Comparing DLL3 PET/CT to Standard Scans in Neuroendocrine Cancer

ConditionNeuroendocrine Tumors

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18-80

SponsorTingting Yuan

About this trial

This study is testing a new PET/CT scan that uses a special tracer called \[⁶⁸Ga\]Ga-DLL3 nanobody to see if it can better detect cancer spread (metastases) in people with neuroendocrine tumors than the standard scans currently used (FDG PET/CT or PSMA PET/CT). DLL3 is a protein found on the surface of many neuroendocrine tumor cells, and the new tracer is designed to stick to this protein, making tumors visible on the scan. The goal is to find out whether this new imaging method can give doctors more accurate information about where the cancer has spread and help them choose the most appropriate treatment for each patient.

The study is prospective, multi-center, and self-controlled, meaning each participant will receive both the new scan and the standard scan, allowing a direct side-by-side comparison in the same person. Depending on the type of neuroendocrine tumor, participants will be assigned to one of two groups: one group will be compared with FDG PET/CT and the other with PSMA PET/CT. The two scans will be performed within two weeks of each other, and all images will be read by independent experts who do not know the patient's clinical history, to ensure objective and unbiased results.

The investigators plan to enroll about 180-200 patients aged 18 or older who have confirmed neuroendocrine tumors with at least two metastatic sites. The total duration of participation is approximately 6 months, consisting of a screening period of up to 14 days, two imaging scans completed within 2 days, and a final follow-up visit at 6 months to evaluate participants' health and disease progression. Participation is entirely voluntary, and participants may withdraw at any time without affecting participants' standard medical care.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 18 and ≤ 80 years at the time of signing the informed consent form, male or female.

Histologically or cytologically confirmed neuroendocrine neoplasms (NENs), including but not limited to small cell lung cancer (SCLC), neuroendocrine prostate cancer (NEPC), gastroenteropancreatic neuroendocrine tumors (GEP-NENs), or other NEN subtypes.

Patients with strong clinical and radiological suspicion of NENs based on imaging (CT/MRI/conventional PET/CT) and clinical presentation.

At least 2 evaluable metastatic lesions (multiple metastases) confirmed by conventional imaging (CT/MRI/PET/CT).

Disqualifiers

Known severe immediate-type hypersensitivity or anaphylactic reaction to DLL3-targeted tracers, nanobody proteins, chelators, buffer components, or excipients.

Pregnant or breastfeeding women.

Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m².

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN).

Trial design

Design model

Single group

Treatments tested in this trial

68Ga-PFD3
Drug
\[⁶⁸Ga\]Ga-PFD3 is a novel PET tracer constructed by conjugating a DLL3-specific nanobody (single-domain antibody, \~15 kDa) with a chelator for ⁶⁸Ga radiolabeling. DLL3 (Delta-like ligand 3) is a cell-surface protein that is rarely expressed in healthy adult tissues but is overexpressed in over 80% of small cell lung cancer and in other high-grade neuroendocrine tumors, making it an attractive target for molecular imaging. The nanobody platform offers advantages over conventional monoclonal antibody-based tracers (e.g., \[⁸⁹Zr\]Zr-DFO-SC16.56): smaller size (\~15 kDa vs. \~150 kDa) enables superior tissue penetration, rapid blood clearance, and shorter in vivo residence time, allowing same-day PET/CT imaging within hours post-injection. Participants receive a single intravenous injection of \[⁶⁸Ga\]Ga-PFD3 (activity: 111-185 MBq; protein mass and molar activity controlled per protocol), followed by whole-body PET/CT acquisition at approximately 2 hours post-injection. Images are acquired from

Treatment groups

200 Participants

are divided into 1 treatment group

Group A: [⁶⁸Ga]Ga-DLL3 Nanobody PET/CTExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Diagnostic Accuracy of [⁶⁸Ga]Ga-DLL3 Nanobody PET/CT in Detecting Metastatic Lesions

Sensitivity and specificity of \[⁶⁸Ga\]Ga-DLL3 nanobody PET/CT for detecting metastatic lesions in patients with neuroendocrine neoplasms, using a composite reference standard (incorporating histopathology, conventional imaging \[FDG/PSMA PET/CT, diagnostic CT/MRI\], and 6-month clinical/imaging follow-up) as the truth standard.

Time frame

Baseline (within 14 days of enrollment) and Month 6

Secondary outcomes

Lesion Detection Rate

Per-lesion detection rate of \[⁶⁸Ga\]Ga-DLL3 PET/CT compared to FDG or PSMA PET/CT, stratified by anatomical location (e.g., liver, bone, lung, brain, lymph nodes).

Time frame

Baseline (within 14 days of enrollment)

Clinical Management Change Rate

Proportion of patients whose clinical management (e.g., staging, treatment selection, or biopsy site decision) is altered based on \[⁶⁸Ga\]Ga-DLL3 PET/CT results compared to conventional imaging.

Time frame

Baseline (at time of image interpretation, within 14 days of enrollment)

Safety and Tolerability

Incidence, severity, and causality of adverse events (graded per CTCAE v5.0) following single intravenous injection of \[⁶⁸Ga\]Ga-DLL3 nanobody, including injection site reactions, allergic reactions, and any serious adverse events.

Time frame

Up to 24 hours post-injection

Correlation with DLL3 Expression

Correlation between \[⁶⁸Ga\]Ga-DLL3 PET/CT uptake (SUVmax, SUVmean) and DLL3 expression level by immunohistochemistry (IHC) in biopsied tumor specimens (where available).

Time frame

At study completion (expected at Month 6)

Other outcomes

Baseline SUVmax of [⁶⁸Ga]Ga-DLL3 PET/CT as a Predictor of Clinical Benefit

The maximum standardized uptake value (SUVmax) derived from baseline \[⁶⁸Ga\]Ga-DLL3 nanobody PET/CT imaging, measured within 14 days prior to enrollment. The optimal cut-off value for SUVmax will be determined using receiver operating characteristic (ROC) curve analysis to stratify patients into high- vs. low-expression groups. This individual parameter will be evaluated for its ability to predict objective response or progression-free survival benefit from DLL3-targeted therapies (e.g., Tarlatamab).

Time frame

Baseline (within 14 days of enrollment)

Hazard Ratio (HR) for 24-Month Overall Survival Based on Baseline SUVmax Cut-off

The hazard ratio (HR) with 95% confidence interval, derived from univariate Cox proportional hazards regression, comparing 24-month overall survival between neuroendocrine neoplasm patients stratified by the optimal baseline \[⁶⁸Ga\]Ga-DLL3 nanobody PET/CT SUVmax cut-off value (high-expression vs. low-expression groups). Overall survival is measured as time (in months) from enrollment to death from any cause.

Time frame

Baseline (within 14 days of enrollment) and Month 24

Sponsors and contacts

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Tingting Yuan

Lead sponsor

Peking University First Hospital

Sponsor institution

Source ClinicalTrials.gov

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