NCT05410743

Evaluation of 177Lu-TATE-EB-01（LNC1010）in SSTR2-positive Tumors

A Phase 1/2, Non-Randomized, Open-Label, Dose Escalation, Single-Center Study to Determine the Safety, Bio-distribution, and Preliminary Effectiveness and Efficacy of 177Lu-TATE-EB-01（LNC1010）in Adult Subjects With SSTR2-positive Tumors

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: The First Affiliated Hospital of Xiamen University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

177Lu-LNC1010(177Lu-EB-TATE-01) is a radiotherapeutic drug indicated in subjects with unresectable, metastatic somatostatin receptor (SSTR) positive tumors. In this study, we designed and developed a new radioligand, EB-TATE-01 (second generation long-acting EB-TATE formula), through combining EB and altering the linker to further improve the pharmacokinetics and pharmacodynamics, leading to substantially enhanced radioligand therapy effect. This is an open-label, non-controlled, non-randomized study to investigate the long-lasting radiolabeled somatostatin analogue based peptide receptor radionuclide therapy and evaluate response to 177Lu-LNC1010 in patients with advanced SSTR2-positive tumors. Different groups with doses of 2.22GBq (60 mCi), 3.33GBq (90mCi) and 4.99GBq (145mCi) of 177Lu-LNC1010 will be injected intravenously. All patients will undergo 68Ga-DOTA-Octreotide(TATE) PET/CT scans before and after the treatment.

Detailed description

Somatostatin receptor(SSTR), especially SSTR subtype 2 (SSTR2),has been a popular target for molecular imaging and radionuclide therapy in recent years. SSTR antagonists, such as LNC1010, have emerged as a new type of somatostatin analog, characterized by a low internalization rate and high tumor affinity. 68Ga-DOTA(68Ga-DOTA)-LNC1010 has been reported that it showed favorable biodistribution, high tumor uptake, and good tumor retention, resulting in high image contrast. SSTR2 has been found highly expressed in SSTR2-positive tumors, indicating the feasibility of Positron Emission Tomography（PET)/ CT with 68Ga-DOTA-conjugated peptides for imaging SSTR2 expression and peptide-receptor radionuclide therapy (PRRT) for the treatment option in SSTR2-positive tumors. However, a major problem in the therapeutic use of 177Lu-DOTA(177Lu-DOTA)-LNC1010 has been its short half-life and fast rate of clearance. This combined phase 1/2 clinical trial is designed to initially investigate the safety, tolerability, pharmacokinetics, dosimetry, and preliminary efficacy of 177Lu-LNC1010 in patients with advanced or metastatic SSTR2-positive tumors during the phase 1 portion. The objective is to establish a well-tolerated dose with acceptable side effects. Following this, the phase 2 portion of the trial will involve repeated administration of 177Lu-LNC1010 PRRT at the identified safe fixed dose, aiming to maximize the treatment effect while ensuring patient safety. This phase is set to rigorously evaluate the therapeutic efficacy and potential toxicity of 177Lu-LNC1010 in the management of advanced or metastatic SSTR2-positive tumors.

Conditions

• SSTR2-positive Tumors

Interventions

Type	Name	Description
DRUG	177Lu-LNC1010 1	The patients were intravenously injected with single dose 2.22GBq (60 mCi) of 177Lu-LNC1010 and underwent 68Ga-DOTA-TATE PET/CT scans before and after the treatment.
DRUG	177Lu-LNC1010 2	The patients were intravenously injected with single dose 3.33GBq （90 mCi) of 177Lu-LNC1010 and underwent 68Ga-DOTA-TATE PET/CT scans before and after the treatment.
DRUG	177Lu-LNC1010 3	The patients were intravenously injected with single dose 4.99GBq (135 mCi) of 177Lu-LNC1010 and underwent 68Ga-DOTA-TATE PET/CT scans before and after the treatment.
DRUG	177Lu-LNC1010 4	Patients received a single, fixed dose of 177Lu-LNC1010 via intravenous injection, utilizing the well-tolerated and safe dose identified in Phase 1. They also underwent 68Ga-DOTA-TATE PET/CT scans both before and after the treatment to monitor their response.

Timeline

• Start date: 2022-06-01
• Primary completion: 2025-03-24
• Completion: 2025-03-24
• First posted: 2022-06-08
• Last updated: 2025-03-25

Locations

1 site across 1 country: China