Results of Phase 2/3 Trial of PSMA PET Imaging Agent PyL for the Detection of Prostate Cancer
Dr. Michael Morris, Associate Professor at Memorial Sloan Kettering, and a lead investigator of the trial said “these are highly encouraging results in a large, well-controlled and rigorous trial showing PyL has excellent positive and negative predictive value in assessing the distribution of disease in men with high-risk prostate cancer. Furthermore, in men intended to go to surgery, the specificity of PyL was exceedingly good. Taken together, a PyL PET avid lesion is a reliable reflection of histologically proven disease and may provide additional important information to men with prostate cancer and their doctors. That information may provide important guidance in the decision-making for their treatment.”
Phase 2/3 Trial Results
The trial examined the diagnostic performance of PSMA-targeted PET imaging agent, PyL, to detect prostate cancer in pelvic lymph nodes in patients with high risk locally advanced prostate cancer (Cohort A) and distant metastases in patients with metastatic or recurrent (Cohort B) prostate cancer. The diagnostic performance of PyL PET imaging in this “gold standard” trial was evaluated against histopathology as the standard of truth. The OSPREY study dosed 385 patients with either high-risk locally advanced prostate cancer (268) or metastatic or recurrent prostate cancer (117). The study’s co-primary endpoints were the assessment of specificity and sensitivity of PyL PET imaging in Cohort A to detect prostate cancer in pelvic lymph nodes in patients scheduled to undergo radical prostatectomy with extended pelvic lymph node dissection. Key secondary endpoints for Cohort A were positive predictive value and negative predictive value. The study also evaluated several key secondary endpoints in Cohort B, including the sensitivity and positive predictive value of PyL PET imaging in detecting metastatic prostate cancer in patients where lesion biopsies (bone, soft tissues, lymph nodes other than pelvic lymph nodes) were feasible.
In the trial, the diagnostic performance of PyL in detecting disease in pelvic lymph nodes (Cohort A) showed a high specificity (96-99% among the three blinded independent readers), meeting the first co-primary endpoint of the trial, with the lower bound of the 95th percent confidence interval (94-96%) exceeding 80%. The sensitivity of 31-42%, did not meet the second co-primary endpoint, as the lower bound of the 95th percentile confidence interval (19-30%) did not exceed the required 40%. The positive predictive value and negative predictive value of pelvic lymph node detection were 78-91% and 81-84%, respectively.
In the metastatic or recurrent prostate cancer setting (Cohort B), PyL exhibited sensitivity of 93-99% and PPV of 81-88% in detecting metastatic lesions. Specificity and negative predictive value were not endpoints specified in the protocol for Cohort B as all men in Cohort B were suspected to have disease.
18F‐DCFPyL was very well tolerated. A total of 27 (7%) subjects experienced at least one treatment related adverse event. There were no serious adverse events related to study drug. The most frequent drug related events included dysgeusia (2.1%) and headache (2.1%).
“The data from this trial shows the strength of PyL in prostate cancer detection, and its potential to be highly valuable for disease and treatment monitoring,” said Dr. Vivien Wong, Executive Vice President of Development at Progenics. “While specificity and sensitivity are often used to describe diagnostic performance, PPV and NPV are increasingly considered more relevant indicators of actual clinical utility. Following our discussions with FDA, our Phase 3 trial design will use a primary endpoint based on PPV parameters in the biochemical recurrence setting.”
“PyL imaging holds great promise in transforming how physicians manage and treat high risk, metastatic, and recurrent prostate cancer,” said Mark Baker, Chief Executive Officer of Progenics. “Our data from OSPREY provides strong rationale for continued development, and we look forward to launching our Phase 3 trial by year-end.”
About PyL™ for PET Imaging of Prostate Cancer
PyL (also known as [18F]DCFPyL) is a fluorinated PSMA-targeted Positron Emission Topography (“PET”) imaging agent that enables visualization of both bone and soft tissue metastases to determine the presence or absence of recurrent and/or metastatic prostate cancer.
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.