Study to Evaluate Immunological Response to PD-1 Inhibition in Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Study Overview
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Brief Summary
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This is a single-center cross-sectional imaging and correlative biomarker study in patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN). Cohort 1 will be patients with unresectable or metastatic SCCHN cancer receiving standard of care (SOC) anti-PD-1 treatment and Cohort 2 will be neoadjuvant study participants who will receive one dose of anti-PD-1 treatment prior to tumor resection or radiation. Blood sampling and tissue biopsies will be collected from both cohorts and both cohorts will undergo two whole body PET(Positron Emission Tomography)/CT(Computed Tomography) imaging with [18F]F-AraG. First scan prior to initiating anti-PD-1 treatment and second scan post initiation of anti-PD-1 treatment in Cohort 1 and prior to tumor resection or radiation in Cohort 2

Detailed Description
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This is a single-center cross-sectional imaging and correlative biomarker study in patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN). Cohort 1 will be patients with unresectable or metastatic SCCHN cancer receiving standard of care (SOC) anti-PD-1 treatment and cohort 2 will be neoadjuvant study participants who will receive one dose of anti-PD-1 treatment prior to tumor resection or radiation. Blood sampling and tissue biopsies will be collected from both cohorts and both cohorts will undergo two whole body PET(Positron Emission Tomography)/CT(Computed Tomography) imaging with [18F]F-AraG. First scan prior to initiating anti-PD-1 treatment and second scan 6-12 weeks post initiation of anti-PD-1 treatment in Cohort1 and within 2-3 weeks of administration of one dose of anti-PD-1 in Cohort 2. This study will help us assess if [18F]F-AraG can be used for noninvasive imaging and assessment of T cell activation and expansion in the tumor microenvironment. Specifically, we will be assessing if there is a correlation between an increase in the imaging signal and an increase in T cell activation (measured directly from the T cells obtained from biopsy specimens). Patients and care providers will not be blinded to any part of this study. Patients will be evaluated one day and one week via telephone visit after each radiopharmaceutical injection for safety follow-up. All adverse events will be recorded. Due to the noninvasive and non-therapeutic nature of the study, potential risks of the study are anticipated to be low.

Official Title
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A Pilot Study to Evaluate Immunological Response to PD-1 Inhibition in Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Conditions
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Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
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* Drug: [18F]F-AraG PET Scan, baseline + post anti-PD-1 therapy.
* Drug: [18F]F-AraG PET Scan, baseline + post anti-PD-1 therapy.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable or metastatic SCCHN. Localized SCCHN. >18 years old. Willing and able to sign consent form. Have standard of care biopsy or resection planned or tumors amenable to serial biopsies. For patients with reproductive potential must undergo counseling to understand unknown risks to resultant progeny. Exclusion Criteria: Diagnosis of immunodeficiency or active autoimmune condition. Active tuberculosis Prior exposure to PD-1 or PD-LI treatment Prior systemic chemotherapy within 2 weeks of planed anti-PD1 treatment. Received a live vaccine within 30 days of planned PD-1 start date. Pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 Patients with M/R SCCHN<br>Patients with unresectable and metastatic SCCHN cancer who will receive anti-PD-1 treatment under SOC. SOC treatments currently include nivolumab and pembrolizumab (anti-PD-1 treatment). The protocol may be amended to include other agents should they become SOC. Patients will receive a baseline [18F]F-AraG PET/CT scan and another [18F]F-AraG PET/CT scan 6 to 12 weeks after anti-PD-1 dose. | Drug: [18F]F-AraG PET Scan, baseline + post anti-PD-1 therapy.<br>* Baseline: Blood sampling, tumor biopsy, [18F]F-AraG PET/CT scan within two weeks prior to standard of care anti-PD-1 therapeutic dose. Anti PD-1 per standard of care Blood sampling and tumor biopsy within 2-3 weeks after first anti-PD-1 SOC dose. [18F]F-AraG PET/CT scan 6 - 12 weeks post first anti-PD-1 dose.<br>|
| Experimental: Cohort 2 Patients with de novo SCCHN<br>Patients with de novo SCCHN prior to initiation of anti-cancer treatment (e.g., radiation, chemoradiation, or surgery). Patients will receive ONE DOSE of the anti-PD-1 treatment, after the baseline [18F]F-AraG PET/CT scan, baseline blood and tumor tissue collection. Patients will receive a second [18F]F-AraG PET/CT scan 2 - 3 weeks after the one dose of anti-PD-1 treatment. | Drug: [18F]F-AraG PET Scan, baseline + post anti-PD-1 therapy.<br>* Baseline: Blood sampling, tumor biopsy, [18F]F-AraG PET/CT scan within two weeks prior to treatment. Anti PD-1, single dose Blood sampling, tumor biopsy and [18F}F-AraG PET/CT scan within 2-3 weeks after single dose of anti-PD-1 treatment. For patients having surgical resection, biopsy will be immediately prior to resection or from sample of resection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-invasive assessment of T cell activation at tumor site from anti-PD1 therapy as measured by signal changes with VisAcT imaging biomarker | Assess whether [18F]F-AraG accumulation at the site of inflammation can be used for noninvasive imaging and assessment of T cell activation and expansion in the tumor microenvironment. Specifically, we will be assessing if there is a correlation between an increase in the imaging signal and an increase in T cell activation (measured directly from the T cells obtained from biopsy specimens). | Baseline and 6 to 12 weeks after initial anti-PD-1 dose in Cohort 1 and Baseline and 2 to 3 weeks after anti-PD-1 dose in Cohort 2. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success rate for collection of paired blood and tissue samples pre and post immunotherapy treatment in each Cohort. | Explore the feasibility of deep sequencing the tumor cells and also the paired T cell receptor alpha and beta chains of the expanding T cells from the same patient before and after the administration of a Moab directed against PD-1. | 2 to 3 weeks post initial anti-PD-1 dose. |