Evaluation of [18F]AlF-NOTA-PCP2 PET/CT for PD-L1 Detection in Malignant Tumors

Phase 1

• Conditions: Glioblastoma (GBM); Head and Neck Squamous Cell Carcinoma; Non-Small Cell Lung Cancer; Esophageal Cancer

• Registration Number: NCT06690216
• Lead Sponsor: Man Hu

Brief Summary

This phase I/II clinical trial evaluates the safety, efficacy, and prognostic potential of \[18F\]AlF-NOTA-PCP2 PET/CT imaging in assessing PD-L1 expression in malignant tumors, including glioblastoma, head and neck squamous cell carcinoma, non-small cell lung cancer, and esophageal cancer. The primary aim is to establish the correlation between \[18F\]AlF-NOTA-PCP2 uptake and PD-L1 expression in tumor tissues, while secondary objectives include evaluating its role in predicting clinical outcomes such as progression-free survival (PFS) and overall survival (OS). By providing a non-invasive, quantitative, and reproducible method for assessing PD-L1, this study aims to refine patient stratification and improve the precision of immunotherapy decision-making.

Detailed Description

This phase I/II clinical trial is designed to explore the utility of \[18F\]AlF-NOTA-PCP2 PET/CT in evaluating PD-L1 expression and its prognostic implications in patients with malignant tumors (glioblastoma, head and neck squamous cell carcinoma, non-small cell lung cancer, and esophageal cancer). The study involves at least 20 patients (5 per tumor type) who will undergo a pre-treatment PET/CT scan following an intravenous injection of \[18F\]AlF-NOTA-PCP2. The primary endpoints include the safety of the imaging protocol and the correlation between \[18F\]AlF-NOTA-PCP2 uptake (SUV values) and PD-L1 expression determined through immunohistochemistry (IHC). Secondary endpoints explore the dynamic changes in SUV values in patients undergoing multiple scans and their relationship with clinical outcomes.

Scientific and Technical Rationale:

\[18F\]AlF-NOTA-PCP2 is a novel radiotracer with high specificity for PD-L1, enabling non-invasive imaging of its expression in vivo. This imaging approach complements traditional immunohistochemical methods by offering whole-body assessment, eliminating the need for repeated biopsies, and providing insights into the tumor microenvironment. This study seeks to validate its application in clinical oncology, bridging molecular imaging with biomarker-guided therapeutic strategies.

Study Methods:

Patients will receive a single intravenous dose of \[18F\]AlF-NOTA-PCP2 (adjusted for body weight), followed by a whole-body PET/CT scan after one hour. Images will be analyzed independently by two experienced nuclear medicine specialists. Tumor biopsies will be collected to measure PD-L1 expression via IHC, and blood samples will be assessed for circulating and exosomal PD-L1 biomarkers. For patients undergoing multiple scans, changes in radiotracer uptake will be tracked to monitor treatment response.

Data Analysis:

SUV values will be correlated with PD-L1 expression levels, clinical factors (e.g., tumor stage, histology), and patient outcomes (PFS, OS). Statistical analyses, performed using SPSS 29.0, will include primary correlations and secondary evaluations of imaging-based dynamic changes and their relationship with therapeutic efficacy.

Significance:

This trial will provide critical data on the feasibility of \[18F\]AlF-NOTA-PCP2 PET/CT imaging in clinical oncology. Its potential to stratify patients based on PD-L1 expression and predict therapy response could transform personalized cancer care, optimizing immunotherapy outcomes and minimizing unnecessary treatments.

Timeline:

Patient enrollment is expected to last 12 months, with an additional 3 months of follow-up for data collection and analysis.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2024-03-30
• Status Verified: 2024-11
• Study First Submitted: 2024-11-13
• Study First Submitted QC: 2024-11-13
• Study First Posted: 2024-11-15
• Last Update Submitted: 2024-11-15
• Last Update Posted: 2024-11-19
• Primary Completion: 2025-10-31
• Study Completion: 2026-10-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Signed informed consent obtained.
• Age ≥ 18 years, any gender.
• Pathologically confirmed malignant tumors, including:
• Glioblastoma
• Head and neck squamous cell carcinoma
• Non-small cell lung cancer
• Esophageal cancer
• Detectable PD-L1 expression in tumor tissue (based on immunohistochemistry or biopsy).
• Measurable disease with at least one residual tumor lesion.
• ECOG performance status of 0-1.
• No contraindications to [18F]AlF-NOTA-PCP2 PET/CT imaging.
• Willing and able to comply with study procedures and follow-up visits.

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Exclusion Criteria

• Participation in another interventional clinical trial.
• Failure to recover from toxic effects or complications of prior interventions (≤ grade 1 or baseline levels, excluding fatigue or hair loss).
• Pregnant or breastfeeding women.
• Severe or uncontrolled systemic diseases, including:
• Major, symptomatic arrhythmias or significant ECG abnormalities (e.g., complete left bundle branch block, second-degree or higher heart block, or ventricular arrhythmias).
• Unstable angina or congestive heart failure (NYHA class ≥ 2).
• Any arterial thrombotic or embolic events within 6 months before enrollment (e.g., myocardial infarction, cerebrovascular accident, transient ischemic attack).
• Active or uncontrolled infections requiring systemic treatment.
• Severe psychiatric disorders affecting study participation.
• Any medical history, laboratory abnormality, or condition that may:
• Interfere with study results.
• Affect patient participation.
• Pose an unacceptable risk as determined by the investigator.
• Women of childbearing potential without a negative pregnancy test prior to study entry.
• Known allergy or hypersensitivity to [18F]AlF-NOTA-PCP2 or any component of the radiopharmaceutical.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Assessment of [18F]AlF-NOTA-PCP2 PET/CT imaging for PD-L1 expression in malignant tumors	Pre-treatment imaging, within 1-7 days before treatment initiation.	This outcome measure will assess the safety and efficacy of \[18F\]AlF-NOTA-PCP2 PET/CT in detecting PD-L1 expression in malignant tumors (glioblastoma, head and neck squamous cell carcinoma, non-small cell lung cancer, and esophageal cancer). This will include evaluating the correlation between \[18F\]AlF-NOTA-PCP2 uptake and PD-L1 expression as determined by immunohistochemistry (IHC).

Secondary Outcome Measures

Name	Time	Method
[18F]AlF-NOTA-PCP2 PET/CT imaging as a prognostic biomarker in malignant tumors	Up to 1 year of follow-up for clinical outcomes (PFS, OS).	This outcome will evaluate the prognostic value of \[18F\]AlF-NOTA-PCP2 PET/CT imaging in predicting clinical outcomes, including progression-free survival (PFS) and overall survival (OS), based on tumor PD-L1 expression.

Trial Locations

Locations (1)

Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences; 🇨🇳 Jinan, Shandong, China