING. We also show that R-DOTAP stimulates both TLR7 and 9. Collectively, these studies reveal that R-DOTAP stimulates endosomal TLRs, resulting in a Myd88-dependent production of type I IFN. When administered with Ag, this results in potent Ag-specific CD8 T cell responses and antitumor activity. Read More on PubMed

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