Resumen

The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in the adjuvant treatment of adult participants who have undergone nephrectomy and have intermediate-high risk, high risk, or M1 no evidence of disease (M1 NED) renal cell carcinoma (RCC) with clear cell component. The primary study hypothesis is that pembrolizumab is superior to placebo with respect to Disease-free Survival (DFS) as assessed by the Investigator in male and female participants with intermediate-high risk, high risk and M1 NED RCC.

Descripción detallada

Participants will be assigned to receive study treatment until disease recurrence, unacceptable adverse events (AEs), intercurrent illness that prevents further administration of treatment, Investigator's decision to withdraw the participant, noncompliance with study treatment or procedural requirements, administrative reasons requiring cessation of treatment, or until the participant has received 17 cycles of study treatment (approximately 1 year). Each cycle is 3 weeks long. With Protocol Amendment 02 (dated 04 Sep 2019), the secondary study objectives for the evaluation of pharmacokinetic (PK) parameters and the presence of pembrolizumab antidrug antibodies (ADA) were reclassified as tertiary study objectives.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Has histologically confirmed diagnosis of renal cell carcinoma (RCC) with clear cell component with or without sarcomatoid features
Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study treatment
Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study treatment through 120 days after the last dose of study treatment
Has intermediate-high risk, high risk, or M1 no evidence of disease (NED) RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status:
Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, Any Grade, N0, M0
High risk RCC: pT4, Any Grade N0, M0; pT Any stage, Any Grade, N+, M0
M1 NED RCC participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at one of the following: the time of nephrectomy (synchronous) or, ≤1 year from nephrectomy (metachronous)
Has received no prior systemic therapy for advanced RCC
Has undergone a partial nephroprotective or radical complete nephrectomy (and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants) with negative surgical margins
Must have undergone a nephrectomy and/or metastasectomy ≥28 days prior to signing informed consent and ≤12 weeks prior to randomization
Must be tumor-free as assessed by the Investigator and validated by either computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain and chest, abdomen, and pelvis and a bone scan ≤28 days from randomization
Must have provided adequate tissue per the following: Nephrectomy only: tissue from nephrectomy (required); Synchronous M1 NED: tissue from nephrectomy (required) AND, metastasectomy tissue (if available); Metachronous M1 NED: tissue from metastasectomy (required) AND, nephrectomy tissue (if available)
Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1
Has adequate organ function

Criterios de exclusión

Has had major surgery, other than nephrectomy and/or resection of pre-existing metastases for M1 NED participants, within 12 weeks prior to randomization
Has received prior radiotherapy for RCC
Has pre-existing brain or bone metastatic lesions
Has residual thrombus post nephrectomy in the vena renalis or vena cava
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 the first dose of study treatment
Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is allowed
Has a known additional malignancy that is progressing or required active treatment ≤3 years ago. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Has an active infection requiring systemic therapy
Has a history of, or is currently on, dialysis
Has a known history of human immunodeficiency virus (HIV) infection
Has known active hepatitis B or hepatitis C virus infection
Has a known history of active tuberculosis (Bacillus tuberculosis)
Has had a prior solid organ transplant
Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the Screening visit through 120 days after the last dose of study treatment
Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], OX-40, CD137 \[tumor necrosis factor receptor superfamily member 9 (TNFRSF9)\]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial
Has received prior anticancer therapy, monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before first dose of study treatment or not recovered (i.e., must be ≤ Grade 1 or at Baseline) from AEs due to previously administered agents
Has received a live vaccine within 30 days prior to the first dose of study treatment
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

Ubicaciones

Centro de Investigaciones Clinicas - Clinica Viedma ( Site 1102)

Viedma, Río Negro Province, Argentina

Sanatorio Parque ( Site 1104)

Rosario, Santa Fe Province, Argentina

Instituto de Investigaciones Metabolicas -I.D.I.M.- ( Site 1113)

Buenos Aires, Argentina

Fundacion Favaloro ( Site 1110)

Buenos Aires, Argentina

Instituto Medico Alexander Fleming ( Site 1105)

Buenos Aires, Argentina

Centro Oncologico Riojano Integral ( Site 1101)

La Rioja, Argentina

Centro Oncologico de Integracion Regional. COIR ( Site 1109)

Mendoza, Argentina

Sanatorio Britanico ( Site 1106)

Rosario, Argentina

Instituto de Oncologia de Rosario ( Site 1100)

Rosario, Argentina

Centro Medico San Roque ( Site 1108)

San Miguel de Tucumán, Argentina

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (KEYNOTE-564)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Pembrolizumab

Placebo

Ubicaciones

Centro de Investigaciones Clinicas - Clinica Viedma ( Site 1102)

Sanatorio Parque ( Site 1104)

Instituto de Investigaciones Metabolicas -I.D.I.M.- ( Site 1113)

Fundacion Favaloro ( Site 1110)

Instituto Medico Alexander Fleming ( Site 1105)

Centro Oncologico Riojano Integral ( Site 1101)

Centro Oncologico de Integracion Regional. COIR ( Site 1109)

Sanatorio Britanico ( Site 1106)

Instituto de Oncologia de Rosario ( Site 1100)

Centro Medico San Roque ( Site 1108)

Patrocinadores