Comparing DLL3 PET/CT to Standard Scans in Neuroendocrine Cancer

NCT07733024 | Not Yet Recruiting Phase 2

• 1 other identifier: NEC-DLL3-01
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neuroendocrine Tumors

Keywords

Neuroendocrine Tumors; [⁶⁸Ga]Ga-DLL3 Nanobody; DLL3 expression; Comparative Study

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline (within 14 days of enrollment) and Month 6

Secondary Outcomes (5)

• Lesion Detection Rate

  Baseline (within 14 days of enrollment)

• Clinical Management Change Rate

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

• Safety and Tolerability

  Up to 24 hours post-injection

• Correlation with DLL3 Expression

  At study completion (expected at Month 6)

• Target-to-Background Ratio (TBR)

  Baseline (within 14 days of enrollment)

Other Outcomes (2)

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

  Baseline (within 14 days of enrollment)

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

  Baseline (within 14 days of enrollment) and Month 24

Study Arms (1)

[⁶⁸Ga]Ga-DLL3 Nanobody PET/CT

EXPERIMENTAL

Participants receive a single intravenous injection of \[⁶⁸Ga\]Ga-DLL3 nanobody (a novel radiotracer targeting Delta-like ligand 3 \[DLL3\]), followed by whole-body PET/CT imaging at approximately 2 hours post-injection. DLL3 is a protein aberrantly expressed on the surface of neuroendocrine tumor cells. The nanobody is engineered for high-affinity and specificity binding to DLL3, enabling non-invasive visualization of DLL3-expressing tumor lesions. The total injected protein mass and molar activity are controlled according to the study protocol to ensure consistent imaging quality. PET/CT images are acquired from skull base to mid-thigh (extended to feet if clinically indicated) using a standardized acquisition protocol. Image reconstruction is performed with consistent algorithms across all participants. Each subject serves as their own control, with the DLL3 PET/CT results compared to their conventional imaging (FDG PET/CT or PSMA PET/CT) performed within 2 weeks. The scan is performed

Drug: 68Ga-PFD3

Interventions

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

Also known as: 68Ga-DLL3

[⁶⁸Ga]Ga-DLL3 Nanobody PET/CT

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Life expectancy \> 3 months.
• Voluntarily agrees to participate and provides written informed consent.
• Females of childbearing potential and male participants agree to use reliable contraceptive methods for 6 months after the last study drug administration.
• Willing and able to comply with scheduled visits, diagnostic procedures, clinical laboratory tests, and other study procedures.

You may not qualify if:

• 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).
• Total bilirubin \> 1.5 × ULN.
• Inability to tolerate or cooperate with PET/CT imaging procedures, including but not limited to: severe claustrophobia, inability to remain supine and still for at least 30 minutes, or inability to establish adequate intravenous access.
• Received chemotherapy, biological therapy, endocrine therapy, molecular targeted therapy, or investigational drug therapy within 4 weeks prior to enrollment.
• Currently participating in another interventional clinical trial.
• Prior exposure to any DLL3-targeted therapeutic agent (e.g., Tarlatamab, bispecific T-cell engagers, or DLL3-targeted radioimmunotherapy) or DLL3-targeted radiotracer.
• Prior radionuclide therapy or diagnostic scan with an interval of less than 10 physical half-lives of the administered radionuclide prior to study tracer administration.
• History of any other malignancy within 5 years prior to screening, except for adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or other malignancies with negligible risk of recurrence in the investigator's opinion.
• Clinically significant abnormalities on physical examination, electrocardiogram (ECG), or clinical laboratory tests during screening that, in the investigator's opinion, may compromise safety or study compliance.
• Any other condition that, in the investigator's opinion, makes the patient unsuitable for study participation (e.g., severe psychiatric disorders, substance abuse, poor compliance).

Sponsors & Collaborators

• Tingting Yuan: lead

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Related Publications (3)

• Henke RM, Meredith DM, Borromeo MD, Savage TK, Johnson JE. Ascl1 and Neurog2 form novel complexes and regulate Delta-like3 (Dll3) expression in the neural tube. Dev Biol. 2009 Apr 15;328(2):529-40. doi: 10.1016/j.ydbio.2009.01.007. Epub 2009 Jan 14.

  PMID: 19389376 RESULT

• Tendler S, Dunphy MP, Agee M, O'Donoghue J, Aly RG, Choudhury NJ, Kesner A, Kirov A, Mauguen A, Baine MK, Schoder H, Weber WA, Rekhtman N, Lyashchenko SK, Bodei L, Morris MJ, Lewis JS, Rudin CM, Poirier JT. Imaging with [89Zr]Zr-DFO-SC16.56 anti-DLL3 antibody in patients with high-grade neuroendocrine tumours of the lung and prostate: a phase 1/2, first-in-human trial. Lancet Oncol. 2024 Aug;25(8):1015-1024. doi: 10.1016/S1470-2045(24)00249-3. Epub 2024 Jun 28.

  PMID: 38950555 RESULT

• Lahiri A, Maji A, Potdar PD, Singh N, Parikh P, Bisht B, Mukherjee A, Paul MK. Lung cancer immunotherapy: progress, pitfalls, and promises. Mol Cancer. 2023 Feb 21;22(1):40. doi: 10.1186/s12943-023-01740-y.

  PMID: 36810079 RESULT

MeSH Terms

Conditions

Neuroendocrine Tumors

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Central Study Contacts

Tingting Yuan, MD

CONTACT

+86 13051707479; biluohtt@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Postdoctoral Fellow; Attending Physician

Study Record Dates

• First Submitted: July 13, 2026
• First Posted: July 29, 2026
• Study Start: July 6, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 29, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)