Clinical trial NCT06690216: Evaluation of [18F]AlF-NOTA-PCP2 PET/CT for PD-L1 Detection in Malignant Tumors
Official title: Evaluation of the Value of [18F]AlF-NOTA-PCP2 PET/CT for PD-L1 Detection in Malignant Tumors
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
PHASE2
Conditions: Glioblastoma (GBM)
Head and Neck Squamous Cell Carcinoma
Non-Small Cell Lung Cancer
Esophageal Cancer
Keywords: PET/CT
PD-L1 expression
[18F]AlF-NOTA-PCP2
Glioblastoma
Head and neck squamous cell carcinoma
Non-small cell lung cancer
Esophageal cancer
Immunotherapy guidance
Tumor biomarker imaging
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
First posted: 2024-11-15
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a Phase I/II, single-center, interventional clinical trial assessing the safety, efficacy, and prognostic value of \[18F\]AlF-NOTA-PCP2 PET/CT in evaluating PD-L1 expression in patients with malignant tumors. The study involves pre-treatment imaging with \[18F\]AlF-NOTA-PCP2 PET/CT, followed by correlation with PD-L1 expression in tumor samples and clinical outcomes.
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Assessment of [18F]AlF-NOTA-PCP2 PET/CT imaging for PD-L1 expression in malignant tumors
timeFrame: Pre-treatment imaging, within 1-7 days before treatment initiation.
Secondary outcomes:
measure: [18F]AlF-NOTA-PCP2 PET/CT imaging as a prognostic biomarker in malignant tumors
timeFrame: Up to 1 year of follow-up for clinical outcomes (PFS, OS).
Other outcomes:
measure: Correlation of circulating PD-L1 and exosomal PD-L1 with [18F]AlF-NOTA-PCP2 PET/CT imaging
timeFrame: Pre-treatment, and at follow-up visits (up to 1 year).
Locations:
city: Jinan
country: China
facility: Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences
state: Shandong
Study officials:
affiliation: Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences: Shandong Cancer Hospital and Institute
name: Man Hu, Dr.
role: STUDY_CHAIR
References:
citation: Wang Y, Zhang Y, Chen Y, Wang S, Liu W, Liu Z, Hu M. [18F]AlF-NOTA-PCP2: a novel PET/CT tracer for enhanced PD-L1 heterogeneity imaging and comparative analysis with [18F]AlF-NOTA-WL12 in glioblastoma xenografts. Eur J Nucl Med Mol Imaging. 2024 Sep;51(11):3161-3175. doi: 10.1007/s00259-024-06743-5. Epub 2024 May 7.
citation: Zhang Y, Wang Y, Chen Y, Ding X, Wang S, Liu W, Hu M, Liu Z. PET Imaging of Peptide Probe Al[18F]F-NOTA-PCP1 for Monitoring the Engagement of PD-L1 Antibodies in Tumors. Mol Pharm. 2024 Mar 4;21(3):1515-1525. doi: 10.1021/acs.molpharmaceut.3c01151. Epub 2024 Jan 30.