Prostate CancerPhase 2PEM-PRONCT04565496
Phase 2 Study of Neoadjuvant PEMbrolizumab Before Radical PROstatectomy in High-risk Prostate Cancer Patients
A Phase 2 study testing Pembrolizumab in people with Prostate Cancer, run by IRCCS San Raffaele at 2 sites in Italy.
Trial summary
This is a phase 2, open-label, non-randomized, single-arm study in patients with high-risk PCa diagnosed with prostate biopsy and undergoing RP and ePLND. Pembrolizumab will be administered at the dose of 200 mg intravenously, every 3 weeks, for a total of 3 cycles prior to RP and ePLND. Read more about this study
- Who is it for?
- Ages 18 to 90 years, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesItaly
- Study dates
- 10 Apr 2023to 1 Jan 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of prostate cancer.
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- PCa detected at prostate biopsy (random biopsy with at least 12 cores taken ± target biopsy according to the mpMRI findings).
- The participant should be fit and planned for RP and ePLND (according to clinical guidelines).
- The participant should be affected by high-risk PCa defined as PSA ≥20 ng/ml and/or clinical stage ≥T3 at digital rectal examination and/or biopsy grade group 4-5.
- No evidence of lymph node invasion (cN0) and metastatic disease (M0) at imaging (mpMRI, PSMA-PET/CT and bone scan).
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- Have provided archival tumour tissue sample or newly obtained core or excisional biopsy of a tumour lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation.
- Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study treatment.
- Willingness to use contraception during study treatment
Who cannot join
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.
- Has received prior surgery or radiotherapy for PCa.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
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- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
- Has a known history of hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Has a history or current evidence of unstable cardiovascular disease
- Has a history or current evidence of congestive heart failure
- Severe hypersensitivity (Grade 3) to pembrolizumab and/or any of its excipients
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
IRCCS Ospedale San Raffaele
Milan, 20132
Ospedale San Raffaele
Milan, 20132
About this study
Official title: An Open Label, Single-arm, Phase 2 Study of Neoadjuvant PEMbrolizumab Before Radical PROstatectomy (PEM-PRO) in High-risk Prostate Cancer Patients
This is a phase 2, open-label, non-randomized, single-arm study in patients with high-risk PCa diagnosed with prostate biopsy and undergoing RP and ePLND. Pembrolizumab will be administered at the dose of 200 mg intravenously, every 3 weeks, for a total of 3 cycles prior to RP and ePLND. Local, nodal and systemic staging with prostate mpMRI, abdominal and chest CT, PSMA-PET/CT and bone scans will be performed before the administration of pembrolizumab. Surgery will be planned at the time of study inclusion to be done within 3 weeks of the last dose of study drug (screening: 3 weeks; cycle 1 followed by 3 weeks; cycle 2 followed by 3 weeks; cycle 3 followed by 3 weeks to surgery = 12 weeks from inclusion to surgery). Patients will receive 3 cycles of pembrolizumab at 200mg 3 weekly prior to RP and ePLND. Surgery will take place within 3 weeks after the last dose of the study drug. After surgery, patients with the evidence of aggressive disease features (namely, pathologic grade group 4-5; pT3b-4 and/or LNI) will be managed according to local guidelines (adjuvant radiotherapy with or without ADT will be allowed). Further Anti PD-1 therapy will not be given post-operatively. PD-L1 status will be retrospectively assessed on both tumour cells and immune cells in tissue specimens from for all patients enrolled in the study.
