Study Evaluating [18F]NOTA-ABY030 for Safety and Tolerability of Indeterminate Primary and/or Metastatic Disease in Head and Neck Squamous Cell Carcinoma

Vanderbilt University Medical Center

Status and phase: Not yet enrolling; Phase 1

Conditions: SCC - Squamous Cell Carcinoma; Metastatic Head and Neck Squamous Cell Carcinoma; Radiotracer; Head and Neck Squamous Cell Carcinoma

Treatments: Procedure: Positron Emission Tomography (PET); Drug: 18F-NOTA-ABY-030; Drug: Cetuximab (EGFR inhibitor)

Study type: Interventional

Funder types: Other

Identifiers

NCT07217028

VICCHNP25055

Details and patient eligibility

About

This Phase I, single-institution, open-label study will evaluate the safety, tolerability, and diagnostic performance of [18F]NOTA-ABY030 PET/CT in patients with head and neck squamous cell carcinoma (HNSCC) who present with indeterminate lesions on standard imaging. The investigational agent is a radiolabeled anti-EGFR affibody designed for rapid clearance and improved tumor-to-background contrast. All participants will receive a 50 mg cetuximab loading dose followed by a bolus of [18F]NOTA-ABY030, with PET/CT imaging performed at defined intervals to assess biodistribution and lesion uptake. The primary objective is to determine safety and tolerability; secondary objectives include radiation dosimetry and comparison of sensitivity and specificity to conventional imaging modalities (MRI, CT, and [18F]FDG-PET/CT). This approach aims to improve diagnostic accuracy, reduce unnecessary biopsies, and streamline treatment decisions for patients with HNSCC.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18 years.

2. Subjects diagnosed with any T stage, any subsite within the head and neck. Subjects with recurrent disease or a new primary will be allowed.

3. Must have evidence of indeterminate metastatic and/or primary SCC based on clinical imaging or Primary SCC with suspicious Lymph Nodes standard image modalities prior to surgical removal

4. Have acceptable lab values, including the following clinical results (if values are considered clinically significant per investigator, participants must be asymptomatic):

   1. Hemoglobin ≥ 9gm/dL
   2. White blood cell count > 3000/mm3
   3. Platelet count ≥ 100,000/mm3
   4. Serum creatinine ≤ 1.5 times upper reference range
   5. Potassium
   6. Magnesium
   7. Phosphorus

Exclusion criteria

1. Myocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); significant liver disease; or unstable angina within 6 months prior to enrollment.
2. Prior severe infusion reactions or hypersensitivity to other monoclonal antibody therapies.
3. Pregnant (based on Screening serum or urine pregnancy test administered before infusions), or breastfeeding.
4. Participants with known hypersensitivity to NOTA-ABY-030, cetuximab, murine, or any of the drug components used in this trial.
5. Subjects with history or evidence of interstitial pneumonitis or pulmonary fibrosis.
6. Severe renal disease or anuria.
7. Participants presenting with a baseline QTcF interval > than 480 milliseconds.
8. Those with an allergy to red meat, a history of tick bites, and alpha-gal syndrome will be given extra consideration.

Trial design

Primary purpose: Supportive Care

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Cohort 1 - Dosimetry (3 Whole Body PET/CT Scans)

Experimental group

Description:

Cohort A will include a minimum of six participants up to 12 participants. These participants will receive a 50 mg intravenous infusion of cetuximab, followed by a bolus injection of \[18F\]NOTA-ABY-030 at a dose of 5 (±1) mCi. To evaluate tracer distribution and radiation exposure, participants in this cohort will undergo three whole-body PET/CT scans at specific timepoints: 0-90 minutes, 120 minutes, and 240 minutes post-injection. Each scan will cover the region from the skull to mid-thigh, with a total imaging time of approximately 90 minutes. This cohort is essential for determining the absorbed dose, organ-specific uptake, identification of critical organs, and the effective dose of the radiopharmaceutical. The data collected from Cohort A will inform safety parameters and support dose optimization for future clinical studies involving \[18F\]NOTA-ABY-030.

Treatment:

Drug: Cetuximab (EGFR inhibitor)

Drug: 18F-NOTA-ABY-030

Procedure: Positron Emission Tomography (PET)

Cohort 2 - (1 Whole Body PET/CT Scan)

Experimental group

Description:

Cohort 2 will include 54 participants. Each participant will receive a 50 mg intravenous infusion of cetuximab, followed by a bolus injection of \[18F\]NOTA-ABY-030 at a dose of 5 (±1) mCi. Imaging for this cohort will be conducted at a single timepoint, approximately 0-240 minutes (±15 minutes) post-injection, based on optimized timing derived from Cohort 1 data. The PET/CT scan for Cohort 2 will cover the region from skull to chest, with a total scan time of approximately 30 minutes. This cohort is designed to evaluate the diagnostic performance of \[18F\]NOTA-ABY-030 in identifying indeterminate metastatic and/or primary lesions in head and neck squamous cell carcinoma (HNSCC), with a focus on sensitivity, specificity, and feasibility of the imaging protocol in a broader patient population.

Treatment:

Drug: Cetuximab (EGFR inhibitor)

Drug: 18F-NOTA-ABY-030

Procedure: Positron Emission Tomography (PET)