Clinical trial NCT06211647: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
Collaborators: name: Sinotau Pharmaceutical Group
First posted: 2024-01-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Treatment emergent adverse events
timeFrame: Until 6 months after the last administration
measure: Dose-limiting toxicities (DLTs) during the DLT evaluation period
timeFrame: Up to 6 weeks after the first administration
measure: Maximum tolerated dose (MTD)
timeFrame: Up to 6 weeks after the first administration
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Through study completion, assessed up to 2 years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Every 6 weeks after first administration until disease progression or through study completion, assessed up to 2 years
measure: Duration of Response (DOR)
timeFrame: Every 6 weeks after first administration until disease progression or death or through study completion, assessed up to 2 years
measure: Disease Control Rate (DCR)
timeFrame: Every 6 weeks after first administration until disease progression or through study completion, assessed up to 2 years
measure: Progression Free Survival (PFS)
timeFrame: Every 6 weeks after first administration until disease progression or death or through study completion, assessed up to 2 years
measure: Overall Survival (OS)
timeFrame: Every 6 weeks after first administration until death, assessed up to 2 years
measure: Radiation dosimetry of [177Lu]Lu-XT117 to whole body, lesions, organs, and selected regions of interest
timeFrame: 1、4、24、48、72 and 168 hours after first administration
Other outcomes:
Locations:
city: Beijing
country: China
facility: The First Medical Center, Chinese PLA General Hospital
Study officials:
affiliation: The First Medical Center, Chinese PLA General Hospital
name: Ruimin Wang
role: PRINCIPAL_INVESTIGATOR
References: