Phase 2 Study of Neoadjuvant PEMbrolizumab Before Radical PROstatectomy in High-risk Prostate Cancer Patients

NCT04565496 | Withdrawn Phase 2 DMC

• 1 other identifier: PEM-PRO
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Lymph node invasion

  Reduction by 50% of the rate of lymph node invasion

  12 months

Secondary Outcomes (5)

• Pathologic response or presence of minimal residual disease

  12 months

• Radiological response

  12 months

• Positive surgical margins

  12 months

• PSA persistence or early biochemical recurrence

  36 months

• Rate of adverse events

  36 months

Study Arms (1)

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

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

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

Pembrolizumab

Eligibility Criteria

• Age: 18 Years - 90 Years
• Gender Eligibility Details: Patients affected by prostate cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (2)

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 22, 2020
• First Posted: September 25, 2020
• Study Start: April 10, 2023
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: May 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)