A Phase II, Open-Label Study to Assess Safety and Management Change Using 68Ga-THP PSMA PET/CT in Patients with High-Risk Primary Prostate Cancer or Biochemical Recurrence After Radical Treatment: The PRONOUNCED Study

Our objectives were to assess the safety and clinical impact of a novel, kit-based formulation of 68Ga-tris(hydroxypyridinone) (68Ga-THP) prostate-specific membrane antigen (PSMA) for PET/CT in guiding the management of patients with prostate cancer. Methods: Patients were prospectively recruited to group A (high-risk untreated prostate cancer; Gleason score ≥ 4 + 3, or prostate-specific antigen (PSA) level > 20 ng/mL or clinical stage > T2c), group B (biochemical recurrence and eligible for salvage treatment after radical prostatectomy with 2 consecutive rises in PSA with a 3-mo interval between reads and a final PSA level > 0.1 ng/mL or a PSA level ≥ 0.5 ng/mL), or group C (biochemical recurrence with radical curative radiotherapy or brachytherapy at least 3 mo before enrollment, and an increase in PSA level > 2.0 ng/mL above the nadir level after radiotherapy or brachytherapy). Patients underwent evaluation with PET/CT 60 min after intravenous administration of 160 ± 30 MBq of 68Ga-THP PSMA. Safety was assessed through vital signs, cardiovascular profile, serum hematology, biochemistry, urinalysis, PSA, and adverse events (AEs). A change in management was reported when the predefined clinical management of the patient was altered as a result of the 68Ga-THP PSMA PET/CT findings. Results: Forty-nine patients were evaluated with PET/CT: 20 in group A, 21 in group B, and 8 in group C. No patients experienced serious AEs, discontinued the study because of AEs, or died during the study. Two patients had treatment-emergent AEs attributed to 68Ga-THP PSMA (pruritus in one patient and a rash at the intravenous catheter site in another). A management change secondary to the PET/CT findings occurred in 42.9% of all patients: 30% in group A, 42.9% in group B, and 75% in group C. Conclusion: 68Ga-THP PSMA was safe to use, with no serious AEs and no AEs resulting in withdrawal from the study. 68Ga-THP PSMA PET/CT changed the management of 42.9% of the study population, comparable to studies using other PSMA tracers. These data form the basis of a planned phase III study of 68Ga-THP PSMA in patients with prostate cancer.