Non-invasive Measurement of PD-L1 Levels With Positron Emission Tomography (PET) in Head and Neck Malignancies and Intracranial Metastases

Pilot Study of Non-invasive Measurement of PD-L1 Levels With Positron Emission Tomography (PET) in Head and Neck Malignancies and Intracranial Metastases

This study aims to determine the feasibility of non-invasive quantitative PD-L1 measurement using [a novel PD-L1 positron emission tomography (PET) tracer and perform immunohistochemistry based measurement of PD-L1 levels within resected lesions in head and neck cancer and brain metastases.

Study Overview

• Status: Terminated
• Conditions: Cancer Head Neck; Metastatic Cancer; Metastatic Lung Cancer
• Intervention / Treatment: Drug: adnectin 18F-BMS-986192 Head and Neck Cancer; Drug: adnectin 18F-BMS-986192 Brain Metastases

Detailed Description

This study aims to validate a non-invasive quantitative imaging method of whole tumors using a novel PD-L1 positron emission tomography (PET) tracer in patients with head and neck cancer who undergo resection of primary tumor and locoregional lymph node metastases thus providing an excellent model to perform correlative studies with immunohistochemistry (IHC).

The investigators will extend the study to patients with brain metastases because there is a critical need for a non-invasive test for PD-L1 in this population, as biopsy of these lesions is rare.

In this study, the investigators will image patients with brain metastases, which are predominantly from lung cancer and melanoma, that are planned to undergo biopsy. The ultimate goal of this research is to validate quantitative PD-L1 PET imaging in determining PD-L1 expression within primary and metastatic cancer without the need for biopsy and identify parameters of PD-L1 quantitative PET that will allow its translation into clinical practice. This method can then be used to determine which patients may benefit from immunotherapy.

The primary objective of this study aims to test the difference in non-invasive quantitative PD-L1 PET measures (VT) of lesions between different groups of PD-L1 levels (PD-L1 ≥90% vs <1%) in head and neck cancer primary lesions.

Secondary objectives:

1. To establish lesion level association between immunohistochemistry measures of PD-L1 levels within primary head and neck cancer lesions (as the outcome) and PD-L1 PET measures (VT);
2. To establish lesion level association between immunohistochemistry measures of PD-L1 levels within locoregional metastases within the neck and resected normal lymph nodes (as the outcome) and PD-L1 PET measures (VT).
3. To establish lesion level association between the degree of tumor inflammatory cell infiltration on IHC in primary head and neck squamous cell carcinoma (SCC) lesions (as the outcome) and PD-L1 PET measures (VT);
4. To establish lesion level association between the degree of tumor inflammatory cell infiltration on IHC in metastatic head and neck SCC lesion (as the outcomes) and PD-L1 PET measures (VT).

Tertiary objective:

To establish lesion level correlation of IHC measures of total/tumor/inflammatory cell PD-L1 levels to PD-L1 (VT) on PET in brain metastases

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University PET Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria for Head and Neck Cancer:

• Patients with resectable squamous cell carcinoma of the oropharynx (HPV positive and HPV negative).
• Resectability will be confirmed by a surgical co-investigator.
• If available, HPV-association determined by institutional p16 testing (CINtec antibody demonstrating strong and diffuse nuclear and cytoplasmic staining is at least 70% of cells).
• Absolute neutrophil count (ANC) > 1500/microliter, absolute lymphocyte count (ALC) >1000/microliter, hemoglobin > 9 g/dl, platelets > 100,000/microliter.
• aspartate aminotransferase (AST) and alanine transaminase (ALT) < 5 x upper limit of normal. Bilirubin < 1.5 x upper limit of normal.
• Albumin > 0 g/dl.
• Creatinine < 5 x upper limit of normal.
• Women of child-bearing potential must have a negative serum pregnancy test within 7 days prior to treatment

Inclusion Criteria for Brain Metastases:

• Patients with brain metastases
• Tumor size equal or greater than 1 cm
• Resectability or need for laser interstitial thermal therapy (LITT) will be confirmed by a surgical co-investigator.
• Absolute neutrophil count (ANC) > 1500/microliter, absolute lymphocyte count (ALC) >1000/microliter, hemoglobin > 9 g/dl, platelets > 100,000/microliter
• AST and ALT < 5 x upper limit of normal. Bilirubin < 1.5 x upper limit of normal.
• Albumin > 0 g/dl.
• Creatinine < 5 x upper limit of normal.
• Women of child-bearing potential must have a negative serum pregnancy test within 7 days prior to treatment

Exclusion Criteria for Head and Neck Cancer:

• Medical contraindication to surgery.
• Full dose anticoagulation.
• Concomitant invasive malignancy, or malignancy within 2 years except for hormonally responsive breast or prostate cancer, resected non-melanoma skin cancer, resected uterine cervical carcinoma.
• Inability to give informed consent.
• Prior systemic therapy, radiation or gross resection for the tumor under study.
• Women may not be pregnant or breast-feeding.
• Receipt of other systemic therapy including investigational agents, radiation or gross resection for treatment of the tumor under study.

