Safety Trial of 68Ga/177Lu-NRT6020 in FAP-Positive Advanced Solid Tumor Patients

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

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.

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.

Key Inclusion Criteria:

1. Male or female participants aged 18-80;
2. 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);
3. Have at least one measurable lesion as per RECIST v1.1/PERCIST criteria;
4. For stage 2 and stage 3, a positive 68Ga-NRT6020 Injection PET/CT imaging results is required;
5. Participants must have adequate organ function;
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Life expectancy ≥3 months;
8. 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.

Key Exclusion Criteria:

1. Known allergy to 68Ga-NRT6020 Injection, 177Lu-NRT6020 Injection, or any of their ingredients, such as alcohol;
2. Presence or suspicion of primary central nervous system tumors or intracranial metastasis;
3. 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.;
4. 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;
5. Presence of severe or uncontrolled cardiac diseases requiring treatment;
6. High risk of bleeding;
7. Active syphilis or human immunodeficiency virus (HIV) antibody positive;
8. HBsAg-positive or HBcAb-positive with HBV-DNA levels above the detection limit;
9. Failure to alleviate previous antitumor treatment toxicities to Grade 0 or 1 according to CTCAE v5.0;
10. Participate in any other clinical trials within 1 month before the first dosing of 68Ga-NRT6020 Injection.