A Phase 1 Clinical Trial to Evaluate the Safety and Tolerability of 68Ga-NRT6020 Injection and 177Lu-NRT6020 Injection in FAP-Positive Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 132
- 试验地点
- 2
- 主要终点
- RP2D for 177Lu-NRT6020 Injection (stage 3)
研究概览
简要总结
Stage 1 (Safety study for 68Ga-NRT6020 Injection):
The goal of this clinical trial stage is to evaluate the safety of 68Ga-NRT6020 Injection in participants with advanced solid tumors. The study will also assess the biodistribution, radiation dosimetry, imaging profile, and pharmacokinetics of the drug. Additionally, researchers aim to investigate how consistent the PET/CT imaging results of 68Ga-NRT6020 are with 18F-FDG PET/CT imaging and FAP immunohistochemistry (IHC) results.
Stage 2 (Safety and tolerability study for 177Lu-NRT6020 Injection):
This stage focuses on evaluating the safety and tolerability of 177Lu-NRT6020 Injection in FAP-positive participants with advanced solid tumors. Researchers will also assess the safety of 68Ga-NRT6020 Injection in this population. The study will evaluate the biodistribution, radiation dosimetry, pharmacokinetics, and preliminary efficacy of 177Lu-NRT6020 Injection. Additionally, the imaging profile of 68Ga-NRT6020 and its consistency with other imaging techniques will be further investigated.
Stage 3 (Preliminary efficacy study for 68Ga/177Lu-NRT6020 Injection):
The objective of this stage is to evaluate the safety of 177Lu-NRT6020 Injection and 68Ga-NRT6020 Injection in FAP-positive participants with advanced solid tumors, as well as to determine the recommended phase 2 dose (RP2D) of 177Lu-NRT6020 Injection. The study will also assess the preliminary efficacy, biodistribution, radiation dosimetry, and pharmacokinetics of the drugs. Furthermore, researchers will investigate the imaging profile of 68Ga-NRT6020 and its consistency with other imaging techniques.
详细描述
During the study, 68Ga-NRT6020 served as the companion diagnostic agent for 177Lu-NRT6020 to select eligible patients. This stage 2 and stage 3 of the study is designed as a multi-center, multiple-dose, parallel-cohort study, and will enroll FAP-positive (FAP-positive is defined by positive PET/CT imaging results for 68Ga-NRT6020; and dose of 68Ga-NRT6020 will be confirmed by the SRC after stage 1) patients with advanced solid tumors who have failed or have no available standard therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants aged 18-80;
- •Histologically or cytologically confirmed advanced solid tumors; advanced solid tumors patients who have failed prior standard therapies or deemed unsuitable for standard therapies (only for stage 2 and stage 3);
- •Have at least one measurable lesion as per RECIST v1.1/PERCIST criteria;
- •For stage 2 and stage 3, a positive 68Ga-NRT6020 Injection PET/CT imaging results is required;
- •Participants must have adequate organ function;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy ≥3 months;
- •For women of childbearing potential, a negative blood pregnancy test within 3 days before the first dose is required, and fertile male and female participants of childbearing potential must agree to use effective contraception with their partners from the signing of the informed consent form until 12 months after the last dose of the investigational drug.
排除标准
- •Known allergy to 68Ga-NRT6020 Injection, 177Lu-NRT6020 Injection, or any of their ingredients, such as alcohol;
- •Presence or suspicion of primary central nervous system tumors or intracranial metastasis;
- •For stage 1: Received prior antitumor treatments within 7 days before the investigational drug dosing, and/or plan to receive antitumor treatments during the safety observation period; For stage 2 and stage 3: Received prior antitumor treatments within 4 weeks before the initial investigational drug dosing, including chemotherapy, radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy, etc.;
- •History of other malignancies within 5 years prior to the first dose of the investigational drug, excluding cured non-melanoma skin cancer, early-stage papillary thyroid cancer, and cervical carcinoma in situ;
- •Presence of severe or uncontrolled cardiac diseases requiring treatment;
- •High risk of bleeding;
- •Active syphilis or human immunodeficiency virus (HIV) antibody positive;
- •HBsAg-positive or HBcAb-positive with HBV-DNA levels above the detection limit;
- •Failure to alleviate previous antitumor treatment toxicities to Grade 0 or 1 according to CTCAE v5.0;
- •Participate in any other clinical trials within 1 month before the first dosing of 68Ga-NRT6020 Injection.
研究组 & 干预措施
68Ga-NRT6020 Injection (stage 1)
Stage 1 is designed as a single-arm, single-dose study, planning to enroll participants with advanced solid tumors, with two planned dose groups: a low-dose group and a high-dose group. The dose groups are sequentially enrolled from low to high, with 6 participants planned for enrollment in each dose group.
干预措施: 68Ga-NRT6020 Injection (Diagnostic Test)
68Ga-NRT6020 Injection+ 177Lu-NRT6020 Injection (stage 2)
Stage 2 is designed as a single-arm, multiple-dose, "3+3" dose-escalation study, and will enroll FAP-positive patients with advanced solid tumors who have failed or have no available standard therapy.
