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A Phase II Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) and Pembrolizumab in Combination With Other Investigational Agents in Subjects With High Risk Non-muscle-Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG) Therapy - KEYNOTE 057

Studio Clinico

Patologia: Carcinoma della vescica

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: II

Richiesta mandatoria di tessuto: 

Linee di trattamento: Seconda linea, Terza/N linea

Criteri di inclusione: 

- Willing and able to provide written informed consent.
- Ability to comply with the protocol.
- Age ≥ 18 years.
- Histopathologically confirmed transitional cell carcinoma. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) transitional cell pattern.
- Fit and planned for cystectomy (according to local guidelines).
- Clinical stage T2-T4a N0 M0 disease by CT (or MRI) + PET/CT (within 4 weeks of randomization by RECIST v1.1).
- Residual disease after TURB (surgical opinion, cystoscopy or radiological presence).
- Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for testing at the study sponsor site and determined to be evaluable for tumor PD-L1 expression prior to study enrolment; patients with fewer than 15 unstained slides available at baseline (but no fewer than 10) may be eligible following discussion with Merck representatives.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Adequate hematologic and end-organ function tests.

Criteri di esclusione: 

- Patients taking regular oral steroids, above the allowed limit of 10mg/day methylprednisolone or analogues, for any reason.
- Patients must not have had steroids for 28 days prior to study entry.
- Previously intravenous chemotherapy bladder cancer. Patients who have previously had radiotherapy or concurrent chemo-radiation would be eligible.
- Malignancies other than UBC within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score ≤ 3 + 4 and PSA < 10 ng/mL undergoing active surveillance and treatment naive).
- Evidence of measurable nodal or metastatic disease.
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).
- Pregnant female patients. All female patients of childbearing potential with a positive pregnancy test within 2 weeks prior to the first dose of study treatment will be excluded from the study.
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina.
- Severe infections within 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
- Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the pembrolizumab formulation
- History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
- Patients with a history of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone.
- Patients with uncontrolled Type 1 diabetes mellitus
- Uncontrolled hypercalcemia
- Patients with prior allogeneic stem cell or solid organ transplantation.
- History of idiopathic pulmonary fibrosis
- Positive test for HIV.
- Patients with active hepatitis infection
- Patients with active tuberculosis.
- Prior treatment with anti−programmed death−1 (PD-1), or anti−PD-L1 therapeutic antibody or pathway-targeting agents.
Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study
- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrolment
History of severe immune-related adverse effects from anti−CTLA-4 (CTCAE Grade 3 and 4).
- Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.

Trattamento sperimentale: 

Participants receive pembrolizumab, 200 mg, intravenously, every 3 weeks (Q3W) for up to 24 months

Pembrolizumab coformulation
Participants receive either pembrolizumab/vibostolimab or favezelimab/pembrolizumab coformulation intravenously Q3W for up to 24 months

Trattamento di controllo: 


Obiettivi primari dello studio: 

- Complete Response Rate [ Time Frame: Up to 3 years ]
- Disease Free Survival Rate [ Time Frame: Up to 3 years ]

Obiettivi secondari dello studio: 

- Duration of Response [ Time Frame: Up to 3 years ]

Centri partecipanti

Nord Italia

IRCCS Istituto Nazionale dei Tumori
Via Venezian 1 - 20133 Milano - MI

Riferimento: Dr.ssa Valentina Guadalupi
Telefono: 0223903811


Ospedale San Raffaele di Milano
Via Olgettina 60 - 20132 Milano - MI
NB: start-up

Riferimento: Prof. Andrea Necchi

Informazioni Generali


Numero di iscrizione a registro: 2014-004026-17 / NCT02625961

Data di inserimento: 26.02.2018

Data di aggiornamento: 22.11.2023


Merck Sharp & Dohme Corp.



Principal Investigator ITALIA

Fondazione IRCCS Istituto Nazionale dei Tumori - Milano

Riferimento: Dr. Giuseppe Procopio

Telefono: 0223904450


Localita: Milano


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