Study Design
OSPREY COHORT A1
OSPREY was a robust, prospective, multicenter, phase 2/3 clinical trial of 385 patients. In Cohort A, 268 men with high-risk prostate cancer had evaluable histopathology for determining the diagnostic performance of PYLARIFY in identifying pelvic nodal metastases
OSPREY Cohort A assessed sensitivity, specificity, PPV, and NPV in pelvic lymph nodes and in the prostate gland for PSMA-targeted PET with PYLARIFY
Patient population
268 patients with high-risk PCa (clinical stage ≥T3a, PSA >20 ng/mL, or Gleason score ≥8 with planned RP-PLND). Patients with prior androgen deprivation therapy or any investigational neoadjuvant agent or intervention were excluded1,2
PSMA-targeted PET scan with PYLARIFY
A single dose of PYLARIFY 9 mCi (333 MBq) IV, followed by PET/CT after 1-2 hours. Patients voided prior to imaging, and PET and non-contrast low-dose CT images were acquired from the mid thigh through the skull vertex
Evaluation
252 patients underwent surgery and had PLND evaluated locally by pathologists blinded to the imaging results. 16 patients did not undergo RP-PLND and were excluded from the primary analysis. All PYLARIFY scans were submitted for central imaging review by 3 blinded independent board-certified nuclear medicine physicians
Co-primary endpoints:
- Specificity
- Sensitivity
Secondary endpoints:
- PPV
- Detection of M1 disease
- NPV
- Detection of primary tumor within the prostate
In COHORT A, OSPREY included high-risk patients across a broad range of PSA levels, disease stages, age ranges, and Gleason scores*
|
Median age (range) |
|
|---|---|
|
65 (46-84) |
|
|
Race and ethnicity |
|
|
White |
86.9% |
|
Black or African American |
8.6% |
|
Hispanic |
4.1% |
|
Asian |
2.6% |
|
Other |
0.7% |
|
Regional lymph node (N) stage, AJCC† |
|
|
NX |
38.4% |
|
N0 |
58.2% |
|
N1 |
3.4% |
|
Primary tumor (T) stage, AJCC† |
|
|---|---|
|
TX |
3% |
|
T1a |
0.4% |
|
T1b |
0.7% |
|
T1c |
32.5% |
|
T2 |
2.6% |
|
T2a |
16.8% |
|
T2b |
11.2% |
|
T2c |
5.2% |
|
T3 |
1.1% |
|
T3a |
20.9% |
|
T3b |
5.2% |
|
T4 |
0.4% |
|
Distance metastases (M) stage, AJCC† |
|
|---|---|
|
Mx |
17.9% |
|
M0 |
80.6% |
|
M1 |
0.4% |
|
M1a |
0% |
|
M1b |
0.4% |
|
M1c |
0% |
|
Median PSA (ng/mL), (range) |
|
|
9.7 (1.2-125.3) |
|
|
Total Gleason score |
|
|
6 |
1.1% |
|
7 |
18.3% |
|
8 |
44.8% |
|
9 |
34.3% |
|
10 |
1.5% |
Study Design
CONDOR3
CONDOR was a robust, multicenter, phase 3 trial of 208 patients with suspected recurrent or metastatic prostate cancer with negative or equivocal results using standard imaging
CONDOR assessed correct localization rate (CLR)—a metric of diagnostic performance measuring PPV enhanced with anatomic lesion matching—in patients with biochemically recurrent (BCR) prostate cancer
Patient population
208 patients with biochemically recurrent prostate cancer, defined as rising PSA ≥0.2 ng/mL after RP or ≥2 ng/mL above nadir after RT. All patients had negative/equivocal findings for prostate cancer on standard imaging 60 days before receiving PYLARIFY
Exclusion criteria included administration of any high-energy (>300 KeV) gamma-emitting radioisotope within five physical half-lives prior to PYLARIFY injection, androgen deprivation therapy (ADT) within 3 months of imaging, investigational therapy for prostate cancer within 60 days of imaging, and ongoing systemic therapy
PSMA-targeted PET scan with PYLARIFY
A single dose of PYLARIFY 9 mCi (333 MBq) IV 1-2 hours before PET/CT
Patients voided prior to imaging, and PET and non-contrast low-dose CT images were acquired from the mid thigh through the skull vertex
Evaluation
208 underwent a PYLARIFY scan. PYLARIFY assessment was performed by 3 independent, blinded, board-certified nuclear medicine physicians. Patients with positive scans were scheduled for follow-up to verify suspected lesions based on a composite standard of truth (SOT)
Primary endpoint:
CLR of PYLARIFY
CLR is computed as 100 X TP/(TP+FP), where TP = true-positive result and FP = false-positive result for each central imaging reader*
Secondary endpoint:
Percentage of patients with a change in intended treatment plan based on pre- and post-medical management questionnaires (MMQs) completed by treating investigators. MMQs were available for 205 out of 208 patients
Reference standards of truth in CONDOR
