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).
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
26
64Cu-LNTH-1363S, is a highly selective, high affinity FAP inhibitor (FAPi) that is radiolabeled with Copper-64 (64Cu) for PET/CT Imaging,
City of Hope
Duarte, California, United States
RECRUITINGUC Irvine Health - Chao Family Comprehensive Cancer Center
Orange, California, United States
RECRUITINGStanford Hospital & Clinics
Stanford, California, United States
RECRUITINGBAMF Health, Inc.
Grand Rapids, Michigan, United States
RECRUITINGCincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
RECRUITINGPrimary 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.
Time frame: During serial PET/CT scans taken on Day 1 at the following timepoints at 0.5 hour ± 10 minutes, 1 hour ±10 minutes, 2 hours ± 15 minutes, 4 to 6 hours, and 24 hours ± 4 hours post study intervention administration.
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).
Time frame: During serial PET/CT scans taken on Day 1 at the following timepoints at 0.5 hour ± 10 minutes, 1 hour ±10 minutes, 2 hours ± 15 minutes, 4 to 6 hours, and 24 hours ± 4 hours post study intervention administration.
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.
Time frame: Post surgery tissue collection to end of study
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).
Time frame: Part1: From IP administration until the Day 7 (± 1 day) telephone follow up. Part 2: From time of IP administration to until post-surgery IHC sample collection.
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.
Time frame: From Day 1 until the end of the Scheduled Surgery: IHC sample collection
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.
Time frame: Continuous ECG monitoring at Visit 2
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.
Time frame: From start of Part 2 to 6 patients enrolled with qualifying imaging
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