干预措施: 68Ga-NRT6020 Injection (Diagnostic Test)
68Ga-NRT6020 Injection+ 177Lu-NRT6020 Injection (stage 2)
Stage 2 is designed as a single-arm, multiple-dose, "3+3" dose-escalation study, and will enroll FAP-positive patients with advanced solid tumors who have failed or have no available standard therapy.
干预措施: 177Lu-NRT6020 Injection (stage 2) (Drug)
68Ga-NRT6020 Injection+ 177Lu-NRT6020 Injection (stage 3)
This stage 3 of the study is designed as a multi-center, single-arm, multiple-dose, parallel-cohort study, and will enroll FAP-positive patients with advanced solid tumors who have failed or have no available standard therapy.
干预措施: 68Ga-NRT6020 Injection (Diagnostic Test)
68Ga-NRT6020 Injection+ 177Lu-NRT6020 Injection (stage 3)
This stage 3 of the study is designed as a multi-center, single-arm, multiple-dose, parallel-cohort study, and will enroll FAP-positive patients with advanced solid tumors who have failed or have no available standard therapy.
干预措施: 177Lu-NRT6020 Injection (stage 3) (Drug)
结局指标
主要结局
RP2D for 177Lu-NRT6020 Injection (stage 3)
时间窗: Through study completion, an average of 1 year
Determine the optimal dose of 177Lu-NRT6020
Adverse events
时间窗: Through study completion, an average of 1 year
Occurrence of adverse events
Dose-limiting toxicity (DLT) (stage 2)
时间窗: After the first dose of 177Lu-NRT6020 administration, up to 42 days
Evaluate the safety and tolerability of 177Lu-NRT6020
Maximum tolerated dose (MTD) (if any) or recommended dose for expansion study of 177Lu-NRT6020 Injection (stage 2)
时间窗: Through study completion, an average of 1 year
Evaluating the safety and tolerability of 177Lu-NRT6020 with the aim of determining the optimal dose
次要结局
- Standardized uptake values (SUV) (stage 1)(After the administration of 68Ga-NRT6020, within 24 hours)
- Radioactivity in biological specimen (stage 1)(After the administration of 68Ga-NRT6020, within 24 hours)
- Time to reach maximum concentration (Tmax) of 68Ga-NRT6020 (stage 1)(After the administration of 68Ga-NRT6020, within 24 hours)
- Effective dose (stage 1)(After the administration of 68Ga-NRT6020, within 24 hours)
- Peak Plasma Concentration (Cmax) of 68Ga-NRT6020 (stage 1)(After the administration of 68Ga-NRT6020, within 24 hours)
- Area under the plasma concentration versus time curve (AUC) of 68Ga-NRT6020 Injection (stage 1)(After the administration of 68Ga-NRT6020, within 24 hours)
- Half life (t1/2) of 68Ga-NRT6020 (stage 1)(After the administration of 68Ga-NRT6020, within 24 hours)
- Progression-free survival (PFS) (stage 3)(After the administration of 177Lu-NRT6020, within 1 year)
- Scanning time window (stage 1)(After the administration of 68Ga-NRT6020, within 3 hours)
- Standardized uptake values (SUV) (stage 2 and stage 3)(After the administration of 177Lu-NRT6020, at least 7 days)
- Absorbed dose (stage 1)(After the administration of 68Ga-NRT6020, within 24 hours)
- Absorbed dose (stage 2 and stage 3)(After the administration of 177Lu-NRT6020, at least 7 days)
- Effective dose (stage 2 and stage 3)(After the administration of 177Lu-NRT6020, at least 7 days)
- Objective response rate (ORR) (stage 2 and stage 3)(After the administration of 177Lu-NRT6020, within 1 year)
- Duration of response (DOR) (stage 2 and stage 3)(After the administration of 177Lu-NRT6020, within 1 year)
- Progression-free survival (PFS) (stage 2 and stage 3)(After the administration of 177Lu-NRT6020, within 1 year)
- Radioactivity in biological specimen (stage 2)(After the administration of 177Lu-NRT6020, at least 7 days)
- Peak Plasma Concentration (Cmax) of 177Lu-NRT6020 (stage 2 and stage 3)(After the administration of 177Lu-NRT6020, at least 7 days)
- Time to reach maximum concentration (Tmax) of 177Lu-NRT6020 (stage 2 and stage 3)(After the administration of 177Lu-NRT6020, at least 7 days)
- Area under the plasma concentration versus time curve (AUC) of 177Lu-NRT6020 (stage 2 and stage 3)(After the administration of 177Lu-NRT6020, at least 7 days)
- Half life (t1/2) of 177Lu-NRT6020 (stage 2 and stage 3)(After the administration of 177Lu-NRT6020, at least 7 days)
- Objective response rate (ORR) (stage 3)(After the administration of 177Lu-NRT6020, within 1 year)
- Duration of response (DOR) (stage 3)(After the administration of 177Lu-NRT6020, within 1 year)