Because most patients were not expected to have an amenable lesion for histological verification, a composite standard of truth was agreed to with the FDA based on these reference standards (in order of priority):
-
01
Evaluable histopathology results from prostatectomy, salvage pelvic lymph node dissection, or targeted biopsy
-
02
Correlative follow-up imaging findings using ¹⁸F-fluciclovine or ¹¹C-choline PET, or focused MRI or CT
-
03
If neither of the above was available or informative, confirmed PSA response* up to 9 months post-radiation initiation (without concomitant ADT) of all PET-positive foci
CONDOR included BCR patients with a broad range of PSA levels and Gleason scores ranging from 6-9
|
Median age (range) |
|
|---|---|
|
68 (43-91) |
|
|
Patients ≥65 years old |
|
|
67.8% |
|
|
Median months from PCa diagnosis (range) |
|
|
71 (3-356) |
|
|
Prior prostate cancer therapies |
|
|
Radical prostatectomy only |
49.5% |
|
Radiation therapy only |
14.9% |
|
Radical prostatectomy and radiation therapy |
35.6% |
|
At least 1 prior systemic therapy |
27.9% |
|
Gleason score |
|
|---|---|
|
<8 |
73.6% |
|
≥8 |
26.4% |
|
PSA (ng/mL): Median (range) 0.8 (0.17-98.45) |
|
|
<0.5 |
34.2% |
|
0.5-<1.0 |
18.3% |
|
1.0-<2.0 |
16.3% |
|
2.0-<5.0 |
16.3% |
|
≥5.0 |
14.9% |
Study Design
OSPREY COHORT B1
OSPREY was a robust, prospective, multicenter, phase 2/3 clinical trial of 385 patients. Cohort B assessed sensitivity and PPV in 117 patients with radiologic evidence of recurrence
Patient population
117 patients with radiologic evidence of local recurrence or evidence of metastatic disease on conventional imaging*
Exclusion criteria included prior radiation or ablative therapy to intended site of biopsy if within the prostate bed and initiation of new therapy for recurrent and/or progressive metastatic disease since radiographic documentation of recurrence/progression1,2
Baseline conventional imaging
CT, MRI, or bone scan 4-6 weeks before PYLARIFY PET/CT
PSMA-targeted PET scan with PYLARIFY
A single dose of PYLARIFY 9 mCi (333 MBq) IV, followed by PET/CT after 1-2 hours
Evaluation
Lesions (biopsy) detected by conventional imaging, evaluated for presence or absence of PCa, other neoplasm, or deemed unevaluable
Secondary endpoints:
- Sensitivity†
- PPV
INDICATION
PYLARIFY (piflufolastat F 18) Injection is a radioactive diagnostic agent indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer:
- with suspected metastasis who are candidates for initial definitive therapy.
- with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.
IMPORTANT SAFETY INFORMATION
Contraindications
None.
Warnings and Precautions
Risk of Image Misinterpretation
Imaging interpretation errors can occur with PYLARIFY imaging. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. The performance of PYLARIFY for imaging of patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels. The performance of PYLARIFY for imaging of metastatic pelvic lymph nodes prior to initial definitive therapy seems to be affected by risk factors such as Gleason score and tumor stage. PYLARIFY uptake is not specific for prostate cancer and may occur with other types of cancer as well as non-malignant processes and in normal tissues. Clinical correlation, which may include histopathological evaluation of the suspected prostate cancer site, is recommended.
Hypersensitivity Reactions
Monitor patients for hypersensitivity reactions, particularly patients with a history of allergy to other drugs and foods. Reactions may be delayed. Always have trained staff and resuscitation equipment available.
Radiation Risks
Diagnostic radiopharmaceuticals, including PYLARIFY, expose patients to radiation. Radiation exposure is associated with a dose-dependent increased risk of cancer. Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure. Advise patients to hydrate before and after administration and to void frequently after administration.
Adverse Reactions
The most frequently reported adverse reactions were headaches, dysgeusia and fatigue, occurring at rate of ≤2% during clinical studies with PYLARIFY. In addition, a delayed hypersensitivity reaction was reported in one patient (0.2%) with a history of allergic reactions.
Drug Interactions
Androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of PYLARIFY in prostate cancer. The effect of these therapies on performance of PYLARIFY PET has not been established.
