Study of [68Ga]-FF58 in Patients With Selected Solid Tumors Expected to Overexpress αvβ3 and αvβ5 Integrins.

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 were planned to be enrolled into the study, 20 patients with GBM, 20 patients with BC that had metastasized to the brain, 20 with GEA and 20 with PDAC.

The study included an imaging characterization part and an expansion part. In the imaging characterization part, approximately 24 patients were planned to be enrolled, 6 with r/r GBM, 6 with BC that had metastasized to the brain, 6 with GEA and 6 with PDAC. Due to the early termination of the study, the expansion part was not started.

Both parts of the study (imaging characterization and expansion) included a dosimetry sub-group in which the distribution, pharmacokinetics (PK), radiation dosimetry and absorbed doses in tissue and tumor were to be assessed. However, no patients were enrolled in the dosimetry sub-group.

All patients enrolled in the study received a single dose of \[68Ga\]-FF58 and underwent \[68Ga\]-FF58 positron emission tomography (PET) imaging at different timepoints on Day 1 as well as conventional imaging (high resolution computed tomography (CT) or magnetic resonance imaging (MRI)).

The estimated study duration for each individual patient was approximately 44 days (including screening period of 28 days and 14 days of follow-up (FU)).

Eligibility Criteria:
Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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