This is a multicenter, open-label, prospective Phase 1/2a study to assess safety and tolerability, establish dosimetry and to identify an optimal imaging dose (radioactivity) and imaging time window of 64Cu-LNTH-1363S, and to compare its imaging biodistribution with FAP expression by IHC in patients with sarcomas or GIT cancers. The study will be conducted in 2 parts (Part 1 and Part 2).
Patient must be ≥ 15 years of age and must have provided written informed consent and assent, where applicable (by patient or legal guardian). Those aged ≥15 to <18 years must weigh at least 55 kg.
Patients with suspected FAP-expressing metastatic sarcoma.
Patients must have histological, pathological, and/or cytological confirmation of a metastatic sarcoma (e.g., undifferentiated pleomorphic sarcoma, liposarcoma, Leiomyosarcoma, myxofibrosarcoma, solitary fibrous tumor, Ewing's sarcoma, synovial sarcoma, sarcoma not otherwise specified, osteosarcoma).
Patients must be willing to consent to provide sufficient and adequate archived tumor tissue samples (formalin fixed, paraffin embedded sample), preferably from a biopsy of a tumor lesion obtained either at the time of or after the diagnosis of disease; if archival tissue sample is unavailable, a new biopsy should be performed on the most accessible lesion(s) to obtain the tumor tissue sample.
Unlikely to comply with protocol procedures, restrictions and requirements as judged by the Investigator.
Known pregnancy or breastfeeding.
Any PET scan done within 10 physical half-lives of the PET agent prior to receiving study intervention.
Patients participating in another clinical trial at the time of screening for this study.
Sequential
64Cu-LNTH-1363S
Combination product64Cu-LNTH-1363S, is a highly selective, high affinity FAP inhibitor (FAPi) that is radiolabeled with Copper-64 (64Cu) for PET/CT Imaging,
Primary Part 1 Biodistribution of 64Cu-LNTH-1363S
Time Activity Curves (TACs) describing percentage of the injected activity versus time will be derived for selected organs and tumor lesions and absorbed radiation doses of 64Cu-LNTH-1363S in critical organs (e.g., kidneys, liver) will be estimated.
Primary Part 1 - Optimal dose (radioactivity) and imaging time window of 64Cu-LNTH-1363S
Optimal dose (radioactivity) and imaging time window will be determined by using image quality scores from blinded central reviews. Each patient will receive 8 ± 1 mCi of 64Cu-LNTH-1363S. The raw data of each patient PET scan will be re-processed using a computer program to simulate scans of the same patient with lower injected activities (6 mCi and 4 mCi).
Primary Part 2 - Correlation of 64Cu-LNTH-1363S biodistribution with Immunohistochemistry FAP expression
Correlation of 64Cu-LNTH-1363S biodistribution with FAP expression by IHC (SUVmean and SUVmax vs IHC score) and compare to circulating FAP in blood as analyzed by ELISA method.
Secondary Parts 1 and 2 Safety and Tolerability
Safety and tolerability profile of 64Cu-LNTH-1363S in patients with sarcoma and GITs based on: * Frequency and severity of adverse events (AEs) and serious AEs (SAEs) measured by Common Terminology Criteria for AEs (CTCAE) v5.0 or higher. * Changes in vital signs * Changes in laboratory parameters * Changes in electrocardiogram (ECG)parameters • Exposure-response relationships: * Relationship of AEs to exposure (dose and concentrations).
Secondary Part 1 FAP expression profile of 64Cu-LNTH-1363S in patients with sarcoma
Correlation of 64Cu-LNTH-1363S biodistribution with FAP expression by immunohistochemistry (IHC) (SUVmean and SUVmax vs IHC score) and compare to circulating FAP in blood as analyzed by ELISA method.
Secondary Part 1 and Part 2 Cardiac Safety
Monitor cardiac safety and look for signals suggesting a concentration-response relationship of 64Cu-LNTH-1363S for QT/corrected QT interval (QTc) prolongation.
Secondary Part 2 Validate optimal radioactivity in patients with sarcoma or GIT cancer
Validate optimal radioactivity in patients with sarcoma or GIT cancer, if the optimal radioactivity determined in Part 1 is less than 8 ± 1 mCi. Validation to be completed on image quality score of first 6 patients, if optimal radioactivity determined in Part 1 is less than 8 ± 1 mCi.
Exploratory Part 1 and Part 2
Develop an AI system for detecting and characterizing cancer lesion(s) expressing FAP using 64Cu-LNTH-1363S, through Correlation between automated measurement of physiological uptake of 64Cu-LNTH-1363S with manual measurement results; and through the determination of the detection rate of possible site of cancer lesion(s) with 64Cu-LNTH-1363S using an AI enabled reading system when compared to central reader assessments. Part 2: Estimation of total tumor burden using an AI enabled reading system.
Correlation between LRRC15 IHC and FAP expression
Correlation of LRRC15 expression to 64Cu-LNTH-1363S biodistribution and FAP expression (determined by IHC)
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