NCT07217028

Brief Summary

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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25

participants targeted

Target at P25-P50 for phase_1

Timeline
53mo left

Started Apr 2026

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress2%
Apr 2026Sep 2030

First Submitted

Initial submission to the registry

October 13, 2025

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 15, 2025

Completed
6 months until next milestone

Study Start

First participant enrolled

April 1, 2026

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2029

Expected
1.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2030

Last Updated

April 29, 2026

Status Verified

February 1, 2026

Enrollment Period

3 years

First QC Date

October 13, 2025

Last Update Submit

April 23, 2026

Conditions

Keywords

unknown primarycancerhnsccscc

Outcome Measures

Primary Outcomes (1)

  • Assess number, grade and severity of adverse events to determine safety and tolerability of [18F]NOTA-ABY-030 in human subjects.

    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.

    From infusion to 7 days post-infusion

Secondary Outcomes (2)

  • Determination of the radiation dosimetry for [18F]NOTA-ABY-030 in human subjects.

    From infusion to 7 days post-infusion

  • 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

Other Outcomes (1)

  • Determine the sensitivity and specificity of [18F]NOTA-ABY-030 for the detection of indeterminate metastatic and/or primary lesion(s) in HNSCC.

    From day of infusion to 36 months post-infusion

Study Arms (2)

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

EXPERIMENTAL

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.

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

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

EXPERIMENTAL

Cohort 2 will include a minimum of thirteen 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.

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

Interventions

Given IV

Cohort 1 - Dosimetry (3 Whole Body PET/CT Scans)Cohort 2 - (1 Whole Body PET/CT Scan)

Given Bolus Injection

Cohort 1 - Dosimetry (3 Whole Body PET/CT Scans)Cohort 2 - (1 Whole Body PET/CT Scan)

Undergo PET/CT

Cohort 1 - Dosimetry (3 Whole Body PET/CT Scans)Cohort 2 - (1 Whole Body PET/CT Scan)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 18 years.
  • Subjects diagnosed with any T stage, any subsite within the head and neck. Subjects with recurrent disease or a new primary will be allowed.
  • 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
  • Have acceptable lab values, including the following clinical results (if values are considered clinically significant per investigator, participants must be asymptomatic):
  • Hemoglobin ≥ 9gm/dL
  • White blood cell count \> 3000/mm3
  • Platelet count ≥ 100,000/mm3
  • Serum creatinine ≤ 1.5 times upper reference range
  • Potassium
  • Magnesium
  • Phosphorus

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Carcinoma, Squamous CellSquamous Cell Carcinoma of Head and NeckNeoplasms

Interventions

CetuximabMagnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasms, Squamous CellHead and Neck NeoplasmsNeoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsSpectrum AnalysisChemistry Techniques, AnalyticalInvestigative Techniques

Study Officials

  • Eben Rosenthal, MD

    Vanderbilt University Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
SUPPORTIVE CARE
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Barry and Amy Baker Professor and Department Chair

Study Record Dates

First Submitted

October 13, 2025

First Posted

October 15, 2025

Study Start

April 1, 2026

Primary Completion (Estimated)

April 1, 2029

Study Completion (Estimated)

September 1, 2030

Last Updated

April 29, 2026

Record last verified: 2026-02

Locations