The new drug application for 18F-DCFPyL is supported by results from the OSPREY and CONDOR trials.
The FDA has granted a prior review designation to a new drug application (NDA) for the PSMA-targeted PET imaging agent 18F-DCFPyL (PyL) for prostate cancer.1
The NDA is supported by data from the OSPREY and CONDOR studies. In the CONDOR study, 63.9% of men with biochemically recurrent prostate cancer who had no evidence of disease on standard-of-care imaging had a change in intended management after their 18F-DCFPyL–PET/CT scan.2
Under the Prescription Drug User Fee Act, the FDA is scheduled to make a decision on the NDA by May 28, 2021.
“We are pleased that the FDA has accepted our PyL NDA for review and granted our application priority review, which is a significant milestone for Lantheus. We believe that there is a significant unmet need for reliable, targeted imaging in prostate cancer, particularly in the high risk and biochemically recurrent populations,” Istvan Molnar, MD, chief medical officer of Lantheus (Progenics), the manufacturer of PyL stated in a press release.
The multicenter phase 3 CONDOR study enrolled men with rising PSA after definitive therapy and negative or equivocal standard-of-care imaging. Patients were required to have a PSA level ≥0.2 if they had undergone radical prostatectomy (RP) or a PSA level ≥2.0 if they were treated with radiation therapy or cryotherapy.
The primary end point was correct localization rate (CLR), defined as percentage of patients with a 1:1 correspondence between at least 1 lesion identified by PyL–PET/CT and the composite standard of truth (pathology, correlative imaging, or PSA response). PyL scans were read by 3 blinded independent central readers.
Overall, there were 208 evaluable patients, about 85% of whom underwent RP, either alone or with radiation. Median PSA level of the cohort was 0.8 ng/mL, and 68.8% had a PSA level <2.0 ng/mL. Some 27.9% had received at least 1 prior systemic therapy.
Detection of disease as manifested by a positive 18F-DCFPyL–PET/CT scan was 65.9%, 59.6%, and 59.1% by the 3 readers.
The prespecified criterion for CLR success was for the lower limit of the 95% CI to exceed 20% for at least 2 of the 3 readers. For every reader, the lower bound of the 95% CI for the CLR was well in excess of the 20% benchmark, meeting the primary end point of the study.
The CLRs were 85.6% (95% CI, 78.8%-92.3%), 87.0% (95% CI, 80.4%-93.6%), and 84.8% (95% CI, 77.8%-91.9%) by the 3 readers.
Some 64% of the evaluable patients had a change in intended management due to the scan.
In the phase 2/3 OSPREY trial, PyL was assessed in 2 patients cohorts. Cohort A included men with high-risk, locally advanced prostate cancer, and the researchers assessed the capacity of PyL to detect prostate cancer in pelvic lymph nodes. Cohort B comprised patients with metastatic or recurrent disease and the researchers examined the performance of PyL in detecting distant metastases.
In cohort A, results for PyL in detecting disease in pelvic lymph nodes showed a specificity of 96%-99%, a sensitivity of 31%-42%, and positive predictive value (PPV) of 78%-91%. The sensitivity and PPV rates for detecting metastatic lesions in cohort B were 93%-99% and 81%-88%, respectively.
Earlier this month, the FDA approved Ga 68 PSMA-11 as the first drug for PET imaging of PSMA-positive lesions in men with prostate cancer.
1. PDUFA action date of May 28, 2021 assigned by U.S. Food and Drug Administration. Published online December 9, 2021. https://bit.ly/2KtYerG. Accessed December 14, 2021.
2. Morris M, Carroll P, Saperstein L, et al. Impact of PSMA-targeted imaging with 18F-DCFPyL-PET/CT on clinical management of patients (pts) with biochemically recurrent (BCR) prostate cancer (PCa): results from a phase III, prospective, multicenter study (CONDOR). J Clin Oncol. 2020;38(15 suppl; abstr 5501). doi:10.1200/JCO.2020.38.15_suppl.5501