Um estudo de atezolizumabe mais cobimetinibe e vemurafenibe versus placebo mais cobimetinibe e vemurafenibe em pacientes previamente não tratados com mutação BRAFv600 positiva com melanoma localmente avançado metastático ou irressecável

Critérios de inclusão:

• Mulheres com potencial para engravidar e homens com parceiras devem usar métodos contraceptivos com taxa de falha menor ou igual a (
• Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc (locallyadvanced) melanoma
• Naive to prior systemic anti-cancer therapy for melanoma (example: chemotherapy,hormonal therapy, targeted therapy, immunotherapy, or other biologic therapies) exceptadjuvant treatment with interferon (IFN), interleukin (IL)-2, or vaccine therapies orherbal therapies
• Documentation of BRAFv600 mutation-positive status in melanoma tumor tissue (archivalor newly obtained) through use of a clinical mutation test approved by the localhealth authority
• Eastern Cooperative Oncology Group Performance (ECOG) Status of 0 or 1
• Measurable disease according to RECIST v1.1 (must be outside central nervous system(CNS))
• Life expectancy > /=18 semanas
• Para participantes que não receberam anticoagulação terapêutica: Índice normalizado internacional (INR) ou tempo de tromboplastina parcial ativada (aPTT) menor ou igual a(
• For participants receiving therapeutic anticoagulation: stable anticoagulant regimenand stable INR during the 28 days immediately preceding initiation of study treatment

Exclusion Criteria:

Cancer-Related Exclusion Criteria:

• Major surgical procedure within 4 weeks prior study treatment initiation
• Traumatic injury or palliative radiotherapy within 2 weeks prior study treatmentinitiation
• Active malignancy (other than BRAFv600 mutation-positive melanoma) or malignancywithin 3 years prior to screening are excluded, with the exception of resectedmelanoma, resected basal cell carcinoma (BCC), resected cutaneous squamous cellcarcinoma (SCC), resected carcinoma in situ of the cervix, resected carcinoma in situof the breast, in situ prostate cancer, limited-stage bladder cancer, or any othercuratively treated malignancies from which the participant has been disease-free forat least 3 years

Ocular Exclusion Criteria:

• History of or evidence of retinal pathology on ophthalmologic examination that isconsidered a risk factor for neurosensory retinal detachment, central serouschorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration

Cardiac Exclusion Criteria:

• History of clinically significant cardiac dysfunction
• Left ventricular ejection fraction (LVEF) below the institutional lower limit ofnormal or below 50%

Central Nervous System (CNS) Exclusion Criteria:

• Untreated or actively progressing CNS lesions (carcinomatous meningitis)
• History of metastases to brain stem, midbrain, pons, or medulla, or within 10millimeter (mm) of the optic apparatus (optic nerves and chiasm); or leptomeningealmetastatic disease; or intracranial hemorrhage

Additional Exclusion Criteria:

• Uncontrolled diabetes or symptomatic hyperglycemia
• Current severe, uncontrolled systemic disease (including, but not limited to,clinically significant cardiovascular, pulmonary, or renal disease) other than cancer
• History of malabsorption or other clinically significant metabolic dysfunction
• Pregnant or breastfeeding, or intending to become pregnant during the study
• Prior allogeneic stem cell or solid organ transplantation
• History of idiopathic pulmonary fibrosis, organizing pneumonia (example: bronchiolitisobliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence ofactive pneumonitis on screening chest computed tomography (CT) scan
• Active or history of autoimmune disease or immune deficiency
• Known clinically significant liver disease, inherited liver disease and active viraldisease
• Active tuberculosis
• Treatment with therapeutic oral or intravenous (IV) antibiotics; or with a live,attenuated vaccine; or systemic immunosuppressive medication
• Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovarycells or any component of the atezolizumab, cobimetinib, or vemurafenib formulations
• Any grade > /=3 eventos hemorrágicos ou hemorrágicos dentro de 4 semanas antes do início do tratamento do estudo
• História de acidente vascular cerebral, defeito neurológico isquêmico reversível ou ataque isquêmico transitório dentro de 6 meses antes do início do tratamento do estudo

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Código do estudo:

NCT02908672

Tipo de estudo:

Intervencional

Data de início:

janeiro / 2017

Data de finalização inicial:

outubro / 2019

Data de finalização estimada:

maio / 2024

Número de participantes:

514

Aceita voluntários saudáveis?

Não