The purpose of this study is to evaluate anti-PD-1 Neoadjuvant therapy in Basal cell
carcinoma to provide a better outcome when administered prior to surgery and provide a
therapeutic strategy to avoid surgery altogether. The study team will gather information
about how Basal cell carcinoma responds to Pembrolizumab prior to surgery and to gather
information about recurrence rates.
Pembrolizumab, is an investigational (experimental) drug that may improve the response of the
immune system against cancer. Pembrolizumab is a manufactured antibody, much like the
antibodies usually made by the human body to fight off infection. The idea behind developing
this experimental drug is to stimulate the body's immune system to kill cancer cells.
Pembrolizumab antibody has been specifically made to block a program cell death-1 (PD-1)
protein receptor, which is found on cells of the immune system. PD-1 receptor seems to slow
down the immune response. Blocking PD-1 with pembrolizumab antibody may make the immune
response more active and may improve the response of the immune system against cancer.
Pembrolizumab is currently FDA approved for use in other malignancies. It has been used to
treat a number of other diseases such as certain types of lung cancer, cervical cancer and
lymphoma. The use of Pembrolizumab in this study is experimental because it is not approved
by the Food and Drug Administration (FDA) for use in the treatment of Basal cell carcinoma.
This is a phase 1 study looking at anti-PD-1 Neoadjuvant therapy in Basal cell carcinoma in
participants with locoregionally advanced, but resectable basal cell carcinoma of the head
and neck. Participants will undergo fine cut CT imaging (head and neck) and treatment with
the study drug pembrolizumab.
The primary objective of this study is to evaluate pathologic response to pre-operative
treatment of pembrolizumab in the study group.
Secondary objectives of this study include assessing safety of the intervention, and
assessing phenotyping immune infiltrates in non-pathology complete responders (pCRs), as well
as assessment of changes to the systemic immune system (e.g. peripheral blood lymphocytes
(PBLs)) in pCRs vs partial responders (pPR) vs non responders.
The exploratory objective will include assessing one-year recurrence rates after completion
of NeoAdjuvant-Adjuvant therapy.
- Advanced basal cell carcinoma for the purposes of this study will be defined by
features associated with increased risk of recurrence including at least one of the
- Meeting indication for post-operative radiation
- Perineural invasion in multiple nerves
- Female participants: A female participant is eligible to participate if she is not
pregnant (see Appendix 3), not breastfeeding, and at least one of the following
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
- A female of child bearing potential who agrees to follow the contraceptive
guidance in Appendix 3 during the treatment period and for at least 150 days
after the last dose of study treatment.
- The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial.
- Have a histological confirmation of diagnosis of Basal cell carcinoma (BCC) of any
subtype (e.g. Nodular, aggressive infiltrative, etc).
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Evaluation of ECOG is to be performed within 7 days prior to the date of
allocation/randomization. Patients with PS 2 will be considered if good rationale
provided and discussed with Merck study team.
- Have adequate organ function as defined in the following table (Table 1). Specimens
must be collected within 10 days prior to the start of study treatment.
- Must not be on active immunosuppression, have a history of life threating virus, have
had other (beside non-melanoma skin cancers, or recent indolent cancers e.g.: resected
low grade prostate cancer) cancer diagnoses in the last two years, or have had
immunotherapy of any kind within the last 2 years.
Must not have a history of (non-infectious) pneumonitis that required steroids or has
- Participants who require adjuvant radiation are eligible.
Adequate Organ Function Laboratory Values Note: This table includes eligibility-defining
laboratory value requirements for treatment; laboratory value requirements should be
adapted according to local regulations and guidelines for the administration of specific
- Absolute neutrophil count (ANC)
- >= 1500/μL
- Platelets >= 100 000/μL
- >= 9.0 g/dL or >= 5.6 mmol/L ---- Criteria must be met without erythropoietin
dependency and without packed red blood cell (pRBC) transfusion within last 2
- Creatinine OR Measured or calculatedb creatinine clearance (GFR can also be used in
place of creatinine or CrCl) --- <=1.5 × ULN OR >= 30 mL/min for participant with
creatinine levels > 1.5 × institutional ULN ---- Creatinine clearance (CrCl) should be
calculated per institutional standard.
- Total bilirubin
--- <=1.5 ×ULN OR direct bilirubin <= ULN for participants with total bilirubin levels
>1.5 × ULN
- Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) [AST (SGOT)] and
alanine aminotransferase (serum glutamic pyruvic transaminase) [ALT (SGPT)] --- <= 2.5
× ULN (≤5 × ULN for participants with liver metastases)
- International normalized ratio (INR) OR prothrombin time (PT)
- Activated partial thromboplastin time (aPTT) --- <= 1.5 × ULN unless participant is
receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of
intended use of anticoagulants
- A female of child bearing potential who has a positive urine pregnancy test within 72
hours prior to enrollment (see Appendix 3). If the urine test is positive or cannot be
confirmed as negative, a serum pregnancy test will be required. In the event that 72
hours have elapsed between the screening pregnancy test and the first dose of study
treatment, another pregnancy test (urine or serum) must be performed and must be
negative in order for subject to start receiving study medication.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
- Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks prior to enrollment. Participants must have recovered from all AEs due
to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy
may be eligible. If participant received major surgery, they must have recovered
adequately from the toxicity and/or complications from the intervention prior to
starting study treatment.
- Has received prior radiotherapy within 2 weeks of start of study treatment.
Participants 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 study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (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.
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
Note: Participants who have entered the follow-up phase of an investigational study may
participate as long as it has been 4 weeks after the last dose of the previous
- 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.
- Has a known additional malignancy that is progressing or has required active treatment
within the past 2 years. Note: Participants with other types of skin carcinoma or
carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone
potentially curative therapy are not excluded.
- Has known active CNS metastases and/or carcinomatous meningitis. Participants 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 the repeat imaging should be performed during study screening), clinically
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 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 (eg. thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
- Has a history of (non-infectious) pneumonitis that required steroids or has current
- Has an active infection requiring systemic therapy.
- Has a known history of Human Immunodeficiency Virus (HIV).
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as: HCV RNA >800,000 IU/L is
detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required
unless mandated by local health authority.
- Has a known history of active TB (Bacillus Tuberculosis).
- 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 known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
- 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 trial treatment.
- History of Hedgehog inhibitor treatment for any reason.
- History of allogeneic tissue/solid organ transplant whether or not on active