Presentation Authors: William J. Ellis*, Seattle, WA, Bryan J. Donnelly, Calgary, AB, Michael A. Gorin, Baltimore, MD, Frédéric Pouliot, Quebec, Canada, Hao G. Nguyen, Peter R. Carroll, San Francisco, CA, Douglas Scherr, New York, NY, Stephan Probst, Montreal, QC, Lawrence Saperstein, New Haven, CT, Neil Fleshner, Toronto, ON, Paul Maroni, Aurora, CO, Khushboo Shah, Nancy Stambler, Vincent A. DiPippo, Thomas Strack, Syed Mahmood, Jessica Jensen, Vivien Wong, New York, NY, Mohamad Allaf, Baltimore, MD
Introduction: 99mTc-MIP-1404 (1404) is a small molecule SPECT imaging agent that binds to prostate-specific membrane antigen (PSMA) allowing for the detection of prostate cancer (PCa). SPECT/CT is an imaging technique with advantages over PET/CT that include a ubiquitous, low cost option for PCa imaging. The objective of this trial was to evaluate the sensitivity and specificity of 1404 SPECT/CT to detect clinically significant PCa in men with low-grade PCa at initial biopsy who were candidates for active surveillance.
Methods: This Phase 3 trial was a multi-center, multi-reader, open-label trial evaluating 1404 SPECT/CT imaging in men who had biopsy proven PCa with Gleason score (GS) â‰¤3+4 within 12 months of enrollment and were candidates for active surveillance, planning to undergo follow-up biopsy or radical prostatectomy with or without a pelvic lymph node dissection. A single dose of 1404 (20 Â± 3 mCi) was administered by intravenous injection followed by whole body planar and SPECT/CT (pelvic) imaging 3-6 hours later. 1404 images were reviewed by three independent, central imaging readers and evaluated for uptake consistent with clinically significant PCa. These findings were then compared against central histopathology as the truth standard. Clinically significant disease was defined as GS >3+4 or 3+4 with â‰¥10% pattern 4, and either any GS with â‰¥pT3 disease (radical prostatectomy) or GS 3+3 with intraductal carcinoma of prostate (biopsy). The co-primary endpoints of specificity and sensitivity were calculated for correctly identifying subjects with clinically significant prostate cancer, requiring a lower limit of the two-sided 95% confidence intervals (CIs) to exceed 60%.
Results: 1404 SPECT/CT was evaluated for its diagnostic performance in 465 men. The median PSA level for patients dosed in the trial was 5.58 ng/mL (range: 0.69-16.03). 1404 was very well tolerated. The most frequent adverse events included headache (2.3%), dizziness (1.1%), and fatigue (0.8%). 1404 SPECT/CT detected clinically significant PCa among the three readers with sensitivity of 47-51% (95% CI: 41-56%), specificity of 71-75% (95% CI: 64-80%), and PPV of 75-77% (95% CI: 68-83%).
Conclusions: 1404 SPECT/CT achieved the co-primary endpoint of specificity, successfully identifying patients without clinically significant PCa. However, the sensitivity endpoint did not achieve the pre-specified lower-bound. ClinicalTrials.gov: NCT02615067
Source of Funding: Progenics Pharmaceuticals, Inc.