Read the detailed description
This is a phase 2, open-label, non-randomized, single-arm study in patients with high-risk PCa diagnosed with prostate biopsy and undergoing RP and ePLND. Screening assessments should be performed no more than 3 weeks prior to the start of study treatment. Local, nodal and systemic staging with prostate mpMRI, abdominal and chest CT, PSMA-PET/CT and bone scans will be performed before the administration of pembrolizumab. Pembrolizumab will be administered at the dose of 200 mg intravenously, every 3 weeks, for a total of 3 cycles prior to RP and ePLND. Following the screening assessment, subsequent assessments will be carried out after the 3 administrations of the study drug prior to RP and ePLND. If an unscheduled assessment is performed and the patient has not progressed, the results should be reported at the next scheduled visit. After the last cycle of pembrolizumab, mpMRI and PSMA-PET/CT scan will be performed to re-stage the tumour. Progressive disease will be defined as an increase of 20% in the maximum diameter of the index lesion at multiparametric MRI or as the onset of nodal or distant metastases at imaging or onset of symptoms and skeletal related events. In the case of symptomatic disease progression (i.e., de novo onset of symptomatic distant metastases), the patient will not complete the 3 cycles of pembrolizumab and will be considered for immediate imaging (i.e., bone scan, mpMRI and PSMA-PET/CT scan) to re-stage the tumour and for treatment according to clinical guidelines. After RP, patients will be managed according to clinical guidelines. PDL-1 status will be assessed on all samples of patients enrolled on the study. Tissue and blood samples will be collected before and after the administration of pembrolizumab. The presence of biomarkers predictive of radiological and pathological response to neoadjuvant administration of pembrolizumab will be assessed. Patients will be monitored carefully for the development of adverse events and will be monitored for clinical evidence of disease progression according to usual standards of clinical practice. Adverse events will be evaluated according to criteria outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. There will be no intrapatient dose escalation in this study. For individual patients that experience dose-limiting toxicities, no criteria for dose modification of pembrolizumab will be applied, but only criteria for dose delays as detailed in the protocol. Patients will be treated with a maximum of 3 cycles of therapy until surgery (i.e. RP and ePLND), provided that no dose-limiting toxicities will occur throughout the treatment course for each individual patient.
- Conditions
- Prostate Cancer
- Being tested
- Pembrolizumab
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Pembrolizumab will be administered at the dose of 200 mg intravenously, every 3 weeks, for a total of 3 cycles prior to RP and ePLND
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Experimental | Pembrolizumab will be administered at the dose of 200 mg intravenously, every 3 weeks, for a total of 3 cycles prior to RP and ePLND Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lymph node invasion
Reduction by 50% of the rate of lymph node invasion
Measured: 12 months
Secondary outcomes (5)
Pathologic response or presence of minimal residual disease
Absence of morphologically identifiable carcinoma in the prostatectomy specimen or the presence of minimal residual disease (i.e., ≤3 mm maximum diameter of residual tumour in the prostatectomy specimen)
Measured: 12 months
Radiological response
Radiological response will be defined as a tumour reduction of 30% in the maximum diameter of the index lesion as measured by mpMRI
Measured: 12 months
Positive surgical margins
Positive surgical margins at final pathology
Measured: 12 months
PSA persistence or early biochemical recurrence
Postoperative PSA ≥0.1 ng/ml at 6-8 weeks after surgery or two consecutive PSA values ≥0.2 ng/ml within 2 years after surgery
Measured: 36 months
Rate of adverse events
Safety
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2020
- Study start10 Apr 2023 (estimated)
- Primary completion1 Jan 2025 (estimated)
- Study completion1 Jan 2025 (estimated)
Why it stopped: Study related: Study terminated early due to protocol evolution from neoadjuvant to perioperative design, feasibility and recruitment concerns, and regulatory constraints requiring substantial amendments and additional procedures.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francesco Montorsi, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04565496
- Sponsor's protocol ID
- PEM-PRO
- Acronym
- PEM-PRO
- Status last verified
- May 2026
- First submitted
- 22 Sep 2020
- Last updated
- 15 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Single-arm, Phase 2 Study of Neoadjuvant PEMbrolizumab Before Radical PROstatectomy (PEM-PRO) in High-risk Prostate Cancer Patients
- ClinicalTrials.gov ID
- NCT04565496
- Acronym / sponsor ID
- PEM-PRO / PEM-PRO
- Conditions
- Prostate Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study related: Study terminated early due to protocol evolution from neoadjuvant to perioperative design, feasibility and recruitment concerns, and regulatory constraints requiring substantial amendments and additional procedures.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 10 Apr 2023 (estimated)
- Primary completion
- 1 Jan 2025 (estimated)
- Study completion
- 1 Jan 2025 (estimated)
- First posted
- 25 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 2, open-label, non-randomized, single-arm study in patients with high-risk PCa diagnosed with prostate biopsy and undergoing RP and ePLND. Pembrolizumab will be administered at the dose of 200 mg intravenously, every 3 weeks, for a total of 3 cycles prior to RP and ePLND. Local, nodal and systemic staging with prostate mpMRI, abdominal and chest CT, PSMA-PET/CT and bone scans will be performed before the administration of pembrolizumab. Surgery will be planned at the time of study inclusion to be done within 3 weeks of the last dose of study drug (screening: 3 weeks; cycle 1 followed by 3 weeks; cycle 2 followed by 3 weeks; cycle 3 followed by 3 weeks to surgery = 12 weeks from inclusion to surgery). Patients will receive 3 cycles of pembrolizumab at 200mg 3 weekly prior to RP and ePLND. Surgery will take place within 3 weeks after the last dose of the study drug. After surgery, patients with the evidence of aggressive disease features (namely, pathologic grade group 4-5; pT3b-4 and/or LNI) will be managed according to local guidelines (adjuvant radiotherapy with or without ADT will be allowed). Further Anti PD-1 therapy will not be given post-operatively. PD-L1 status will be retrospectively assessed on both tumour cells and immune cells in tissue specimens from for all patients enrolled in the study.
