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
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.
- 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
- 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.
- 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
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
- 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