To report suspected adverse reactions for PYLARIFY, call 1-800-362-26681-800-362-2668 or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
For important risk and use information about PYLARIFY Injection, please see Full Prescribing information.
INDICATION
PYLARIFY (piflufolastat F 18) Injection is a radioactive diagnostic agent indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer:
- with suspected metastasis who are candidates for initial definitive therapy.
- with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.
PYLARIFY (piflufolastat F 18) Injection is a radioactive diagnostic agent indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer:
- with suspected metastasis who are candidates for initial definitive therapy.
- with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.
IMPORTANT SAFETY INFORMATION
Contraindications
None.
Warnings and Precautions
Risk of Image Misinterpretation
Imaging interpretation errors can occur with PYLARIFY imaging. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. The performance of PYLARIFY for imaging of patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels. The performance of PYLARIFY for imaging of metastatic pelvic lymph nodes prior to initial definitive therapy seems to be affected by risk factors such as Gleason score and tumor stage. PYLARIFY uptake is not specific for prostate cancer and may occur with other types of cancer as well as non-malignant processes and in normal tissues. Clinical correlation, which may include histopathological evaluation of the suspected prostate cancer site, is recommended.
Hypersensitivity Reactions
Monitor patients for hypersensitivity reactions, particularly patients with a history of allergy to other drugs and foods. Reactions may be delayed. Always have trained staff and resuscitation equipment available.
Radiation Risks
Diagnostic radiopharmaceuticals, including PYLARIFY, expose patients to radiation. Radiation exposure is associated with a dose-dependent increased risk of cancer. Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure. Advise patients to hydrate before and after administration and to void frequently after administration.
Adverse Reactions
The most frequently reported adverse reactions were headaches, dysgeusia and fatigue, occurring at rate of ≤2% during clinical studies with PYLARIFY. In addition, a delayed hypersensitivity reaction was reported in one patient (0.2%) with a history of allergic reactions.
Drug Interactions
Androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of PYLARIFY in prostate cancer. The effect of these therapies on performance of PYLARIFY PET has not been established.
To report suspected adverse reactions for PYLARIFY, call 1-800-362-26681-800-362-2668 or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
For important risk and use information about PYLARIFY Injection, please see Full Prescribing information.
Contraindications
None.
Warnings and Precautions
Risk of Image Misinterpretation
Imaging interpretation errors can occur with PYLARIFY imaging. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. The performance of PYLARIFY for imaging of patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels. The performance of PYLARIFY for imaging of metastatic pelvic lymph nodes prior to initial definitive therapy seems to be affected by risk factors such as Gleason score and tumor stage. PYLARIFY uptake is not specific for prostate cancer and may occur with other types of cancer as well as non-malignant processes and in normal tissues. Clinical correlation, which may include histopathological evaluation of the suspected prostate cancer site, is recommended.
Hypersensitivity Reactions
Monitor patients for hypersensitivity reactions, particularly patients with a history of allergy to other drugs and foods. Reactions may be delayed. Always have trained staff and resuscitation equipment available.
Radiation Risks
Diagnostic radiopharmaceuticals, including PYLARIFY, expose patients to radiation. Radiation exposure is associated with a dose-dependent increased risk of cancer. Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure. Advise patients to hydrate before and after administration and to void frequently after administration.
Adverse Reactions
The most frequently reported adverse reactions were headaches, dysgeusia and fatigue, occurring at rate of ≤2% during clinical studies with PYLARIFY. In addition, a delayed hypersensitivity reaction was reported in one patient (0.2%) with a history of allergic reactions.
Drug Interactions
Androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of PYLARIFY in prostate cancer. The effect of these therapies on performance of PYLARIFY PET has not been established.
To report suspected adverse reactions for PYLARIFY, call 1-800-362-26681-800-362-2668 or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
For important risk and use information about PYLARIFY Injection, please see Full Prescribing information.
References
- Pienta KJ, Gorin MA, Rowe SP, et al. A phase 2/3 prospective multicenter study of the diagnostic accuracy of prostate specific membrane antigen PET/CT with 18F-DCFPyL in prostate cancer patients (OSPREY). J Urol. 2021;206(1):52-61.
- ClinicalTrials.gov. Study NCT02981368: Study of 18F-DCFPyL PET/CT imaging in patients with prostate cancer (OSPREY). Accessed March 27, 2025. https://clinicaltrials.gov/study/NCT02981368
- Morris MJ, Rowe SP, Gorin MA, et al. Diagnostic performance of 18F-DCFPyL-PET/CT in men with biochemically recurrent prostate cancer: results from the CONDOR phase III, multicenter study. Clin Cancer Res. 2021;27(13):3674-3682.
