No long-term animal studies were performed to evaluate the carcinogenicity potential of gallium Ga 68 gozetotide.

The efficacy of ILLUCCIX for PET of PSMA-positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy has been established based on a study of another formulation of gallium Ga 68 gozetotide. Below is a display of the results of the prospective, open label study PSMA-PreRP (NCT03368547 and NCT02919111).

This two-center study enrolled 325 patients with biopsy-proven prostate cancer who were considered candidates for prostatectomy and pelvic lymph node dissection. All enrolled patients met at least one of the following criteria: serum prostate-specific antigen (PSA) of at least 10 ng/mL, tumor stage cT2b or greater, or Gleason score greater than 6. Each patient received a single gallium Ga 68 gozetotide PET/CT or PET/MR from mid-thigh to skull base.

A total of 123 patients (38%) proceeded to standard-of-care prostatectomy and template pelvic lymph node dissection and had sufficient histopathology data for evaluation (evaluable patients). Three members of a pool of six central readers independently interpreted each PET scan for the presence of abnormal gallium Ga 68 gozetotide uptake in pelvic lymph nodes located in the common iliac, external iliac, internal iliac, and obturator subregions bilaterally as well as in any other pelvic location. The readers were blinded to all clinical information except for the history of prostate cancer prior to definitive treatment. Extrapelvic sites and the prostate gland itself were not analyzed in this study. For each patient, gallium Ga 68 gozetotide PET results and reference standard histopathology obtained from dissected pelvic lymph nodes were compared by region (left hemipelvis, right hemipelvis, and other).

For the 123 evaluable patients, the mean age was 65 years (range 45 to 76 years), and 89% were white. The median serum PSA was 11.8 ng/mL. The summed Gleason score was 7 for 44%, 8 for 20%, and 9 for 31% of the patients, with the remainder of the patients having Gleason scores of 6 or 10.

Table 7compares majority PET reads to pelvic lymph node histopathology results at the patient-level with region matching, such that at least one true positive region defines a true positive patient. As shown, approximately 24% of subjects studied were found to have pelvic nodal metastases based on histopathology (95% confidence interval: 17%, 32%).

Table 7: Patient-Level Performance of Gallium Ga 68 Gozetotide PET for Detection of Pelvic Lymph Node Metastasis* in the PSMA-PreRP Study (n=123)

*with region matching where at least one true positive region defines a true positive patient

**PPV: positive predictive value, NPV: negative predictive value

Among the pool of six readers, sensitivity ranged from 36% to 60%, specificity from 83% to 96%, positive predictive value from 38% to 80%, and negative predictive value from 80% to 88%.

In an exploratory subgroup analysis based on summed Gleason score, there was a numerical trend toward more true positives in patients with Gleason score of 8 or higher compared to those with Gleason score of 7 or lower.

An exploratory analysis was performed to estimate the sensitivity and specificity for pelvic nodal metastasis detection in all scanned patients, including the patients who were lacking histopathology reference standard. An imputation method was used based on patient-specific factors. This exploratory analysis resulted in an imputed sensitivity of 47%, with a 95% confidence interval ranging from 38% to 55%, and an imputed specificity of 74%, with a 95% confidence interval ranging from 68% to 80% for all patients imaged with gallium Ga 68 gozetotide PET.