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

Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06211647
• Other study ID #: XT-XTR017-1-01 V1.1
• Status: Recruiting
• Phase: Phase 1
• Start date: January 2024
• Est. completion date: December 2026

Study information

• Verified date: January 2024
• Source: Chinese PLA General Hospital
• Contact: Ang Yin
• Phone: (+86)010-52805808
• Email: ang.yin[@]sinotau.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

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.

Locations

Country	Name	City	State
China	The First Medical Center, Chinese PLA General Hospital	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Ruimin Wang	Sinotau Pharmaceutical Group

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment emergent adverse events	Incidence and severity of treatment emergent adverse events will be assessed as per CTCAE v5.0).	Until 6 months after the last administration
Primary	Dose-limiting toxicities (DLTs) during the DLT evaluation period	A DLT is defined as any drug-related toxicity that fulfills certain criteria predescribed in the study protocol.	Up to 6 weeks after the first administration
Primary	Maximum tolerated dose (MTD)	MTD will be determined by 3+3 dose escalation design.	Up to 6 weeks after the first administration
Primary	Recommended Phase 2 Dose (RP2D)	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.	Through study completion, assessed up to 2 years
Secondary	Overall Response Rate (ORR)	ORR is defined as the proportion of participants with best overall response of Complete Response (CR) or Partial Response (PR) as measured by RECIST v1.1.	Every 6 weeks after first administration until disease progression or through study completion, assessed up to 2 years
Secondary	Duration of Response (DOR)	DOR is the time from the date of the first documented response (CR or PR) to the date of the first radiologically documented disease progression or death due to disease according to RECIST v1.1.	Every 6 weeks after first administration until disease progression or death or through study completion, assessed up to 2 years
Secondary	Disease Control Rate (DCR)	DCR is the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) according to RECIST v1.1	Every 6 weeks after first administration until disease progression or through study completion, assessed up to 2 years
Secondary	Progression Free Survival (PFS)	PFS is defined as the interval from the date of first dosing to the date of first demonstrated disease progression, or to the last date of known progression-free condition of the patient, or to the date of death (based on RECIST 1.1).	Every 6 weeks after first administration until disease progression or death or through study completion, assessed up to 2 years
Secondary	Overall Survival (OS)	OS is defined as the interval from the date of first dosing to the date of death for any cause, or to the last date of known survival.	Every 6 weeks after first administration until death, assessed up to 2 years
Secondary	Radiation dosimetry of [177Lu]Lu-XT117 to whole body, lesions, organs, and selected regions of interest	Radiation dosimetry is assessed by SPECT/CT and/or planar images.	1?4?24?48?72 and 168 hours after first administration