A prospective, Phase 3, multi center, single-arm, imaging study investigating the safety and diagnostic performance of rhPSMA 7.3 (18F) PET ligand in men with suspected prostate cancer recurrence based on elevated PSA following prior therapy

Prostate cancer is one of the most common cancers in men. Recurrence (return)
of prostate cancer is also common. One of the ways doctors detect recurrence is
by measuring PSA levels in your blood. However, an increase in PSA levels alone
does not tell the doctor where the cancer is or how much cancer there is.
Imaging tests, like a bone scan, magnetic resonance imaging (MRI) and/or
computed tomography (CT), are often performed to help the doctor determine
where or how much cancer there is, and how best to treat the cancer.
This study looks at the ability of the study agent, used along with a PET scan,
to guide your doctor in deciding the best treatment for you. The study agent
binds to a protein called prostate specific membrane antigen (PSMA) that is
found on the surface of cancer cells. The amount of this protein is known to be
increased in prostate cancer. PET imaging helps to measure how the tracer
attaches to this protein and the build up of the protein. Therefore, the study
agent used together with a PET scan may help to detect sites where there is
cancer and where it has spread.

To assess the patient level CDR and region level PPV of rhPSMA-7.3 (18F) PET
for BCR of PCa using histopathology or imaging as a SoT.
Secondary Objectives:
1. To assess the patient level CDR and region level PPV of rhPSMA-7.3 (18F) PET
in the subgroup of patients who have negative baseline conventional imaging.
2. To assess the patient level CDR and region level PPV of rhPSMA-7.3 (18F) PET
separated into subgroups of patients with reference standard histopathology
available and unavailable.
3. To assess the patient level CDR and region level PPV of rhPSMA-7.3 (18F) PET
stratified by PSA level.
4. To assess the CDR of rhPSMA-7.3 (18F) PET on a region level.
5. To assess the impact of rhPSMA 7.3 (18F) PET imaging results on the intended
clinical management of study participants using a clinician survey.
6. To assess the inter- and intra reader agreement of rhPSMA-7.3 (18F) scan
interpretation by the blinded independent readers.
7. To assess the safety of rhPSMA 7.3 (18F) injection in patients.
Exploratory objectives:
1. To assess the overall detection rate (without SoT confirmation) on a patient
level and including all subgroup analyses listed in Secondary Endpoints 1-4
above.
2. To assess the patient level PPV in which a TP patient is defined as having
at least one TP region, regardless of any coexisting FP regions.
3. To assess any incremental rhPSMA-7.3 (18F) PET findings (e.g. more sites of
involvement) compared to conventional imaging.
4. To assess the impact of rhPSMA 7.3 (18F) PET on upstaging patients with BCR
of PCa a) post radical prostatectomy (RP) or b) post radiation therapy (RT)
compared to conventional imaging.
5. To assess patient and regional level detection rates of rhPSMA 7.3 (18F) PET.
6. To assess patient and regional level detection rates of rhPSMA 7.3 (18F) PET
as a function of PSA, prior Gleason score, and PSA doubling time (PSAdt) in a)
post-RP or b) post RT patients.

This is a prospective, Phase 3, multi center, single-arm, single dose study
designed to evaluate the safety and diagnostic performance of radiohybrid
prostate specific membrane antigen (rhPSMA) 7.3 (fluorine-18 [18F]) positron
emission tomography (PET) ligand for imaging in men with suspected biochemical
recurrence (BCR) of prostate cancer (PCa) based on elevated prostate specific
antigen (PSA) following prior therapy.
A number of measures have now been put in place to streamline the study for
patients* safety due to the continued impact of the Corona Virus Disease 19
(COVID-19) pandemic on daily life.
Patients with a diagnosis of BCR of PCa being worked up for re staging and
eligible for potential salvage treatment will be consented and enrolled. After
enrollment (either before or after conventional imaging if not already
completed), patients will receive 8 mCi (296 MBq) ± 20% rhPSMA 7.3 (18F),
delivered as an intravenous (IV) bolus injection, followed by PET imaging.
If feasible, the patient will undergo image-guided biopsy of a PET-positive
lesion(s) suspicious for recurrence of PCa within 45 days following rhPSMA 7.3
(18F) PET imaging. Note: due to the COVID-19 pandemic, this may be extended up
to 60 days.
If necessary, confirmatory imaging (for Standard of Truth [SoT]) will be
performed within 45 days following rhPSMA-7.3 (18F) PET imaging or attempted
biopsy and, if necessary, additional follow up confirmatory imaging may be
performed up to 90 days after rhPSMA-7.3 (18F) PET. Patients may receive
salvage treatment following further consultation with their physician (outside
of the scope of this study). The salvage treatment prescribed will be recorded.
If treatment consists of a surgical resection, the histology obtained will be
correlated with rhPSMA 7.3 (18F) PET imaging. (and will serve as the SoT for
PET-positive lesions resected). Follow-up confirmatory imaging, as part of the
SoT algorithm, should not delay the patient*s treatment.
Notes: due to the COVID-19 pandemic, biopsy and surgical procedures performed
to obtain SoT histology and initial confirmatory imaging assessments (in
patients not undergoing biopsy/resection) may be delayed up to Day 60 to ensure
the safety (i.e., decreased potential exposure to severe acute respiratory
syndrome coronavirus 2 [SARS-CoV-2]) of enrolled patients. In patients with
multiple PET-positive regions, confirmation of at least one PET positive lesion
in each region is required either by biopsy/surgical resection or confirmatory
imaging.
Safety (adverse events [AEs] and vital signs) will be monitored during the
study.

