Piflufolastat F 18 PET/CT in Patients With Suspected, or at High Risk for Metastatic ccRCC

Phase 2/3 Open-Label Multicenter Study to Assess the Diagnostic Performance of Piflufolastat F 18 PET/CT on Intended Clinical Management in Patients With Suspected, or at High Risk for Metastatic ccRCC

This study is being conducted to test whether an imaging technique called a "piflufolastat F 18 PET/CT" imaging scan can be used to diagnose and describe the extent of clear cell Renal Carcinoma in patients.

The main questions it aims to answer are:

• What is the most appropriate dose and scan timing window for piflufolastat F 18 PET/CT for patients with clear cell Renal Cell Carcinoma (ccRCC) with known metastatic disease?
• Ability of piflufolastat F 18 PET/CT to detect metastatic of lesions ccRCC in patients with suspected metastatic disease and those at high risk for metastatic disease (the cancer has spread beyond the kidney) and impact of the imaging on clinical management of the kidney cancer?

Participants will:

• Receive a single injection of piflufolastat F 18 injection followed by imaging scans.
• Be contacted via telephone to ask about any reactions or discomforts they may have after the piflufolastat F 18 injection.
• May be followed for up to 6 months to collect data about disease progression.

This is an adaptive Phase 2/3, open-label, multi-center, single-arm study designed to evaluate diagnostic performance of piflufolastat F 18 PET/CT in the staging of patients suspected of having, or who are at high risk for, metastatic ccRCC and its impact on intended clinical management.

Inclusion Criteria:

1. Male and female patients ≥18 years of age
2. Patients must have the ability to understand and sign an approved informed consent form (ICF)
3. Patients must have the ability to understand and comply with all protocol requirements.
4. Subjects should satisfy the following criteria:

1) For the Phase 2 (dose optimization) portion of the study: ccRCC patients with at least one suspected metastatic lesion identified by conventional imaging scans at the time of enrolling in the study 2) For the Phase 3 portion of the study: Patients must be suspected of having or be at high risk for developing metastatic disease. This patient population is generally defined as one of the following:

1. Newly diagnosed ccRCC patients or post- nephrectomy/post-partial nephrectomy patients with radiographically suspected ccRCC metastatic disease by conventional imaging (CI) planned for biopsy to confirm metastatic disease

2. T2B-T4, N0, M0 as assessed by conventional imaging (CI) at initial staging pre-nephrectomy/pre-partial nephrectomy

3. Confirmed ccRCC with high risk of metastatic recurrence post nephrectomy pT1b or higher with G3-4 N0( or pNX where clinically N0)M0. Patients must be N0, M0 on the follow up CI not more than 60 days prior to piflufolastat F18 scan

4. Patients with new radiographically suspected oligometastatic ccRCC (up to 5 metastatic lesions at presentation) planned for nephrectomy or biopsy for lesion verification of at least one suspected metastatic lesion

   5. Completed staging evaluation with baseline conventional imaging (contrast-enhanced CT or contrast-enhanced MRI of the chest, abdomen, and pelvis, or skull base to mid thigh FDG PET)less than or equal to 60 days prior to piflufolastat F 18 PET/CT (Day 1). If baseline conventional imaging was performed outside of the 60-day window, it can be repeated during the screening period provided that there are at least 24 hours between conventional imaging and piflufolastat F 18 (Day 1). Conventional imaging must be available for central evaluation.

   6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

   7. Patients with life expectancy of at least 6 months as determined by the investigator or treating physician.

   Exclusion Criteria:

   1. Patients administered any high energy (>300 KeV) gamma-emitting radioisotope within five (5) physical half-lives, prior to Day 1.
   2. Known hypersensitivity to the components of piflufolastat F 18 or its analogs.
   3. Pregnant or breastfeeding females. Pregnancy testing will be performed in potentially childbearing women prior to piflufolastat F 18 administration on Day 1.
   4. Prior imaging with girentuximab or any PSMA-PET agent or any non-approved ccRCC imaging agent within the last 3-months prior to piflufolastat F 18 PET/CT.
   5. Patients who are in active systemic therapy for metastatic ccRCC prior to piflufolastat F 18 PET/CT. 30-day (12 weeks for immunotherapy) washout period is required from the last dose of systemic therapy to piflufolastat F18 administration.
   6. Patients who are expected to receive anti-cancer treatment between baseline conventional imaging, piflufolastat F 18 PET/CT, biopsy, or surgery.
   7. Evidence of any other active malignancy within the past 3 years, except non-melanoma skin cancer, carcinoma in situ, adequately treated Stage 1 cancer from which the patent is in remission and has been in remission for a minimum of 2 years. Any adjuvant or maintenance systemic chemotherapy must have been completed at least 30 days prior to piflufolastat F 18 PET/CT administration (12-week washout if immunotherapy).
   8. Patients with any medical condition or other circumstances that, in the opinion of the investigator, compromise the safety or compliance of the subject to produce reliable data or completing the study.
   9. Patients requiring dialysis.