Clinical trial NCT05410743: Evaluation of 177Lu-TATE-EB-01（LNC1010）in SSTR2-positive Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: SSTR2-positive Tumors
Keywords: SSTR2-positive tumors
177Lu
LNC1010
SSTR antagonist
Lead sponsor: The First Affiliated Hospital of Xiamen University
Sponsor class: OTHER
First posted: 2022-06-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: phase 1 To evaluate response to the different groups with doses of 2.22 GBq(60 mCi) and 3.33GBq (90 mCi) and 4.99 GBq (135mCi) of 177Lu-LNC1010 in patients with advanced or metastatic SSTR2-positive tumors;Phase 2 will reassess treatment efficacy and safety using a fixed dose identified in Phase 1.
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or older;
* Histologically proven or cytologically confirmed SSTR positive cancers;
* Measurable disease as defined by Response Criteria in Solid Tumors (RECIST) version 1.1;
* Overexpression of somatostatin receptors of the target lesions at 68Ga-DOTA-TATE positron emission tomography (PET)/computed tomography (CT) with standard uptake value(SUV) of lesions greater than normal liver in at least 1 lesion;
* Patients who were able to provide informed consent (signed by participant, parent or legal representative) and assent according to the guidelines of the Clinical Research Ethics Committee.

Exclusion Criteria:

* Women who are pregnant or breastfeeding;
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-EB-TATE as assessed from medical records;
* Previous radioligand treatment with 177Lu-DOTA-TATE;
* Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 4 weeks or 4 half-lives whichever is longer, before the first administration of study drug;
* Participant has not fully recovered from major surgery or significant traumatic injury prior the first dose of study drug or expects to have major surgery during the study period or within 3 months after the last dose of study drug;
* Life expectancy \< 3 months as assessed by the treating physician;
* Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements;
* The inability or unwillingness of the research participant, parent or legal representative to provide written informed consent.

Primary outcomes:
measure: Phase 1-Incidence of treatment-related adverse events (safety and tolerability)
timeFrame: At the end of Cycle 2 (each cycle is 56 days)
measure: Phase 2-Efficacy
timeFrame: At the end of Cycle 4 (each cycle is 56 days)
Secondary outcomes:
measure: Phase-1 Dosimetry
timeFrame: At the end of Cycle 1 (each cycle is 56 days)
measure: Phase 1-Overall response rate (ORR)
timeFrame: At the end of Cycle 2 (each cycle is 56 days)
measure: Phase-2 Progression-free survival
timeFrame: baseline, every 8 weeks up to 1 year after last patient first treatment
Other outcomes:
Locations:
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
Study officials:
References:
citation: Zhu W, Cheng Y, Jia R, Zhao H, Bai C, Xu J, Yao S, Huo L. A Prospective, Randomized, Double-Blind Study to Evaluate the Safety, Biodistribution, and Dosimetry of 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3 in Patients with Well-Differentiated Neuroendocrine Tumors. J Nucl Med. 2021 Oct;62(10):1398-1405. doi: 10.2967/jnumed.120.253096. Epub 2021 Feb 12.