On September 12, 2018 Progenics Pharmaceuticals, Inc. (NASDAQ:PGNX), an oncology company developing innovative medicines and imaging analysis technology for targeting and treating cancer, reported top line data from its Phase 3 study of 1404, the Company’s prostate specific membrane antigen (PSMA)-targeted small molecule SPECT/CT imaging agent that is designed to visualize prostate cancer (Press release, Progenics Pharmaceuticals, SEP 12, 2018, View Source [SID1234529673]).
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The Phase 3 trial evaluated the specificity of 1404 imaging to identify patients without clinically significant prostate cancer and sensitivity to identify patients with clinically significant disease. The study dosed 471 patients in the U.S. and Canada with low-grade prostate cancer, whose biopsy indicated a histopathologic Gleason grade of ≤ 3+4 severity and/or were candidates for active surveillance. Median PSA levels for patients dosed in trial was 5.58 ng/mL (range 0.69 – 16.03). In the study, 1404 detected clinically meaningful prostate cancer with specificity ranging among the three readers from 71-75% (95% confidence interval CI of 64% to 80%). The co-primary endpoint of sensitivity was not met and ranged amongst the three readers from 47-51% (95% CI of 41% to 56%). The trial protocol required the lower limit of the two-sided 95% CI for both specificity and sensitivity to exceed 60%.
The most frequent treatment related events included headache (2.3%), dizziness (1.1%) and fatigue (0.8%).
"These top line Phase 3 results of 1404 are inconsistent with the prior Phase 2 data which showed significantly higher sensitivity rates," stated Mark Baker, CEO of Progenics. "We are currently conducting a thorough analysis of the full data set to understand the factors that may have contributed to this outcome and determine the appropriate development path for this novel agent in patients with low-grade prostate cancer. We plan to complete this review in the next quarter."
Mr. Baker added, "We believe that PSMA-targeted imaging holds tremendous promise to improve the detection, staging and monitoring of prostate cancer. These results do not impact our view of the PyL PET imaging agent in patients with recurrent or metastatic prostate cancer as we head into our Phase 2/3 data readout next quarter, and we remain on track to initiate our second Phase 3 study by year-end. Our oncology therapeutic programs continue to move forward, including the ongoing commercial launch of AZEDRA for the treatment of pheochromocytoma or paraganglioma. In addition, we anticipate finalizing our clinical development plan with the U.S. FDA for 1095 in metastatic castration-resistant prostate cancer (mCRPC) in the fourth quarter and expect our partner Bayer to initiate a Phase 1 study of PSMA-TTC in patients with mCRPC by year end 2018."
Progenics Reports Phase 3 Results for 1404 Page 2
About the Phase 3 1404 Trial
The Phase 3 trial was a multi-center, multi-reader, open-label trial, comparing 1404 SPECT/CT imaging in men who had a diagnostic trans-rectal ultrasound (TRUS) guided biopsy with a histopathologic finding of Gleason score ≤3+4 who were candidates for active surveillance and were undergoing routine biopsy or voluntary radical prostatectomy (RP) with or without a pelvic lymph node dissection. This study was designed to evaluate the sensitivity and specificity of 1404 SPECT/CT image assessments to correctly identify subjects with previously unknown clinically significant prostate cancer in two cohorts: low grade prostate cancer who had elected to undergo RP; and very low risk (VLR) prostate cancer per 2016 National Comprehensive Cancer Network Guidelines who were scheduled to undergo routine prostate biopsy. Subjects received a single dose of 1404 followed by whole body planar and SPECT/CT (pelvic) imaging. In accordance with standard of care procedures, subjects underwent either voluntary RP or prostate biopsy within 42 days after study drug dosing. 1404 image data was collected by a central imaging core laboratory and evaluated for visible uptake within the prostate gland and then compared against central histopathology as the truth standard.
About 1404, an Imaging Compound Targeting Prostate Specific Membrane Antigen
Progenics’ molecular imaging radiopharmaceutical product candidate 1404 targets the extracellular domain of prostate specific membrane antigen (PSMA), a protein amplified on the surface of > 95% of prostate cancer cells and a validated target for the detection of primary and metastatic prostate cancer. 1404 is labeled with Technetium-99m, a gamma-emitting isotope that is widely available, is easy to prepare, and is attractive for nuclear medicine imaging applications. The image created provides the opportunity to visualize cancer, potentially allowing for improved detection and staging, more precise biopsies, and a targeted treatment plan including active surveillance as a disease management tool.
About Prostate Cancer
Prostate cancer is the second most common form of cancer affecting men in the United States: an estimated one in seven men will be diagnosed with prostate cancer in his lifetime. The American Cancer Society estimates that each year approximately 161,360 new cases of prostate cancer will be diagnosed and about 26,730 men will die of the disease. Approximately 2.9 million men in the U.S. currently count themselves among prostate cancer survivors.