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

Official title

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

Overview

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.

Interventions

• Drug [177Lu]Lu-XT117
  \[177Lu\]Lu-XT117 is a radiopharmaceutical therapy in which an beta emitter, Lu-177, is conjugated to XT117. Patients will receive \[177Lu\]Lu-XT117 administration at fixed dose levels at an interval of 6 weeks between each dose.

Primary outcome measures

• Treatment emergent adverse events [Time frame: Until 6 months after the last administration]
• Dose-limiting toxicities (DLTs) during the DLT evaluation period [Time frame: Up to 6 weeks after the first administration]
• Maximum tolerated dose (MTD) [Time frame: Up to 6 weeks after the first administration]
• Recommended Phase 2 Dose (RP2D) [Time frame: Through study completion, assessed up to 2 years]

Secondary outcome measures (6)

• Overall Response Rate (ORR) [Time frame: Every 6 weeks after first administration until disease progression or through study completion, assessed up to 2 years]
• Duration of Response (DOR) [Time frame: Every 6 weeks after first administration until disease progression or death or through study completion, assessed up to 2 years]
• Disease Control Rate (DCR) [Time frame: Every 6 weeks after first administration until disease progression or through study completion, assessed up to 2 years]
• Progression Free Survival (PFS) [Time frame: Every 6 weeks after first administration until disease progression or death or through study completion, assessed up to 2 years]
• Overall Survival (OS) [Time frame: 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 [Time frame: 1、4、24、48、72 and 168 hours after first administration]

Eligibility criteria

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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Medical Center, Chinese PLA General Hospital — Beijing

Publications

• Liu H, Guo R, Zhang X, Ji H, Sun S, Sun S, Liu J, Yang Z, Wang R. Safety and efficacy of 177Lu-FAPI-XT radioligand therapy in patients with advanced sarcoma and other cancer entities: first-in-human, dose-escalation study. Eur J Nucl Med Mol Imaging. 2026 Feb;53(3):1869-1880. doi: 10.1007/s00259-025-07617-0. Epub 2025 Oct 15. PMID 41087606

Identifiers

NCT: NCT06211647 · XT-XTR017-1-01 V1.1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