A Clinical Study of [177Lu]Lu-XT117 Injection in Patients With Advanced Solid Tumors

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

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.

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