A Clinical Study to Evaluate the Safety, Tolerability, Dosimetry and Preliminary Efficacy of [177Lu]Lu-XT117 Injection in FAP-positive Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Recommended Phase 2 Dose (RP2D)
研究概览
简要总结
This is a single-center, single-arm clinical study to evaluate the safety, tolerability, dosimetry and preliminary efficacy of [177Lu]Lu-XT117 injection in patients with FAP-positive advanced solid tumors. Dose escalation will be conducted to determine the Dose Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD), Recommended Phase 2 Dose (RP2D), and to assess dosimetry characteristics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years old
- •Eastern Cooperative Oncology Group (ECOG) Performance status 0 to 1
- •Confirmed as malignant solid tumor by histopathology
- •Have measurable lesions based on RECIST 1.1
- •Have failed standard treatment (disease progression or intolerance) or lack of standard treatment
- •Positive FAP expression confirmed by FAP PET/CT
- •Sufficient bone marrow capacity and organ function
排除标准
- •High intensity and large amounts of off-target uptake detected by FAP molecular imaging, and were assessed as inappropriate for [177Lu]Lu-XT117 therapy by the investigators
- •Previous systemic antitumor therapy (including prior chemotherapy, radiotherapy, immunotherapy, and other investigational drugs) ≤28 days before receiving study therapy; previous treatment with Chinese medicine with anti-tumor indications within 2 weeks before receiving study therapy
- •Uncontrolled diabetes, with baseline fasting blood glucose > 2×ULN
- •Clinically significant serious cardiovascular disease, including but not limited to: a. >Grade II congestive heart failure as per New York Heart Association (NYHA) ; b. Unstable angina pectoris or myocardial infarction within 6 months before the first administration of the study drug; c. Severe arrhythmia within 6 months prior to the first administration; d. Poorly controlled hypertension (patients who keep the blood pressure to ≤ Grade 2 hypertension [CTCAE5.0] with hypotensors are acceptable for enrollment); e. QTc>450 ms (male) or 470 ms (female), congenital prolonged QT syndrome, and use of medications that prolong QT
- •Clinically serious thromboembolic disease within 6 months prior to the first administration of the study drug
- •Major surgery within 4 weeks prior to the first administration
- •History of severe gastrointestinal ulcers or perforations or history of intestinal obstruction within 6 months prior to the first administration
- •Active infection requiring systemic treatment (oral or intravenous administration) within 2 weeks prior to the first administration, except for topical treatment
- •History of non-infectious interstitial lung disease (ILD), such as idiopathic pulmonary fibrosis, idiopathic interstitial pneumonia, pneumoconiosis, and drug-related interstitial pneumonia, or severe impairment of lung function
- •Had other malignancies within 5 years prior to screening (except clinically cured early stage malignancies)
- •Primary central nervous system (CNS) tumor or symptomatic CNS metastasis, expect:
- •Subjects with asymptomatic brain metastases;
- •Subjects whose CNS lesions were stable for ≥4 weeks after local treatment and who stopped glucocorticoid or anticonvulsant therapy at least 2 weeks prior to study drug administration could be enrolled;
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage
研究组 & 干预措施
[177Lu]Lu-XT117 dose escalation
干预措施: [177Lu]Lu-XT117 (Drug)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D)
时间窗: Through study completion, assessed up to 2 years
RP2D will be determined on the basis of data indicating adequate tolerability and therapeutic effectiveness, and appropriate dosimestry. RP2D may be at or below the MTD.
Treatment emergent adverse events
时间窗: Until 6 months after the last administration
Incidence and severity of treatment emergent adverse events will be assessed as per CTCAE v5.0).
Dose-limiting toxicities (DLTs) during the DLT evaluation period
时间窗: Up to 6 weeks after the first administration
A DLT is defined as any drug-related toxicity that fulfills certain criteria predescribed in the study protocol.
Maximum tolerated dose (MTD)
时间窗: Up to 6 weeks after the first administration
MTD will be determined by 3+3 dose escalation design.
次要结局
- Duration of Response (DOR)(Every 6 weeks after first administration until disease progression or death or through study completion, assessed up to 2 years)
- Disease Control Rate (DCR)(Every 6 weeks after first administration until disease progression or through study completion, assessed up to 2 years)
- Progression Free Survival (PFS)(Every 6 weeks after first administration until disease progression or death or through study completion, assessed up to 2 years)
- Overall Response Rate (ORR)(Every 6 weeks after first administration until disease progression or through study completion, assessed up to 2 years)
- Overall Survival (OS)(Every 6 weeks after first administration until death, assessed up to 2 years)
- Radiation dosimetry of [177Lu]Lu-XT117 to whole body, lesions, organs, and selected regions of interest(1、4、24、48、72 and 168 hours after first administration)
研究者
Ruimin Wang
Chief of Nuclear Medicine Department
Chinese PLA General Hospital