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

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

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

Study Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma of the Head and Neck
• Intervention / Treatment: Drug: [18F]F-AraG PET Scan, baseline + post anti-PD-1 therapy.; Drug: [18F]F-AraG PET Scan, baseline + post anti-PD-1 therapy.

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 Patients with M/R SCCHN; 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.; 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.; Drug: [18F]F-AraG PET Scan, baseline + post anti-PD-1 therapy.; 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.
Experimental: Cohort 2 Patients with de novo SCCHN; 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.; 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.; Drug: [18F]F-AraG PET Scan, baseline + post anti-PD-1 therapy.; 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.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: CellSight Technologies, Inc.
• Collaborators: Stanford University
• Investigators: Study Director: A. Dimitrios Colevas, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: April 18, 2017
• First Submitted That Met QC Criteria: April 21, 2017
• First Posted (Actual): April 26, 2017

Study Record Updates

• Last Update Posted (Actual): December 5, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: 40425; ENT0061 (Other Identifier: Stanford University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No