Detailed description
This is a phase 2, open-label, non-randomized, single-arm study in patients with high-risk PCa diagnosed with prostate biopsy and undergoing RP and ePLND. Screening assessments should be performed no more than 3 weeks prior to the start of study treatment. Local, nodal and systemic staging with prostate mpMRI, abdominal and chest CT, PSMA-PET/CT and bone scans will be performed before the administration of pembrolizumab. Pembrolizumab will be administered at the dose of 200 mg intravenously, every 3 weeks, for a total of 3 cycles prior to RP and ePLND. Following the screening assessment, subsequent assessments will be carried out after the 3 administrations of the study drug prior to RP and ePLND. If an unscheduled assessment is performed and the patient has not progressed, the results should be reported at the next scheduled visit. After the last cycle of pembrolizumab, mpMRI and PSMA-PET/CT scan will be performed to re-stage the tumour. Progressive disease will be defined as an increase of 20% in the maximum diameter of the index lesion at multiparametric MRI or as the onset of nodal or distant metastases at imaging or onset of symptoms and skeletal related events. In the case of symptomatic disease progression (i.e., de novo onset of symptomatic distant metastases), the patient will not complete the 3 cycles of pembrolizumab and will be considered for immediate imaging (i.e., bone scan, mpMRI and PSMA-PET/CT scan) to re-stage the tumour and for treatment according to clinical guidelines. After RP, patients will be managed according to clinical guidelines. PDL-1 status will be assessed on all samples of patients enrolled on the study. Tissue and blood samples will be collected before and after the administration of pembrolizumab. The presence of biomarkers predictive of radiological and pathological response to neoadjuvant administration of pembrolizumab will be assessed. Patients will be monitored carefully for the development of adverse events and will be monitored for clinical evidence of disease progression according to usual standards of clinical practice. Adverse events will be evaluated according to criteria outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. There will be no intrapatient dose escalation in this study. For individual patients that experience dose-limiting toxicities, no criteria for dose modification of pembrolizumab will be applied, but only criteria for dose delays as detailed in the protocol. Patients will be treated with a maximum of 3 cycles of therapy until surgery (i.e. RP and ePLND), provided that no dose-limiting toxicities will occur throughout the treatment course for each individual patient.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Drug: PembrolizumabPembrolizumab will be administered at the dose of 200 mg intravenously, every 3 weeks, for a total of 3 cycles prior to RP and ePLND |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of prostate cancer.
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- PCa detected at prostate biopsy (random biopsy with at least 12 cores taken ± target biopsy according to the mpMRI findings).
- The participant should be fit and planned for RP and ePLND (according to clinical guidelines).
- The participant should be affected by high-risk PCa defined as PSA ≥20 ng/ml and/or clinical stage ≥T3 at digital rectal examination and/or biopsy grade group 4-5.
Key exclusion criteria (19 listed)
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.
- Has received prior surgery or radiotherapy for PCa.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabPembrolizumab will be administered at the dose of 200 mg intravenously, every 3 weeks, for a total of 3 cycles prior to RP and ePLND | Drug | Pembrolizumab |
Primary outcome
Lymph node invasion
Time frame: 12 months
Reduction by 50% of the rate of lymph node invasion
5 secondary outcomes
Pathologic response or presence of minimal residual disease
Time frame: 12 months
Radiological response
Time frame: 12 months
Positive surgical margins
Time frame: 12 months
PSA persistence or early biochemical recurrence
Time frame: 36 months
Rate of adverse events
Time frame: 36 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab in people with Prostate Cancer, run by IRCCS San Raffaele at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lymph node invasion (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2026.