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

Not Applicable

Not yet recruiting

• Conditions: SCC - Squamous Cell Carcinoma; Radiotracer; Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Squamous Cell Carcinoma
• Interventions: Drug: Cetuximab (EGFR inhibitor); Drug: 18F-NOTA-ABY-030; Procedure: Positron Emission Tomography (PET)

• Registration Number: NCT07217028
• Lead Sponsor: Vanderbilt-Ingram Cancer Center

Brief Summary

This Phase I clinical trial evaluates the safety, tolerability, and diagnostic performance of a novel PET imaging agent, \[18F\]NOTA-ABY030, 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 to improve tumor specificity and reduce background signal, potentially enhancing diagnostic accuracy. Participants receive a loading dose of cetuximab followed by \[18F\]NOTA-ABY030, with PET/CT imaging performed at defined intervals to assess biodistribution and lesion uptake. The study aims to determine the agent's safety profile, calculate radiation dosimetry, and compare its sensitivity and specificity to conventional imaging modalities such as MRI, CT, and \[18F\]FDG-PET/CT. This approach may reduce unnecessary biopsies and improve staging accuracy, ultimately streamlining treatment decisions for patients with HNSCC.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-10
• Study First Submitted: 2025-10-13
• Study First Submitted QC: 2025-10-13
• Last Update Submitted: 2025-10-13
• Study First Posted: 2025-10-15
• Last Update Posted: 2025-10-15
• Study Start: 2025-11-01
• Primary Completion: 2029-11
• Study Completion: 2031-04-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 1 - Dosimetry	Cetuximab (EGFR inhibitor)	Cohort A will include six 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.
Cohort 1 - Dosimetry	18F-NOTA-ABY-030	Cohort A will include six 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.
Cohort 1 - Dosimetry	Positron Emission Tomography (PET)	Cohort A will include six 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.
Cohort 2	Cetuximab (EGFR inhibitor)	Cohort B 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 240 minutes (±15 minutes) post-injection, based on optimized timing derived from Cohort A data. The PET/CT scan for Cohort B 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.
Cohort 2	18F-NOTA-ABY-030	Cohort B 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 240 minutes (±15 minutes) post-injection, based on optimized timing derived from Cohort A data. The PET/CT scan for Cohort B 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.
Cohort 2	Positron Emission Tomography (PET)	Cohort B 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 240 minutes (±15 minutes) post-injection, based on optimized timing derived from Cohort A data. The PET/CT scan for Cohort B 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.

Primary Outcome Measures

Name	Time	Method
Determine safety and tolerability of [18F]NOTA-ABY-030 in human subjects.	From infusion to 7 days post-infusion	As determined by the number of adverse events (AEs) that are possibly or probably related to the study drug within 24 hours after infusion. Dose limiting toxicities will be defined as an AE grade \>2 that is clinically significant and attributable to the study drug.

Secondary Outcome Measures

Name	Time	Method
Determination of the radiation dosimetry for [18F]NOTA-ABY-030 in human subjects.	From infusion to 7 days post-infusion	The dosimetry for \[18F\]NOTA-ABY-030 will be determined to be the absorbed dose, organ specific uptake, critical organs, and effective dose for this first-in-human radiopharmaceutical.
Compare sensitivity and specificity of standard of care imaging modalities (MRI, CT, and/or [18F]FDG PET/CT) to [18F]NOTA-ABY-030-PET/CT for detection of indeterminate metastatic and/or primary lesion(s) in HNSCC	From infusion to 7 days post-infusion	The specificity and sensitivity of \[18F\]NOTA-ABY-030 will be compared to the specificity and sensitivity of standard of care imaging obtained (MRI, CT, and/or \[18F\]FDG PET/CT) for identification of metastatic or primary lesion.

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States