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

Lantheus Medical Imaging

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Sarcoma; Gastric Cancer; Esophageal Cancer; Metastatic Sarcoma; Colorectal Cancer; Pancreatic Cancer

Treatments: Combination Product: 64Cu-LNTH-1363S

Study type: Interventional

Funder types: Industry

Identifiers

NCT06298916

FAPi-1301

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 26 estimated patients

Sex: All

Ages: 15+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: Part 1

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

1. 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.
2. Patients with suspected FAP-expressing metastatic sarcoma.
3. 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).
4. 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.
5. Adequate renal function as determined by a calculated creatinine clearance ≥ 60 mL/min (Cockcroft Gault equation).
6. 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.
7. 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

1. 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.
2. Patients must have histological, pathological, and/or cytological confirmation of a sarcoma or GIT cancers e.g., esophageal, gastric, pancreatic, colorectal cancer.
3. Patients must have suspected FAP expressing sarcoma or GIT cancers and planned for surgery within 60 days (from study imaging).
4. 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.
5. Adequate renal function as determined by a calculated creatinine clearance ≥ 60 mL/min (Cockcroft Gault equation).
6. 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.
7. 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:

1. Unlikely to comply with protocol procedures, restrictions and requirements as judged by the Investigator.
2. Known pregnancy or breastfeeding.
3. Any PET scan done within 10 physical half-lives of the PET agent prior to receiving study intervention.
4. Patients participating in another clinical trial at the time of screening for this study.
5. Patients who have had systemic anti-cancer therapy administered in the 14 days prior to IP administration.
6. 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.
7. 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.
8. 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

1. Patients who have had neoadjuvant anti-cancer therapy administered in the 14 days prior to IP administration.
2. Evidence of metastatic or advanced, inoperable disease.
3. Unlikely to comply with protocol procedures, restrictions and requirements and judged by the investigator to be unsuitable for participation.
4. Known pregnancy or breastfeeding.
5. Any PET scan done within 10 physical half-lives of the PET agent prior to receiving study intervention.
6. Patients participating in another clinical trial at the time of screening for this study.
7. 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.
8. 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.
9. A history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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26 participants in 2 patient groups

Experimental Part 1

Experimental group

Description:

6 patients will receive 8 ± 1 mCi (\~90 μg mass dose) of the 64Cu-LNTH-1363S on Day 1 in the Intervention Period (raw data of each patient PET scan will be re-processed using a computer program to simulate scans of the same patient with 6 mCi and 4 mCi 64Cu injected activities).

Treatment:

Combination Product: 64Cu-LNTH-1363S

Experimental Part 2

Experimental group

Description:

First 6 evaluable patients will receive the optimal radioactivity determined in Part 1. The remaining 14 evaluable patients will receive either the optimal radioactivity determined in Part 1 (if the sum of the average image quality scores of the first 6 patients is higher or equal to 10.5), or 8 ± 1 mCi (if the sum of the average image quality scores of the first 6 patients is less than 10.5).

Treatment:

Combination Product: 64Cu-LNTH-1363S