A Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFv600 Mutation-Positive Patients With Metastatic or Unresectable Locally Advanced Melanoma

Not Recruiting

Trial ID: NCT02908672


This is a Phase III, double-blinded, placebo-controlled, randomized, multicenter study designed to evaluate the efficacy, safety, and pharmacokinetics of atezolizumab + cobimetinib + vemurafenib compared with placebo + cobimetinib + vemurafenib in patients with previously untreated BRAFv600 mutation-positive metastatic or unresectable locally advanced melanoma.

Official Title

A Phase III, Double-Blinded, Randomized, Placebo-Controlled Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFV600 Mutation-Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma

Stanford Investigator(s)

Sunil Arani Reddy
Sunil Arani Reddy

Clinical Associate Professor, Medicine - Oncology

Kristen N Ganjoo
Kristen N Ganjoo

Professor of Medicine (Oncology)


Inclusion Criteria:

   - Females of child bearing potential and males with female partners must and use of
   contraceptive methods with a failure rate of less than or equal to (   required during treatment and for 6 months post treatment. Males should not expose
   pregnant partners to sperm and refrain from donating sperm for 6 months post
   treatment. Women must refrain from donating eggs during this same period

   - Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc (locally
   advanced) melanoma

   - Naive to prior systemic anti-cancer therapy for melanoma (example: chemotherapy,
   hormonal therapy, targeted therapy, immunotherapy, or other biologic therapies) except
   adjuvant treatment with interferon (IFN), interleukin (IL)-2, or vaccine therapies or
   herbal therapies

   - Documentation of BRAFv600 mutation-positive status in melanoma tumor tissue (archival
   or newly obtained) through use of a clinical mutation test approved by the local
   health 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

   - Life expectancy >/=18 weeks

   - For participants not receiving therapeutic anticoagulation: International normalized
   ratio (INR) or activated partial thromboplastin time (aPTT) less than or equal to
   (   treatment

   - For participants receiving therapeutic anticoagulation: stable anticoagulant regimen
   and 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 treatment

   - Active malignancy (other than BRAFv600 mutation-positive melanoma) or malignancy
   within 3 years prior to screening are excluded, with the exception of resected
   melanoma, resected basal cell carcinoma (BCC), resected cutaneous squamous cell
   carcinoma (SCC), resected carcinoma in situ of the cervix, resected carcinoma in situ
   of the breast, in situ prostate cancer, limited-stage bladder cancer, or any other
   curatively treated malignancies from which the participant has been disease-free for
   at least 3 years

Ocular Exclusion Criteria:

   - History of or evidence of retinal pathology on ophthalmologic examination that is
   considered a risk factor for neurosensory retinal detachment, central serous
   chorioretinopathy, 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 of
   normal 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 10
   millimeter (mm) of the optic apparatus (optic nerves and chiasm); or leptomeningeal
   metastatic 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: bronchiolitis
   obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
   active 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 viral

   - 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 ovary
   cells or any component of the atezolizumab, cobimetinib, or vemurafenib formulations

   - Any grade >/=3 hemorrhage or bleeding event within 4 weeks prior to initiation of
   study treatment

   - History of stroke, reversible ischemic neurological defect, or transient ischemic
   attack within 6 months prior to initiation of study treatment


drug: Atezolizumab

drug: Atezolizumab Placebo

drug: Cobimetinib

drug: Vemurafenib

drug: Vemurafenib Placebo

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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