64Cu-LNTH-1363S in Patients With Sarcoma or Gastrointestinal Tract Cancer

Part 1 will determine the biodistribution, dosimetry, optimal dose (radioactivity) and imaging time window of 64Cu-LNTH-1363S in 6 evaluable patients with supposed FAP-expressing solid tumors (metastatic sarcomas). All six patients will receive 8 ± 1 mCi (~90 μg mass dose) in this study. All images will undergo analysis by blinded central readers. Optimal radioactivity and timing window will be determined based on image quality scores and measured tumor-to-background ratio. Part 1 of the study will last approximately 3 weeks for each patient and includes a Screening Period (up to 14 days), a 1-day Intervention Period and a Safety Follow-up Period (7 days post dose).

Part 2 will evaluate 64Cu-LNTH-1363S correlation with FAP expression measured by IHC (SUVmax and SUVmean vs IHC score) in 20 evaluable patients with non-metastatic, operable, supposed FAP-expressing solid tumors (sarcomas, esophageal, gastric, pancreatic, colorectal) planned for surgery within 60 days (from study imaging). If the optimal radioactivity determined from Part 1 is less than 8 ± 1 mCi, the first 6 patients in Part 2 will be used to validate this optimal radioactivity.

Part 2 of the study will last approximately 10 to 11 weeks and includes: a Screening Period (up to 14 days), a 1-day Intervention Period, a 1 day Safety Followup Period (Day 2) and a Scheduled Surgery IHC Sample Collection Period (from Day 2 to Day 60).

Both Part 1 and Part 2 of the study will also monitor cardiac safety by detecting changes in HR, T wave, ST segment and other ECG parameters and characterizing the concentration-response relationship of 64Cu-LNTH-1363S for QT and corrected QT interval (QTc) prolongation.

Inclusion criteria

Part 1

Patients are eligible to be included in the study only if all of the following criteria apply:

• 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.
• Adequate renal function as determined by a calculated creatinine clearance ≥ 60 mL/min (Cockcroft Gault equation).
• Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin (β-hCG) test and must not be breastfeeding. WOCBP must agree to use a highly effective method of contraception during the study and for 28 days after the last injection of the study drug.
• Male subjects who are able to father a child must agree to avoid impregnating a partner, to adhere to a highly effective method of contraception and to not donate sperm during the study and for 28 days after the last injection of the study drug.

Inclusion criteria

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 must have histological, pathological, and/or cytological confirmation of a sarcoma or GIT cancers e.g., esophageal, gastric, pancreatic, colorectal cancer.
• Patients must have suspected FAP expressing sarcoma or GIT cancers and planned for surgery within 60 days (from study imaging).
• Patients must be willing to consent to provide sufficient and adequate tumor tissue samples (formalin fixed, paraffin embedded sample), from their planned surgery after participating in study imaging.
• Adequate renal function as determined by a calculated creatinine clearance ≥ 60 mL/min (Cockcroft Gault equation).
• Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin (β-hCG) test and must not be breastfeeding. WOCBP must agree to use a highly effective method of contraception during the study and for 28 days after the last injection of the study drug.
• Male subjects who are able to father a child must agree to avoid impregnating a partner, to adhere to a highly effective method of contraception and to not donate sperm during the study and for 28 days after the last injection of the study drug.

Exclusion criteria

Part 1

Patients are excluded from the study if any of the following criteria apply:

• 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.
• Patients who have had systemic anti-cancer therapy administered in the 14 days prior to IP administration.
• Has undergone or plans to undergo PET or single-photon emission computerized tomography (SPECT) imaging with any other FAPi imaging agent within 6 months prior to or after participating in this trial.
• History of QT/QTc interval prolongation, a marked baseline QT/QTc interval prolongation (e.g., repeated demonstration of a QTc interval, calculated with Fridericia's correction, > 450 milliseconds) or taking medication known to cause QT/QTc prolongation.
• A history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome).

Exclusion criteria

Part 2

• Patients who have had neoadjuvant anti-cancer therapy administered in the 14 days prior to IP administration.
• Evidence of metastatic or advanced, inoperable disease.
• Unlikely to comply with protocol procedures, restrictions and requirements and judged by the investigator to be unsuitable for participation.
• 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.
• Has undergone or plans to undergo PET or SPECT imaging with any other FAPi imaging agent within 6 months prior to or after participating in this trial.
• History of QT/QTc interval prolongation, a marked baseline QT/QTc interval prolongation (e.g., repeated demonstration of a QTc interval, calculated with Fridericia's correction, > 450 milliseconds) or taking drugs known to cause QT/QTc prolongation.
• A history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome