This is a First-In-Human (FIH) study of [68Ga]-FF58 to characterize the imaging properties, safety, biodistribution and dosimetry properties of [68Ga]-FF58 in adults with relapsed or refractory (r/r) glioblastoma multiforme (GBM), breast cancer (BC) that has metastasized to the brain, gastroesophageal adenocarcinoma (GEA) or pancreatic ductal adenocarcinoma (PDAC) expected to overexpress alpha-v beta 3 (αvβ3) and alpha-v beta 5 (αvβ5) integrins.
Approximately 80 patients will be enrolled into the study, 20 patients with GBM, 20 patients with BC that has metastasized to the brain, 20 with GEA and 20 with PDAC.
The study will have an imaging characterization part and an expansion part. In the imaging characterization part, approximately 24 patients will be enrolled, 6 with r/r GBM, 6 with BC that has metastasized to the brain, 6 with GEA and 6 with PDAC.
Both parts of the study (imaging characterization and expansion) will include a dosimetry sub-group in which the distribution, pharmacokinetics (PK), radiation dosimetry and absorbed doses in tissue and tumor will be assessed.
All patients enrolled in the study will receive a single dose of [68Ga]-FF58 and undergo [68Ga]-FF58 PET imaging at different timepoints on Day 1 as well as conventional imaging (high resolution CT or MRI).
The estimated study duration for each individual patient is approximately 44 days (including screening period of 28 days and 14 days of follow-up (FU)).
Signed informed consent must be obtained prior to participation in the study
Patients with histologically or cytologically confirmed and documented r/r GBM that has progressed after prior radiation therapy and have not received prior bevacizumab OR patients with BC that has metastasized to the brain and who should have at least one newly diagnosed brain metastasis that has not been resected or irradiated, or has been irradiated and progressed OR patients with histologically or cytologically confirmed and documented locally advanced or metastatic GEA (i.e., adenocarcinoma of the stomach (intestinal subtype), esophagus, or gastroesophageal junction), either untreated or r/r after one or more lines of treatment OR patients with histologically or cytologically confirmed and documented locally advanced or metastatic PDAC, either untreated or r/r after one or more lines of treatment.
Creatinine clearance (calculated using Cockcroft-Gault formula) <40 mL/min.
Unmanageable bladder outflow obstruction or urinary incontinence.
QTcF > 480 msec on screening ECG or congenital long QT syndrome.
Any condition that requires chronic treatment with anticoagulants or antiplatelet agents
Patients with a known bleeding disorder
Administration of a radiopharmaceutical within a period corresponding to 10 half-lives of the radionuclide used prior to injection of [68Ga]-FF58.
Pregnant women. Women who are breastfeeding must express and discard breast milk for 12 hours after [68Ga]-FF58 administration and must also stop breast feeding during this same period. Males and females must abstain from sexual intercourse for 12 hours after [68Ga]-FF58 administration.
Total bilirubin > 1.5 x ULN (except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 x ULN) or direct bilirubin > 1.5 x ULN
Alanine aminotransferase (ALT) > 3 x ULN, except for patients that have tumor involvement of the liver, who are excluded if ALT > 5 x ULN
Aspartate aminotransferase (AST) > 3 x ULN, except for patients that have tumor involvement of the liver, who are excluded if AST > 5 x ULN
Novartis Investigative Site