A Clinical Study of Cobimetinib Administered in Combination With Niraparib, With or Without Atezolizumab to Patients With Advanced Platinum-sensitive Ovarian Cancer

Inclusion Criteria

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

- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures, including the completion of patient-reported
outcome questionnaires

- Histological diagnosis of high-grade serous or Grade 2 or Grade 3 endometrioid
epithelial ovarian, fallopian tube, or primary peritoneal cancer

- Previous treatment with a minimum of one and a maximum of two prior platinum based
treatment regimens

- Platinum-sensitive disease

- Availability of tumor biopsy tissue prior to first dose of study treatment with
confirmation by the central laboratory that the sample is not only of adequate quality
but also assignable to a molecularly defined subgroup based on breast cancer
susceptibility gene (BRCA) and loss of heterozygosity (LOH) status

- Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors,
version 1.1 (RECIST v1.1)

- Adequate hematologic and organ function

- Eastern Cooperative Oncology Group Performance Status of 0 or 1

- Life expectancy of at least 12 weeks

- Resolved or stabilized toxicities resulting from previous therapy to Grade 1

- Negative HIV test at screening

- Negative hepatitis B surface antigen and total hepatitis B core antibody (HBcAb) test,
or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA <
500 IU/mL test at screening

- Negative hepatitis C virus (HCV) antibody test, or positive HCV antibody test followed
by a negative HCV RNA test at screening

- For women of childbearing potential: Women must remain abstinent or use two
contraceptive methods with a failure rate of <1% per year during the treatment period
and for at least 3 months after the last dose of cobimetinib, 6 months after the last
dose of niraparib, and 5 months after the last dose of atezolizumab. Women must
refrain from donating eggs during this same period

Exclusion Criteria

- Prior treatment with mitogen-activated protein kinase inhibitor, polyadenosine
diphosphate-ribose polymerase inhibitor, or immune checkpoint inhibitor therapies

- Prior chemotherapy, hormonal therapy, radiotherapy, antibody therapy, or other
immunotherapy, gene therapy, vaccine therapy, or treatment with experimental drugs
within 14 days prior to first dose of study treatment

- Treatment with systemic immunostimulatory agents within 28 days or 5 half-lives of the
drug prior to initiation of study treatment

- Treatment with systemic immunosuppressive medication 14 days prior to initiation of
study treatment, or anticipation of need for systemic immunosuppressive medication
during the study

- History of other malignancy that could affect compliance with the protocol or
interpretation of results, or known to have potentially fatal outcome

- Symptomatic and/or untreated central nervous system metastases

- Surgical procedure, significant traumatic injury within 14 days prior to enrollment,
or anticipation of need for major surgical procedure during the study

- Minor surgical procedure within 3 days

- History or evidence of retinal pathology on ophthalmic examination

- Left ventricular ejection fraction below institutional lower limit of normal

- History of clinically significant cardiovascular dysfunction

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

- History or evidence of inherited bleeding diathesis or significant coagulopathy at
risk for bleeding

- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins, or to any component of the
atezolizumab formulation

- Known allergy or hypersensitivity to any component of the cobimetinib or niraparib
formulation

- Active or history of autoimmune disease or immune deficiency including, but not
limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid
antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barre syndrome,
or multiple sclerosis

- Uncontrolled serious medical or psychiatric illness

- History of malabsorption or other condition that would interfere with absorption of
oral study drugs, including preexisting duodenal stent or ongoing intestinal
obstruction

- Active tuberculosis

- Severe infection within 14 days 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 7 days prior to initiation of
study treatment

- Treatment with a live, attenuated influenza vaccine within 28 days prior to study
treatment initiation, at any time during the study, and for at least 5 months after
the last dose of study drug

- 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 patient at high risk from
treatment complications

- Previous treatment with strong CYP3A inhibitors (such as ketoconazole and
clarithromycin), strong CYP3A inducers (such as carbamazepine and phenytoin), and
moderate CYP3A inducers (such as efavirenz, modafinil) within 7 days prior to the
initiation of study treatment or with ongoing requirements for these medications

- Pregnancy or breastfeeding, or intention to become pregnant during the study