Evaluation of [⁶⁸Ga/¹⁷⁷Lu]HT547: Safety, Biodistribution, and Dosimetry in Solid Tumors

Official title

Evaluation of the Safety, Biodistribution and Human Dosimetry of [68Ga]Ga-HT547 PET/CT and [177Lu]Lu-HT547 SPECT/CT in the Clinical Diagnosis of Solid Tumor Patients

Overview

Urokinase plasminogen activator receptor (uPAR), the cell-surface receptor for its ligand uPA, plays a critical role in regulating cell migration and invasion-key drivers of cancer progression. This study aims to evaluate a novel uPAR-targeting radiopharmaceutical pair: the diagnostic agent \[⁶⁸Ga\]Ga-HT547 and the therapeutic agent \[¹⁷⁷Lu\]Lu-HT547. In patients with breast cancer, head and neck cancer, pancreatic cancer, or glioma, we will assess the diagnostic performance and biodistribution of these tracers using \[⁶⁸Ga\]Ga-HT547 and \[¹⁷⁷Lu\]Lu-HT547 SPECT/CT.

Interventions

• Drug [⁶⁸Ga]Ga-HT547 and [¹⁷⁷Lu]Lu-HT547
  All enrolled participants will undergo the same intervention procedure: first, a single intravenous dose (approximately 150 MBq) of ⁶⁸Ga-HT547 for uPAR-targeted PET/CT diagnostic imaging. Subsequently, a single intravenous dose (approximately 4 GBq) of ¹⁷⁷Lu-HT547 will be administered for follow-up SPECT/CT imaging and dosimetry studies.

Primary outcome measures

• Diagnostic efficacy [Time frame: Screening, Day 1 post-⁶⁸Ga-HT547, Day 1, 3, 5, 7 post-¹⁷⁷Lu-HT547]

Eligibility criteria

Inclusion criteria

• Willing and able to communicate with the investigator, understand and comply with trial requirements, voluntarily participate in the trial, and provide written informed consent.
• Aged 18 years or older, regardless of gender.
• Expected survival of at least 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Patients with solid tumors (breast cancer, head and neck cancer, pancreatic cancer, or brain glioma) confirmed by histology or cytology.
• Radiographic evidence of disease progression within 12 months prior to screening (according to RECIST 1.1 criteria).
• At least one measurable target lesion according to RECIST 1.1 criteria.
• Positive uptake in the target lesion on ⁶⁸Ga-HT547 Positron Emission Tomography (PET) scan, with SUV ≥ 4.
• Recovery from toxicities related to prior therapy to ≤ Grade 1 or baseline (except for alopecia, vitiligo, etc.).
• For subjects of childbearing potential: Agreement to remain abstinent or use effective contraception (including intrauterine devices, etc.) from signing the ICF until at least 24 weeks after the last dose.

Exclusion criteria

• Pregnant or breastfeeding women, or women with a positive baseline pregnancy test.
• History of severe allergic reaction to any component of the investigational drug injection.
• Received blood transfusion within 4 weeks prior to screening to meet the enrollment criteria.
• Received immunotherapy, chemotherapy, radiotherapy, or other anti-tumor therapy within 4 weeks prior to the first dose.
• Received any investigational drug within 28 days prior to the first dose, or concurrent participation in another clinical study (except: participation in an observational, non-interventional study, or being in the follow-up phase of an interventional study).
• History of other known malignancies within the past 5 years.
• Presence of symptomatic or unstable third-space effusions (e.g., pleural effusion, ascites, pericardial effusion) requiring repeated drainage.
• Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
• Inadequate organ function (meeting any of the following):

• Bone marrow reserve: Neutrophil count < 1.5 x 10⁹/L, or platelet count < 100 x 10⁹/L, or hemoglobin < 90 g/L.
• Liver function: AST/ALT > 3 x ULN (> 5 x ULN for subjects with liver metastases), or albumin ≤ 2.8 g/dL, or total bilirubin > 1.5 x ULN.
• Renal function: Serum creatinine > 1.5 x ULN and creatinine clearance < 60 mL/min (calculated by Cockcroft-Gault formula).
• Severe cardiovascular clinical diseases or symptoms that may increase subject safety risk, including:

• Congestive heart failure (New York Heart Association \[NYHA\] class > II) within the past year.
• Unstable angina within the past year.
• Myocardial infarction within the past year.
• Clinically significant malignant arrhythmia (except for atrial fibrillation, paroxysmal supraventricular tachycardia).
• Presence of clinically significant QTcF prolongation (QTcF > 470 ms, calculated by Fridericia's formula).
• Clinically significant bleeding (e.g., gastrointestinal bleeding, intracranial hemorrhage) within 14 days prior to the first dose.
• Major surgery or significant trauma within 28 days prior to the first dose.
• Any other condition that, in the investigator's judgment, may increase safety risk or interfere with its interpretation.
• Inability of the subject to understand and comply with study instructions and requirements.
• Any other situation deemed inappropriate by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07639970 · 2026-0308-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