What participation involves
If you are eligible for the study and give your consent, some standard imaging
procedures like a bone scan, MRI and/or CT will be done.
The exact duration of your participation could vary depending on the procedures
that will be performed to confirm the spread of cancer, but it will not exceed
90 days from the date of the study scan.

Screening
First we determine whether you can participate. Then you will be asked to sign
this consent form if you agree to take part in this study.
The following assessment and procedures will take place during screening:
• All details of your participation in the study will be recorded into a study
database as well as your patient records.
• Details such as your date of birth and gender will be noted in the study
database. Your height and weight will be measured.
• You will be asked about your medical history including a history of when
prostate cancer was first diagnosed and any previous prostate cancer
treatments. Other laboratory reports or scan reports performed by your doctor
to investigate your prostate cancer will be reviewed.
• You will be asked about any medicines that you are currently taking.
• Your vital signs (blood pressure, pulse, respiration rate, and temperature)
will be measured.
• Standard imaging like bone scan, CT scan or MRI of the pelvic and stomach
area and a chest CT may be performed at this screening visit if the previous
scans were taken at least 90 days before Screening. If the standard imaging is
not done at or before Screening, it may be done within 2 weeks of Visit 2.
Sometimes we find something not associated with Prostate Cancer during the scan
that requires further medical investigation. We will always tell you. Further
investigation is carried out by the primary care physician or specialist. The
cost of this will be borne by your own insurance.
If the study doctor decides that you are not eligible to take part in this
study, he/she will tell you and discuss with you further treatment options for
your condition outside of this study.
Treatment
Study Agent Administration
On the day of the study PET scan, the study staff will place an intravenous
(IV) catheter (a long, thin tube) into a vein in your arm. The study agent will
be administered through this tubing. The PET imaging will be done between 50 to
90 minutes after the study agent is injected.
PET Scan
PET imaging produces detailed 3-dimensional images of the inside of the body.
In this study, it works by detecting the radiation given off by the study agent
injected into your arm.
During the scan, you will lie on your back on the scanning bed, preferably with
your arms rested above your head. The bed will move slowly through the PET
scanner. The PET scan is used in combination with a CT scan. The CT portion of
the scan usually takes about 1 minute. The PET portion of the scan usually
takes about 20 minutes.
Visits and Tests
For the study, after the screening visit, you have to visit the hospital 2
times (visit 2 and 3) in 45 days. A visit will take 1-4 hours.
During these visits, most of the procedures from the screening will be
repeated. In addition, the following will take place:


Visit 2
• Any change in the medications from the Screening Visit will be noted.
• Before the PET scan, your weight, and vital signs (blood pressure, pulse,
respiration rate, and temperature) will be measured.
• You will be asked about any side effects or changes in your health since your
last visit.
• You will be administered the study agent in a safe and correct manner as
described earlier in this document.
• Your vital signs will be measured again after the PET scan.
• You will undergo a PET scan as described earlier in this document.
• Your Visit 3 will be booked within 7 days.
Visit 3
• You will be asked about any side effects or changes in your health that you
have had since your last visit and any changes to or new medicines you are
taking.
• Your imaging results will be discussed with you and if required further
procedures will be scheduled. If the results of the PET scan do not show
suspicions of the cancer coming back, then you will finish the study at this
visit. If there are findings on the PET scan you will remain in the study until
reports from tissue biopsies and/or other imaging tests are obtained to confirm
the location and extent of cancer.
Follow-up Procedures
• If there appears to be a cancerous lesion on the PET scan, a sample of tissue
(biopsy) from the area may be taken for testing to confirm the spread of cancer.
• If you have a planned surgery, then the study doctor will note the date of
the surgery. The doctor may also request results of the tests which were
performed on the tissue that is removed during the surgery.
• Other scanning tests such as an ultrasound, a CT scan or an MRI may also be
ordered by your doctor.
• You will be asked about any side effects or changes in your health since your
last visit and any changes to or new medicines you are taking.
*
Secondary Follow-up Procedures
• If needed, further standard imaging tests will be done to confirm the results
of the PET scan. However, this will not delay or affect your cancer treatment.
• If you have had a surgery after your last appointment, then your study doctor
will compare the results of the tests done which was performed on the tissue
removed during the surgery with the results of your PET scan.
• The study doctor will also note if you are undergoing any other cancer
treatment after the PET scan visit.
• You will be asked about any side effects or changes in your health since your
last visit and any changes to or new medicines you are taking

Possible side effects and discomforts
The new diagnostic study agent may have side effects and may involve unknown
risks. Any medication or procedure can have temporary and permanent side
effects and can cause unforeseen adverse reactions.

