Neoplasms

All Conditions

Carcinoma

Carcinoma, Basal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Basal Cell

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants will undergo fine cut CT imaging (head and neck) followed by at least 4 doses of pembrolizumab q 3 weeks. After the 4th dose of pembrolizumab as appropriate, patients will undergo standard surgical resection, with all non-marginal tissue as well as the pre-op biopsy to be stored for collateral research. 2 weeks after initial flap or graft insert (which would be equivalent to stage 1 of a forehead flap) patients would continue for a total of approximately 1 year of pembrolizumab q 3 weeks (another 13 doses, thus 17 doses total).

Post Fine-cut CT: 4 doses of pembrolizumab (200mg) IV q 3 weeks. Post standard resection and reconstruction: 1 year of pembrolizumab (200mg) q 3 weeks (another 13 doses, thus 17 doses total)

Non-marginal tissue as well as pre-op biopsy tissue to be stored

Tissue collection

Brian Gastman, MD

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.

Neoadjuvant-Adjuvant Pembrolizumab in Resectable Advanced Basal Cell Carcinoma of H&N

A Phase 1B, Single Arm Study of Neoadjuvant-Adjuvant Pembrolizumab in Resectable Advanced Basal Cell Carcinoma of the Head and Neck to Assess for Pathologic Responses in the Tumor Microenvironment

Individual participant data will not be shared but the study team expects to publish the data from this trial

Number of Tumor Infiltrating Lymphocytes (TILs).

Blood for this outcome will be collected at baseline, at day 64 and at recurrence up to 2 years.

Study team will record the phenotypes of the TILs and PBMCs prior and post treatment, determined by their markers, including CD3, CD4, CD8, perforin, FasL, Granzyme, PD-1, TIM-3, Lag-3, TIGIT, Foxp3, GITR, CD25, CD27, and CD28 and markers for myeloid derived suppressor cells.

Blood for this outcome will be collected at baseline, at day 64 and at recurrence up to 2 years.

Study team will also construct a transcriptional profile of the tumor microenvironment by RNA-sequencing the tumor biopsy (tissue) prior and post the pembrolizumab treatment.

Tissue for this outcome will be collected at baseline, at surgery and at recurrence up to 2 years.

Changes to the systemic immune system (PBLs) in pCRs vs partial responders vs non responders as measured by changes in percent of main PBL population (CD3, CD4, CD8)

Pathologic response as assessed by change in tumor volume. Lesions measured between baseline and surgery using RECIST 1.1 criteria

Safety assessed by number of participants experiencing a grade 3 or higher Adverse Event

Number of changes to surgical field which could negatively influence resection such as excessive inflammation or infection.

Rates of phenotyping immune infiltrates in non pCR characterized as 'rare', 'moderate', or 'brisk'.

Blood for this outcome will be collected at baseline, at day 64 and at recurrence up to 2 years.

One-year recurrence ratesafter completion of neoadjuvant-adjuvant therapy

One-year recurrence rates after pembrolizumab neoadjuvant therapy

Spots Global Cancer Trial Database for basal cell carcinoma of the head and neck