A Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Participants With Solid Tumors
Condition: Solid Tumors
MeSH terms: Neoplasms
Intervention: Cobimetinib; Atezolizumab; Atezolizumab Cohort 7
Intervention description: Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.; Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.; Only for participants in cohort 7, the first dose of atezolizumab of 840 mg will be given by IV infusion on Day 15 of Cycle 1; thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles.
Intervention MeSH terms: Atezolizumab; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 87.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a study to evaluate the efficacy, safety, and pharmacokinetics of cobimetinib plus
      atezolizumab in participants with advanced solid tumors including the following cohorts:
      squamous cell carcinoma of the head and neck (SCCHN), urothelial carcinoma (UC), and renal
      cell carcinoma (RCC).
    

Eligibility criteria:

        Inclusion Criteria:

        General Inclusion Criteria:

          -  Age ≥18 years

          -  Ability to comply with the study protocol, in the investigator's judgment

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

          -  Life expectancy ≥3 months, as determined by the investigator

          -  Adequate hematologic and end-organ function

        Cancer-Related Inclusion Criteria:

          -  Patients must have measurable disease by computed tomography (CT) or magnetic
             resonance imaging (MRI) scan per RECIST v1.1.

          -  Availability to provide a representative tumor specimen biopsy

          -  Evidence of tumor progression on or after the last treatment regimen received and
             within 6 months prior to study enrollment

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use a non-hormonal contraceptive method with a failure
             rate of <1% per year during the treatment period and for at least 5 months after the
             last dose of atezolizumab and within 3 months after the last dose of cobimetinib

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             contraceptive measures, and agreement to refrain from donating sperm during the
             treatment period and for at least 3 months after the last dose of cobimetinib

        Exclusion Criteria:

        General Exclusion Criteria:

          -  Inability to swallow medications

          -  Malabsorption condition that would alter the absorption of orally administered
             medications

          -  Poor peripheral venous access

          -  Prior treatment with cobimetinib or a MEK inhibitor

          -  Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies,
             including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies

          -  Treatment with investigational therapy within 14 days prior to initiation of study
             treatment

          -  Any anti-cancer therapy, including chemotherapy or hormonal therapy, within 2 weeks
             prior to initiation of study treatment

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins

          -  Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary
             cells or any component of the atezolizumab formulation, or any component of the
             cobimetinib formulation

          -  History of serous retinopathy, retinal vein occlusion (RVO), or evidence of ongoing
             serous retinopathy or RVO at baseline

          -  Major surgical procedure other than for diagnosis within 4 weeks prior to initiation
             of study treatment, or anticipation of need for a major surgical procedure during the
             study

          -  Uncontrolled tumor-related pain

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated
             drainage more than once every 28 days

          -  Uncontrolled hypercalcemia (ionized calcium >1.5 millimoles per liter [mmol/L],
             calcium >12 milligrams per deciliter [mg/dL], or corrected calcium greater than the
             upper limit of normal [ULN]) or symptomatic hypercalcemia requiring continued use of
             bisphosphonate therapy

          -  Active or untreated central nervous system (CNS) metastases

          -  Pregnancy or breastfeeding, or intending to become pregnant during the study

        Exclusion Criteria based on Organ Function or Medical History

        Cardiovascular

        Patients who meet the following cardiovascular exclusion criterion will be excluded from
        study entry:

          -  Left ventricular ejection fraction (LVEF) below the institutional lower limit of
             normal or <50%, whichever is lower

        Infections Patients who meet any of the following infection exclusion criteria will be
        excluded from study entry:

          -  Positive human immunodeficiency virus (HIV) test at screening

          -  Active hepatitis B virus (HBV) infection (chronic or acute)

          -  Active hepatitis C virus (HCV) infection

          -  Active tuberculosis

          -  Severe infection within 4 weeks prior to initiation of study treatment, including, but
             not limited to, hospitalization for complications of infection, bacteremia, or severe
             pneumonia

          -  Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
             of study treatment