Exclusion Criteria for Brain Metastases:

• Medical contraindication to brain surgery.
• Full dose anticoagulation.
• Inability to give informed consent.
• Women may not be pregnant or breast-feeding.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Head and neck cancer; Participants with head and neck squamous cell carcinoma who plan to undergo tumor resection and lymph node resection.	Drug: adnectin 18F-BMS-986192 Head and Neck Cancer; Head and Neck Cancer: PET imaging will be performed after initial diagnosis and within 2 weeks of MRI or CT of the neck done as standard of care. MRI will include T1 weighted pre and post gadolinium spin echo, diffusion weighted imaging, and T2 weighted imaging. CT of the head and neck with contrast will be performed per standard clinical protocol. Patients will get one intravenous line and one radial artery line placed prior to imaging and up to 5.5mCi (204MBq) of [18F] PDL192 tracer will be administered intravenously, as a bolus, once the patient is positioned on the scanner. 42 PET data will be acquired at single bed position and in list mode for 120 min after the start of tracer administration. Samples will be drawn from radial artery line.; Other Names: [18F]PDL192
Experimental: Brain Metastases; Participants with metastases to the brain from melanoma, lung cancer, breast cancer.	Drug: adnectin 18F-BMS-986192 Brain Metastases; Brain Metastases: Recruited patients will undergo standard clinical MRI within 2 weeks prior to PET, including T1 weighted pre- and post-gadolinium spin-echo and gradient-echo imaging, diffusion weighted imaging, susceptibility weighted imaging (2D SWI), T2 weighted imaging, 3D FLAIR, and combined DCE and dynamic susceptibility contrast (DSC) perfusion (DCE perfusion will be performed first, DSC perfusion will utilize T2 spin echo images). DCE perfusion will be processed on syngo Tissue 4D software (Siemens). DSC perfusion will be processed with syngo MR Perfusion Engine (Siemens). Patients will get one intravenous line and one radial artery line placed prior to imaging and up to 5.5mCi (204MBq) of [18F] PDL192 tracer will be administered intravenously, as a bolus, once the patient is positioned on the scanner. 42 PET data will be acquired at single bed position and in list mode for 120 min after the start of tracer administration. Samples will be drawn from radial artery line.; Other Names: [18F]PDL192

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-invasive quantitative PD-L1 levels will be measured using PET measures (VT) of lesions for the groups of PD-L1 levels (PD-L1 ≥90% vs <1%, PD-L1 ≥50% vs <1%) in head and neck cancer primary lesions	To test the difference in non-invasive quantitative PD-L1 PET measures (VT) of lesions between different groups of PD-L1 levels (PD-L1 ≥90% vs <1%) in head and neck cancer primary lesions	from with in 2 weeks perioperative up to postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunohistochemistry vs PET measure of PD-L1 levels in head and neck cancer primary lesion	To establish lesion level association comparing immunohistochemistry measures of PD-L1 levels within primary head and neck cancer lesions and PD-L1 PET measures (VT) using Pearson correlation between pathology based measure and imaging based measure.	from with in 2 weeks perioperative up to postoperative
Immunohistochemistry vs PET measure of PD-L1 levels in head and neck cancer locoregional neck metastatic lesions and resected normal lymph nodes	To establish lesion level association comparing immunohistochemistry measures of PD-L1 levels within locoregional metastases within the neck and resected normal lymph nodes (as the outcome) and PD-L1 PET measures (VT) using Pearson correlation between pathology based measure and imaging based measure.	from with in 2 weeks perioperative up to postoperative
Immunohistochemistry vs PET measure of infiltrating inflammatory cells in head and neck cancer primary lesion	To establish lesion level association comparing the degree of tumor inflammatory cell infiltration seen on IHC in primary head and neck SCC lesions (as the outcome) and PD-L1 PET measures (VT) using Pearson correlation between pathology based measure and imaging based measure.	from with in 2 weeks perioperative up to postoperative
Immunohistochemistry vs PET measure of infiltrating inflammatory cells in head and neck cancer locoregional neck metastatic lesions and resected normal lymph nodes	To establish lesion level association comparing the degree of tumor inflammatory cell infiltration on IHC in metastatic head and neck SCC lesion (as the outcomes) and PD-L1 PET measures (VT) using Pearson correlation between pathology based measure and imaging based measure.	from with in 2 weeks perioperative up to postoperative

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunohistochemistry vs PET measure of PD-L1 levels within resected brain metastasis tumor cells	To establish lesion level correlation of IHC measures of total/tumor/inflammatory cell PD-L1 levels compared to PD-L1 (VT) on PET in brain metastases using Pearson correlation between pathology based measure and imaging based measure.	from with in 2 weeks perioperative up to postoperative

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mariam S Aboian, MD PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2023
• Primary Completion (Actual): January 31, 2024
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: June 1, 2022
• First Submitted That Met QC Criteria: June 1, 2022
• First Posted (Actual): June 7, 2022

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms
• Other Study ID Numbers: 2000031462; 1R21CA259964-01A1 (U.S. NIH Grant/Contract)

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
• product manufactured in and exported from the U.S.: No