Possible risks related to the study agent
The study agent has already been given to both men with prostate cancer and
healthy volunteers and there have been very few side effects. There have been
no reported side effects considered to be directly related to the study agent.
There may be side effects that are not known at this time.

Possible risks related to study procedures.
• Radiation: This study involves exposure to a small amount of radiation from
the study agent. Radiation is part of our natural environment. We are exposed
to background radiation from materials in the earth itself, from naturally
occurring radon in the air, from outer space, and from inside our own bodies
(as a result of the food and water we consume). You will be exposed to
radiation from the study agent. The total radiation burden in this study is
approximately 8 mSv (Milli-Sievert is the unit of measurement for the radiation
dose) from the main study examination (study agent and PET/CT scan). In
comparison, the background radiation in the Netherlands is ~2.5 mSv, per year.
If you often participate in scientific research with a radiation burden, you
should discuss with the investigator whether participation at this time is
sensible. The radiation used during the study may cause damage to your health.
The main risk associated with all radiation exposure is the possibility of
developing a radiation-induced cancer later in life. At these exposure levels,
the risk is small. We advise you not to participate in another scientific study
with a radiation burden in the near future. There is no objection to research
or treatment with radiation for medical reasons.
• PET Scan: You may feel uncomfortable during the tests, since you are not
allowed to move during the imaging procedure, and you may feel frightened by
the cramped space in

The new diagnostic study agent may have side effects and may involve unknown
risks. Any medication or procedure can have temporary and permanent side
effects and can cause unforeseen adverse reactions.

Possible risks related to the study agent
The study agent has already been given to both men with prostate cancer and
healthy volunteers and there have been very few side effects. There have been
no reported side effects considered to be directly related to the study agent.
There may be side effects that are not known at this time.

Possible risks related to study procedures.
• Radiation: This study involves exposure to a small amount of radiation from
the study agent. Radiation is part of our natural environment. We are exposed
to background radiation from materials in the earth itself, from naturally
occurring radon in the air, from outer space, and from inside our own bodies
(as a result of the food and water we consume). You will be exposed to
radiation from the study agent. The total radiation burden in this study is
approximately 8 mSv (Milli-Sievert is the unit of measurement for the radiation
dose) from the main study examination (study agent and PET/CT scan). In
comparison, the background radiation in the Netherlands is ~2.5 mSv, per year.
If you often participate in scientific research with a radiation burden, you
should discuss with the investigator whether participation at this time is
sensible. The radiation used during the study may cause damage to your health.
The main risk associated with all radiation exposure is the possibility of
developing a radiation-induced cancer later in life. At these exposure levels,
the risk is small. We advise you not to participate in another scientific study
with a radiation burden in the near future. There is no objection to research
or treatment with radiation for medical reasons.
• PET Scan: You may feel uncomfortable during the tests, since you are not
allowed to move during the imaging procedure, and you may feel frightened by
the cramped space inside the machine.
• Blood draw/IV insertion: You will be asked to give blood samples during this
study. When blood samples are taken from a vein, there is a risk of bruising,
discomfort and pain at the site. Sometimes a person may become dizzy or faint
when blood is drawn and there is a rare possibility of infection.
• Delay in treatment: Depending on the results of the images, your study doctor
may need to take a biopsy or schedule additional imaging as part of this study
and your treatment may be delayed until these are completed. Treatment will not
be delayed any longer than 45 days after the PET Scan.
• Biopsy: A biopsy involves taking a small sample of body tissue, so it can be
examined under a microscope. Most biopsies will only require local anesthetic,
which means you will not need to stay in hospital overnight. But an overnight
stay is may be required when the procedure is carried out under general
anesthetic. Most types of biopsy are painless once the anesthetic starts to
work, although this depends on where the sample is taken from. You may
experience a dull ache, which can be treated with pain medication on the advice
of your doctor. You may need to have stitches, or a dressing applied before you
leave.
• Additional imaging: If a biopsy cannot be taken or if the biopsy failed to
produce a reliable result, additional imaging may be required. Additional
imaging may consist of
o CT scan: A CT scan is a type of X-ray. In some cases, a contrast medium may
be needed. There is a risk of allergies to the contrast medium.
o MRI: Magnetic resonance imaging is a type of scan that uses magnetic fields
and radio waves to take a picture of the body part being scanned. MRI machines
produce loud banging noises, which cause some people to become stressed or
upset. You may also feel uncomfortable inside the magnet if you do not like to
be inside small places.
o PET Scan with a different radiotracer. You are not allowed to move during the
imaging procedure, and you may feel uncomfortable by the cramped space inside
the machine.
• New findings: In a small percentage of men scanned for prostate cancer the
PET scan has detected other (non-prostate cancers) which were not suspected at
the time of scanning. This could provide useful information but may also result
in additional stress or anxiety.