BEACON - ABC in Recurrent Platinum Resistant HGSOC

Exclusion Criteria

• •Prior treatment with CD137 agonists or immune checkpoint blockage therapies, anti programmed death-1, anti-program death-ligand 1, MEK inhibitor. Prior treatment with bevacizumab is allowed, provided a \>6 month treatment free interval from the last previous dose of bevacizumab to registration.
• •Treatment with systemic immunosuppressive medications, including but not limited to corticosteroids, cyclophosphamide, azathioprine, cyclosporine, methotrexate, thalidomide and anti-tumour necrosis factor (TNF) agents within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial
• •Patient has had surgical procedures or significant traumatic injury within 60 days prior to registration, or it is anticipated that they will require major surgical procedures during the course of the study.
• •Patients at high risk of bowel perforation or fistula
• •History of bowel obstruction, including sub- occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess.
• •History of colonic anastamosis
• •Clinical symptoms of recent bowel obstruction or paralytic ileus, but excluding postoperative, or evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan.
• •Prior treatment with Hyperthermic intraperitoneal chemotherapy (HIPEC)
• •Prior whole abdominal or pelvic radiotherapy
• •Untreated CNS metastases. Treatment of brain metastases, either by surgical or radiation techniques, must have been completed at least 4 weeks prior to registration. Prior to registration, there are no signs of progression or hemorrhage of treated CNS metastases, eg. by MRI Brain. No ongoing need for corticosteroid treatment (anticonvulsants are allowed)
• •Treatment with any investigational agent or approved therapy within 28 days or two investigational agent half-lives (whichever is longer) prior to registration.
• •Malignancies other than ovarian cancer within 5 years prior to registration (or within 3 years prior to registration, provided probability of recurrence is \<10%) with the exception of adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, melanoma in situ, and ductal carcinoma in situ treated surgically with curative intent.
• •Prior radiation therapy within 28 days prior to registration and/or persistence of radiation-related adverse effects.
• •Spinal cord compression not definitively treated with surgery and/or radiation.
• •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
• •History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
• •Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to registration or at any time during the study and for at least 5 months after the last dose of study drug.
• •Active infection requiring IV antibiotics at screening
• •Patients with known HIV infection or a history of positive tests for HIV/AIDS
• •Current or recent (within 10 days of registration) use of acetylsalicylic acid (\> 325 mg/day), clopidogrel (\>75 mg/day) or thrombolytic agents for therapeutic purposes
• •Patient has taken the following foods/supplements within 7 days prior to registration: St John's wort or hyperforin (potent CYP3A4 enzyme inducer) or Grapefruit juice (potent CYP3A4 enzyme inhibitor)
• •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• •Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any components of cobimetinib, atezolizumab, or bevacizumab formulations
• •History of clinically significant cardiac or pulmonary dysfunction including the following; Inadequately controlled hypertension (that is defined as systolic blood pressure \> 140 mmHg and/or diastolic blood pressure \> 90 mmHg that is treated or untreated) or History of myocardial infarction within 6 months prior to first dose of study drug in Cycle 1
• •Prior history of hypertensive crisis or hypertensive encephalopathy
• •Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of registration
• •History of stroke or transient ischemic attack within 6 months prior of registration
• •Patient has has a serious non-healing wound, active ulcer or untreated bone fracture
• •History of hemoptysis (\>½ teaspoon of bright red blood per episode), or any other serious haemorrhage or at risk of bleeding (gastrointestinal history of bleeds, gastrointestinal ulcers, etc.)
• •History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding
• •Any previous venous thromboembolism ≥ Grade 3
• •Left ventricular ejection fraction below institutional lower limit of normal
• •Uncontrolled serious medical or psychiatric illness
• •Uncontrolled tumour pain
• •History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• •History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion or neovascular macular degeneration.