A Study of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Participants With Previously Untreated Advanced BRAFv600 Wild-Type Melanoma

Not Recruiting

Trial ID: NCT03273153

Purpose

This is a Phase III, multicenter, open-label, randomized study designed to evaluate the efficacy, safety, and pharmacokinetics of cobimetinib plus atezolizumab compared with pembrolizumab in treatment-naive participants with advanced BRAFV600 wild-type melanoma.

Official Title

A Phase III, Open-Label, Multicenter, Two Arm, Randomized Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Patients With Previously Untreated Advanced BRAF V600 Wild-Type Melanoma

Stanford Investigator(s)

Sunil Arani Reddy
Sunil Arani Reddy

Clinical Associate Professor, Medicine - Oncology

Eligibility


Inclusion Criteria:

Disease-Specific Inclusion Criteria

   - Histologically confirmed locally advanced and unresectable or metastatic melanoma

   - Naive to prior systemic anti-cancer therapy for melanoma

   - Documentation of BRAFV600 wild-type status in melanoma tumor tissue through use of a
   clinical mutation test approved by the local health authority

   - A representative, formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a
   paraffin block (preferred) or 20 slides containing unstained, freshly cut, serial
   sections must be submitted along with an associated pathology report prior to study
   entry. If 20 slides are not available or the tissue block is not of sufficient size,
   the patient may still be eligible for the study, after discussion with and approval by
   the Medical Monitor

   - Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
   v1.1

   - Age >=18 years at time of signing Informed Consent Form

   - Ability to comply with the study protocol, in the investigator's judgment

   - Histologically or cytologically confirmed BRAFV600 wild-type melanoma

   - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

   - Life expectancy >=3 months

   - Adequate hematologic and end-organ function

   - For women of childbearing potential: agreement to remain abstinent or use at least two
   forms of effective contraceptive with a failure rate of < 1% per year during the
   treatment period and for at least 3 months after the last dose of cobimetinib and at
   least 5 months after the last dose of atezolizumab or pembrolizumab

   - For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
   contraceptive measures (e.g. condom), and agreement to refrain from donating sperm,
   for at least 3 months after the last dose of cobimetinib

   - Willingness and ability of patients to report selected study outcomes (e.g., GHS and
   HRQoL) using an electronic device or paper backup questionnaires.

Exclusion Criteria:

General Exclusion Criteria

   - Inability to swallow medications

   - Malabsorption condition that would alter the absorption of orally administered
   medications

   - Pregnancy, breastfeeding, or intention of becoming pregnant during the study

   - History of severe hypersensitivity reactions to components of the cobimetinib,
   atezolizumab, or pembrolizumab formulations

   - Current or recent treatment with therapeutic antibiotics, live attenuated vaccines or
   systemic immunostimulatory/immunosuppresive medication

   - Any serious medical condition or abnormality in clinical laboratory tests that, in the
   investigator's judgment, precludes the patient's safe participation in and completion
   of the study Cancer-Related Exclusion Criteria

   - Ocular melanoma

   - Major surgery or radiotherapy within 21 days prior to Day 1 of Cycle 1 or anticipation
   of needing such procedure while receiving study treatment

   - Uncontrolled tumor-related pain

   - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated
   drainage more than once every 28 days

   - Active or untreated central nervous system (CNS) metastases Exclusions Related to
   Cardiovascular Disease

   - Unstable angina, new-onset angina within last 3 months, myocardial infarction within
   the last 6 months prior to Day 1 of Cycle 1, or current congestive heart failure
   classified as New York Heart Association Class II or higher

   - Left ventricular ejection fraction (LVEF) below institutional lower limit of normal or
   <50%, whichever is lower

   - Poorly controlled hypertension, defined as sustained, uncontrolled, non-episodic
   baseline hypertension consistently above 159/99 mmHg despite optimal medical
   management

   - History or presence of an abnormal electrocardiogram (ECG) that is clinically
   significant in the investigator's opinion, including complete left bundle branch
   block, second- or third degree heart block, or evidence of prior myocardial infarction
   Exclusions Related to Infections

   - HIV infection

   - Active tuberculosis infection

   - Severe infections within 4 weeks prior to Day 1 of Cycle 1, including, but not limited
   to, hospitalization for complications of infection, bacteremia, or severe pneumonia

   - Signs or symptoms of clinically relevant infection within 2 weeks prior to Day 1 of
   Cycle 1

   - Treatment with oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1

   - Active or chronic viral hepatitis B or C infection Exclusions Related to Ocular
   Disease

   - Known risk factors for ocular toxicity Exclusions Related to Autoimmune Conditions and
   Immunomodulatory Drugs

   - Active or history of autoimmune disease or immune deficiency

   - Prior allogeneic stem cell or solid organ transplantation

   - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced or
   idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan

   - Treatment with systemic immunosuppressive medications within 2 weeks prior to Day 1,
   Cycle 1 Exclusions Related to Other Medical Conditions or Medications

   - Active malignancy (other than melanoma) or a prior malignancy within the past 3 years

   - Any Grade >=3 hemorrhage or bleeding event within 28 days of Day 1 of Cycle 1

   - History of stroke, reversible ischemic neurological defect, or transient ischemic
   attack within 6 months prior to Day 1

   - Proteinuria >3.5 gm/24 hr

   - Consumption of foods, supplements, or drugs that are strong or moderate CYP3A4 enzyme
   inducers or inhibitors at least 7 days prior to Day 1 of Cycle 1 and during study
   treatment

Intervention(s):

drug: Cobimetinib

drug: Atezolizumab

drug: Pembrolizumab

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
ccto
650-498-7061

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