a clinical study of [177lu]lu-xt117 injection in patients with advanced solid tumors

Conditions: Advanced Solid Tumor

Summary: 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.


Eligibility criteria:
key inclusion criteria: * ≥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 key exclusion criteria: * 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