This study will evaluate the preliminary efficacy, safety, and pharmacokinetics of
cobimetinib and atezolizumab in participants with advanced BRAF V600-WT, metastatic, or
unresectable locally advanced melanoma who have progressed on prior anti−PD-1 therapy.
Inclusion criteria
- Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc BRAF V600
WT (locally advanced) melanoma
- Documentation of BRAF V600 mutation-negative status in melanoma tumor tissue
(archival or newly obtained) through use of a clinical mutation test approved by the
local health authority
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1
- Disease progression on or after treatment with a programmed death (PD)-1 inhibitor
either as monotherapy or in combination with other agent(s)
Additional Disease-Specific Inclusion Criteria in Cohort B (Biopsy Cohort)
- Progressed on or after anti-PD-1 therapy within 12 weeks before study start
- Received a minimum of two cycles of anti-PD-1 therapy
- Meet the following criteria for resistance to an anti-PD-1 agent: primary resistance
defined as disease progression, according to RECIST v1.1, as best response; secondary
resistance defined as disease progression after initial confirmed response according
to RECIST v1.1
- Consent to undergo tumor biopsies of accessible lesions, before and during treatment
and at radiographic progression, for biomarker analyses.
- Have at least two accessible lesions that are amenable to excisional, punch, or
core-needle (minimum three cores and minimum diameter 18 gauge; however, 16 gauge is
desirable) biopsy without unacceptable risk of a major procedural complication.
- Ability to comply with the study protocol, in the investigator's judgment
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Available and adequate baseline tumor tissue sample
- Life expectancy ≥ 18 weeks
- Adequate hematologic and end-organ function, defined by laboratory test results,
obtained within 14 days before initiation of study treatment
- For women of childbearing potential: abstinent or use an effective form of
contraceptive method for at least 3 months for cobimetinib and at least 5 months for
atezolizumab
- For men: abstinent or use contraceptive measures and agreement to refrain from
donating sperm for at least 3 months after cobimetinib and atezolizumab
Exclusion criteria
- Prior treatment with a mitogen activated-protein kinase (MAPK) inhibitor
- Major surgical procedure other than for diagnosis within 4 weeks before initiation of
study treatment, or anticipation of need for a major surgical procedure during the
course of the study
- Traumatic injury within 2 weeks before initiation of study treatment
- Palliative radiotherapy within 14 days before initiation of study treatment
- Active malignancy (other than BRAF V600 mutation-negative melanoma) or malignancy
within 3 years
- Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1
except for alopecia
- History or evidence of ongoing serous retinopathy or retinal vein occlusion (RVO) at
baseline
- History of clinically significant cardiac dysfunction
- Active or untreated central nervous system (CNS) metastases
- History of metastases to brain stem, midbrain, pons, or medulla, or within 10 mm of
the optic apparatus (optic nerves and chiasm)
- Ocular melanoma
- History of leptomeningeal metastatic disease
- History of intracranial hemorrhage
- Current severe, uncontrolled systemic disease other than cancer
- Anticipated use of any concomitant medication during or within 7 days before
initiation of study treatment that is known to cause QT prolongation
- Any psychological, familial, sociological, or geographic condition that may hamper
compliance with the protocol and follow-up after treatment discontinuation
- History of malabsorption or other clinically significant metabolic dysfunction that
may interfere with absorption of oral study treatment
- 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 (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest CT scan
- History of autoimmune disease with exceptions listed in more detail in the protocol
- History of organ transplantation including allogeneic bone marrow transplantation
- Known clinically significant liver disease
- Active tuberculosis
- Human immunodeficiency virus (HIV) infection
- Active or chronic hepatitis B or C infection
- Severe infection within 4 weeks before initiation of study treatment
- Signs or symptoms of infection within 2 weeks before initiation of study treatment
- Treatment with oral or intravenous (IV) antibiotics within 2 weeks prior to Day 1 of
Cycle 1
- Treatment with systemic immunosuppressive medications within 2 weeks prior to Day 1
Cycle 1
- Treatment with a live, attenuated vaccine within 4 weeks before initiation of study
treatment, or anticipation of need for such a vaccine during the course of the study
- Known hypersensitivity to any component of the atezolizumab or cobimetinib
formulations
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins
- Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that contraindicates the use of an investigational drug, may
affect the interpretation of the results, or may render the participant at high risk
for treatment complications
- Treatment with any other investigational agent or participation in another clinical
study with therapeutic intent
- Inability or unwillingness to swallow pills
- Requirement for concomitant therapy or food that is prohibited during the study
