Clinical Trials /

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

NCT02908672

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title:A Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFv600 Mutation-Positive Participants With 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

Clinical Trial IDs

  • ORG STUDY ID: CO39262
  • SECONDARY ID: 2016-002482-54
  • NCT ID: NCT02908672

Trial Conditions

  • Melanoma

Trial Interventions

DrugSynonymsArms
AtezolizumabATZ + Cobimetinib + Vemurafenib + Vemurafenib Placebo
Atezolizumab PlaceboATZ Placebo + Cobimetinib + Vemurafenib
CobimetinibATZ + Cobimetinib + Vemurafenib + Vemurafenib Placebo
VemurafenibATZ + Cobimetinib + Vemurafenib + Vemurafenib Placebo
Vemurafenib PlaceboATZ + Cobimetinib + Vemurafenib + Vemurafenib Placebo

Trial Purpose

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

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
ATZ + Cobimetinib + Vemurafenib + Vemurafenib PlaceboExperimentalRun-In Period (Cycle 1=28 days): Participants will receive vemurafenib 960 mg (four, 240 mg tablets) PO BID along with cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21 followed by vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 22 to 28 and vemurafenib placebo (1 tablet) PO BID on Days 22 to 28. Triple Combination Period (Cycle 2 onwards): Participants will receive ATZ 840 mg IV infusion on Day 1 and 15, cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28 of each 28-day cycle. Study treatment will continue until investigator-determined disease progression, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurs first.
  • Atezolizumab
    • Cobimetinib
    • Vemurafenib
    • Vemurafenib Placebo
ATZ Placebo + Cobimetinib + VemurafenibExperimentalRun-In Period (Cycle1=28 days): Participants will receive vemurafenib 960 milligrams (mg) (four, 240 mg tablets) orally (PO) twice a day (BID) along with cobimetinib 60 mg (three, 20 mg tablets) PO once a day (QD) on Days 1 to 21 followed by vemurafenib 960 mg (four, 240 mg tablets) PO BID on Days 22 to 28. Triple Combination Period (Cycle 2 onwards): Participants will receive ATZ placebo by intravenous (IV) infusion on Day 1 and 15, cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21, and vemurafenib 960 mg (four, 240 mg tablets) PO BID on Days 1 to 28 of each 28-day cycle. Study treatment will continue until investigator-determined disease progression, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurs first.
  • Atezolizumab
  • Atezolizumab Placebo
  • Cobimetinib
  • Vemurafenib

    Eligibility Criteria

    Inclusion Criteria:

    - Age greater than or equal to (>/=) 18 years

    - 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 (</=)1% per year is 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

    - 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

    - 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 (</=) 1.5*upper limit of normal (ULN) within 28 days prior to initiation of study 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 initiation

    - Active malignancy (other than BRAFv600 mutation-positive melanoma) or malignancy within 3 years prior to screening, 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 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:

    - 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

    - History of autoimmune disease

    - Known clinically significant liver disease, inherited liver disease and active viral disease

    - 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

    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Both
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Progression-Free Survival (PFS), as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
    Time Frame:Baseline up to disease progression or death due to any cause, whichever occurs first (up to approximately 90 months)
    Safety Issue:No
    Description:

    Secondary Outcome Measures

    Measure:Progression-Free Survival (PFS), as Determined by Independent Review Committee Using RECIST v1.1
    Time Frame:Baseline up to disease progression or death due to any cause, whichever occurs first (up to approximately 90 months)
    Safety Issue:No
    Description:
    Measure:Percentage of Participants With Objective Response, as Determined by Investigator Using RECIST v1.1
    Time Frame:Baseline up to disease progression or death due to any cause, whichever occurs first (up to approximately 90 months)
    Safety Issue:No
    Description:
    Measure:Duration of Response, as Determined by Investigator Using RECIST v1.1
    Time Frame:Baseline up to disease progression or death due to any cause, whichever occurs first (up to approximately 90 months)
    Safety Issue:No
    Description:
    Measure:Overall Survival
    Time Frame:Baseline up to death due to any cause (up to approximately 90 months)
    Safety Issue:No
    Description:
    Measure:Percentage of Participants Who are Alive at Year 2
    Time Frame:2 years
    Safety Issue:No
    Description:
    Measure:Time to Deterioration in Global Health Status Using The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) Global Health Status Scale Score
    Time Frame:Baseline up to end of treatment (approximately 90 months)
    Safety Issue:No
    Description:
    Measure:Time to Deterioration in Physical Functioning Using EORTC QLQ-30 Physical Functioning Scale Score
    Time Frame:Baseline up to end of treatment (approximately 90 months)
    Safety Issue:No
    Description:
    Measure:Percentage of Participants with Adverse Events and Serious Adverse Events
    Time Frame:Baseline up to 6 months after the last dose of study treatment (approximately 90 months)
    Safety Issue:No
    Description:
    Measure:Serum Concentration of ATZ
    Time Frame:Pre-infusion (0 hour) and 30 minutes (min) post-infusion (infusion duration=30-60 min) on Day 1 (D1) of Cycles (Cy) 1-4; Pre-infusion on D1 of Cy 8 & every 8 Cy thereafter up to ATZ discontinuation (approximately 90 months overall) (1 Cy=28 days)
    Safety Issue:No
    Description:
    Measure:Plasma Concentration of Cobimetinib
    Time Frame:Pre-dose (0 hour) and 3 to 6 hours post dose on Day 15 of Cy 1 and 4 (1 Cy = 28 days)
    Safety Issue:No
    Description:
    Measure:Plasma Concentration of Vemurafenib
    Time Frame:Pre-dose (0 hour) and 3 to 6 hours post dose on Day 15 of Cy 1 and 4 (1 Cy = 28 days)
    Safety Issue:No
    Description:
    Measure:Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab
    Time Frame:Pre-infusion (0 hour) on D1 of Cy 1-4; Pre-infusion on D1 of Cy 8 & every 8 Cy thereafter up to atezolizumab discontinuation (approximately 90 months overall) (1 Cy=28 days) (approximately up to 90 months)
    Safety Issue:Yes
    Description:

    Trial Keywords