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

• Register: ClinicalTrials.gov
• Last refreshed on: 1 April 2024
• Main ID: NCT02908672
• Date of registration: 19/09/2016
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: 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
• Scientific 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
• Date of first enrolment: January 13, 2017
• Target sample size: 514
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02908672
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Australia, Austria, Belgium, Brazil, Canada, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Netherlands, New Zealand, Poland, Portugal, Russian Federation, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

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
(CNS))

- 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
initiation

- 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
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

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Melanoma

Intervention(s)

Drug: Cobimetinib

Drug: Atezolizumab Placebo

Drug: Vemurafenib

Drug: Atezolizumab

Drug: Vemurafenib Placebo

Primary Outcome(s)

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 33 months)]

Secondary Outcome(s)

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 33 months)]

Overall Survival [Time Frame: Baseline up to disease progression or death due to any cause, whichever occurs first (up to approximately 33 months)]

Plasma Concentration of Cobimetinib Dose: 60 mg [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)]

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 33 months)]

Plasma Concentration of Cobimetinib Dose: 20/40 mg [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)]

Time to Deterioration in Global Health Status Using The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Scale Score [Time Frame: Baseline up to disease progression or death due to any cause, whichever occurs first (up to approximately 33 months)]

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 33 months)]

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)]

Serum Concentration of Atezolizumab [Time Frame: Pre-infusion Day 1 of Cycles 1-4; 30 minutes post-infusion Day 1 of Cycles 1 and 4; at Atezolizumab discontinuation (up to approximately 33 months)(1 Cycle = 28 days)]

Time to Deterioration in Physical Functioning Using EORTC QLQ-C30 Physical Functioning Scale Score [Time Frame: Baseline up to disease progression or death due to any cause, whichever occurs first (up to approximately 33 months)]

Percentage of Participants Positive for Anti-Drug Antibodies (ADA) to Atezolizumab [Time Frame: Pre-infusion Day 1 of Cycles 1-4; at Atezolizumab discontinuation (up to approximately 90 months)(1 Cycle=28 days) (approximately up to 33 months)]

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 33 months)]

Percentage of Participants Who Have Survived at 2 Years [Time Frame: 2 years]

Secondary ID(s)

2016-002482-54

CO39262

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 19/11/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02908672