CTT1057, a Small Molecular Inhibitor of PSMA, as a Novel Imaging Agent of Neovascularization in Renal Cell Carcinoma

CTT has developed a PET imaging agent, CTT1057, labeled with 18F, that is based on a small
molecule core and targets an extracellular region of PSMA with high affinity. Although
comparable to other inhibitors in terms of affinity for PSMA, this unique class of
phosphoramidate agents are the only known irreversible PSMA inhibitors. Due to its
irreversible binding to PSMA and rapid uptake by PSMA-expressing cancer cells, accumulation
at the cancer target is expected to be rapid, specific and sensitive. PSMA expression has
been reported in renal cell carcinoma cells, making it possible that CTT1057 may have utility
in detecting these tumors.

Ten patients will be enrolled in parallel in two cohorts:

- (Cohort A) Patients with presumed metastases on conventional imaging, with at least one
presumed metastatic lesion measuring > 1.5 cm in diameter (long-axis for non-node target
lesions; short axis for lymph node), with planned biopsy of a metastatic lesion (N = 5).

- (Cohort B) Patients with primary renal mass measuring > 7 cm on conventional imaging,
with presumptive or histologically confirmed diagnosis of renal cell carcinoma, with
planned nephrectomy. Patients may or may not have nodal or distant metastases on
conventional imaging (N = 5) Participants receive a single IV dose (370 MBq, or 10 mCi)
of CTT1057 in this trial. Combined PET/MR or PET/CT imaging (kidney + whole body) will
be performed following tracer injection. Patients in cohort A (metastatic renal cell
carcinoma) will undergo planned metastatic lesion biopsy within 12 weeks following
CTT1057 PET imaging. Patients in cohort B (primary renal cell carcinoma) will have
planned nephrectomy within 12 weeks following CTT1057 PET imaging.

The one-time nominal injected dose will be 370 MBq (10 mCi). Estimated mass dose is 20 µg of
CTT1057. Dose will be in a volume of 3 - 5 mL, and will be injected intravenously as a bolus
injection.

Vital signs, adverse event assessment, and 12 lead ECGs will be performed on day 1 before and
after dosing.

Inclusion Criteria:

- Patients age ≥18 years old

- Histologically confirmed renal cell carcinoma

- Adequate organ function including:

- - Platelet count of > 50,000/mm3

- - Neutrophil count of > 1000/mm3

- - Serum Cr < 1.5 x ULN or estimated GFR > 60 ml/min based upon Cockroft-Gault equation

- - Proteinuria < 1 g/24 hours based upon 24 hour urine collection or spot urine
protein/creatinine ratio

- - AST and ALT < 2.5 x ULN (< 5 x ULN in patients with known liver metastases)

- - Total bilirubin < 1.5 x ULN (< 3 x ULN in patients with known/suspected Gilbert's
disease)

- ECOG performance status of 0 or 1

- Able to provide written informed consent and willing to comply with protocol
requirements

- No contra-indication to MR including severe claustrophobia, incompatible aneurysm
clips or cardiac pacemaker

- For participants of childbearing potential, not pregnant, and use of effective
contraceptive methods during the trial and within 6 months following radiotracer
injection

- Cohort A only: Presence of at least three distinct metastatic lesions by standard
imaging including whole body bone scan + cross-sectional imaging of the abdomen and
pelvis obtained within 12 weeks prior to protocol scan

- Cohort B only: (N = 5 evaluable patients): Planned nephrectomy within 12 weeks
following protocol scan

Exclusion Criteria:

- Patients with or with a history of uncontrolled bleeding diathesis

- Inadequate venous access per assessment of treating health care provider

- Receipt of radioisotope within 5 physical half-lives prior to trial enrollment

- Prior treatment with alpha radiation therapy (Radium Ra 223 chloride; Xofigo™) during
the previous 60 days

- Have a medical condition or other circumstances that, in the opinion of the
investigator would significantly decrease the chances of obtaining reliable data,
achieving the study objectives, or completing the trial.

- Prior history of any other malignancy within past three years, except melanomatous
skin cancer or carcinoma in situ.