A Phase 1, Non-Randomized, Open-Label, Dose Escalation, Single-Center Study to Determine the Safety, Bio-distribution, and Preliminary Effectiveness of 177Lu-TATE-EB-01（LNC1010）in Adult Subjects With SSTR2-positive Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Phase 1-Incidence of treatment-related adverse events (safety and tolerability)
研究概览
简要总结
177Lu-LNC1010(177Lu-EB-TATE-01) is a radiotherapeutic drug indicated in subjects with unresectable, metastatic somatostatin receptor (SSTR) positive neuroendocrine tumors (NETs).
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), 3.7GBq (100mCi) and 5.18GBq (140mCi) of 177Lu-LNC1010 will be injected intravenously. All patients will undergo 68Ga-DOTA-Octreotide(TATE) PET/CT scans before and after the treatment.
详细描述
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 study was designed to evaluate the efficacy of a long-lasting radiolabeled somatostatin analogue 177Lu-LNC1010 in patients with SSTR2-positive tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 years or older;
- •Histologically proven or cytologically confirmed, inoperable, NPC, and 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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: 177Lu-LNC1010 1 (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.
干预措施: 177Lu-LNC1010 2 (Drug)
177Lu-LNC1010 3
The patients were intravenously injected with single dose 4.99 GBq (135mCi) of 177Lu-LNC1010 and underwent 68Ga-DOTA-TATE PET/CT scans before and after the treatment.
干预措施: 177Lu-LNC1010 3 (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.
干预措施: 177Lu-LNC1010 4 (Drug)
结局指标
主要结局
Phase 1-Incidence of treatment-related adverse events (safety and tolerability)
时间窗: At the end of Cycle 2 (each cycle is 56 days)
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.Dose-limiting toxicity was defined as any 177Lu-DOTA-EB-FAPI-related AE ≥ grade 3 (G3). For Hemoglobin \< 8.0 g/dL; \< 4.9 mmol/L; \< 80 g/L; Need blood transfusion heal. Severe hypocytosis or with this age group The total number of normal cells was reduced \>50% and ≤75%.
Phase 2-Efficacy
时间窗: At the end of Cycle 4 (each cycle is 56 days)
Patients received a single, fixed dose of 177Lu-LNC1010 via intravenous injection, utilizing the well-tolerated and safe dose identified in Phase 1.68Ga-DOTATATE will be performed for efficacy evaluation by RECIST 1.1. Particularly, 68Ga-DOTATATE will be performed at baseline, and 8 weeks after two treatment cycles.
次要结局
- Phase-1 Dosimetry(At the end of Cycle 1 (each cycle is 56 days))
- Phase 1-Overall response rate (ORR)(At the end of Cycle 2 (each cycle is 56 days))
- Phase-2 Progression-free survival(baseline, every 8 weeks up to 1 year after last patient first treatment)