Inclusion Criteria:
- Signed informed consent form
- Ability to comply with the study protocol, in the investigator's judgment
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
version (v) 1.1; previously irradiated lesions can be considered as measurable disease
only if progressive disease has been unequivocally documented at that site since
radiation; the pleural mesothelioma cohort will require measurable disease according
to modified RECIST
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L without granulocyte colony-stimulating
factor support, obtained within 14 days prior to initiation of study treatment
- Lymphocyte count >= 0.5 x 10^9/L, obtained within 14 days prior to initiation of study
treatment
- Platelet count >= 100 x 10^9/L without transfusion, obtained within 14 days prior to
initiation of study treatment
- White blood cell (WBC) count >= 2500/ul, obtained within 14 days prior to initiation
of study treatment
- Hemoglobin >= 90 g/L (patients may be transfused to meet this criterion), obtained
within 14 days prior to initiation of study treatment
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline
phosphatase (ALP) =< 2.5 x upper limit of normal (ULN), obtained within 14 days prior
to initiation of study treatment, with the following exceptions: patients with
documented liver metastases: AST and ALT =< 5 x ULN; patients with documented liver or
bone metastases: alkaline phosphatase (ALP) =< 5 x ULN
- Serum bilirubin 1.5 x ULN, obtained within 14 days prior to initiation of study
treatment
- Serum creatinine =< 1.5 x ULN, obtained within 14 days prior to initiation of study
treatment
- Serum albumin >= 2.5 g/dL, obtained within 14 days prior to initiation of study
treatment
- For patients not receiving therapeutic anticoagulation: international normalized ratio
(INR) or activated partial thromboplastin time (aPTT) =< 1.5 x ULN, obtained within 14
days prior to initiation of study treatment
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use a contraceptive method with a failure rate of < 1%
per year during the treatment period and for 6 months after the last dose of study
treatment
- A woman is considered to be of childbearing potential if she is postmenarchal, has not
reached a postmenopausal state (>= 12 continuous months of amenorrhea with no
identified cause other than menopause), and has not undergone surgical sterilization
(removal of ovaries and/or uterus); examples of contraceptive methods with a failure
rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and
copper intrauterine devices; the reliability of sexual abstinence should be evaluated
in relation to the duration of the clinical trial and the preferred and usual
lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation,
symptothermal, or postovulation methods) and withdrawal are not acceptable methods of
contraception
- Appendiceal adenocarcinoma basket
- Metastatic appendiceal adenocarcinoma
- Not considered candidate for curative surgery
- Nasopharyngeal carcinoma basket
- Metastatic or locally recurrent disease not amenable to curative intent treatment
- Any number of prior therapies, including 0
- Human papilloma virus-associated cancers
- Histologically proven squamous carcinoma of the anal canal, penile, vaginal,
vulva, or refractory cervical cancer with progression or intolerance to at least
one treatment regimen including cisplatin, oxaliplatin or carboplatin will be
enrolled; human papilloma virus (HPV) confirmation is not required
- Patients must have metastatic disease not amenable to surgical resection
- If human immunodeficiency virus (HIV)+ positive, all patients infected with human
immunodeficiency virus (HIV) and CD4+ T cell count > 400 cells/mm^3 may be
eligible for study
- Patients co-infected with hepatitis B virus and/or hepatitis C virus may be
included in this study provided that their liver function tests remain within the
limits listed above; patients must be followed by a hepatologist during the
course of this study
- Merkel cell carcinoma basket
- Metastatic or locally recurrent disease not amenable to curative intent treatment
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies,
including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Any number of prior therapies
- Neuroendocrine tumors, pancreatic basket
- Grade 1 or grade 2 (or described as low grade, intermediate grade, well
differentiated, or moderately differentiated) according to reviewing pathologist
- Progressive disease over the preceding 12 months
- Any number of prior therapies, including 0
- Patients using a somatostatin analogue for symptom control must be on stable
doses for 56 days prior to enrollment
- Neuroendocrine tumors, extrapancreatic basket
- Grade 1 or grade 2 (or described as low grade, intermediate grade, well
differentiated, or moderately differentiated; typical or atypical carcinoid if
originating in lung) according to reviewing pathologist
- Progressive disease over the preceding 12 months
- Any number of prior therapies, including 0
- Patients using a somatostatin analogue for symptom control must be on stable
doses for 56 days prior to enrollment
- Peritoneal mesothelioma basket
- Refractory or intolerant to platinum and pemetrexed systemic therapy
- Any number of prior therapies
- Pleural mesothelioma basket
- Metastatic or locally recurrent disease not amenable to curative intent treatment
- Refractory to platinum and pemetrexed systemic therapy
- Any number of prior therapies
Exclusion Criteria:
- Treatment for the studied cancer within 28 days prior to initiation of study treatment
- Treatment with investigational therapy within 28 days 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
- Known allergy or hypersensitivity to any component of the atezolizumab formulation
- Known allergy or hypersensitivity to any component of the bevacizumab 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, antiphospholipid
antibody syndrome, Wegener granulomatosis, Sjogren's syndrome, Guillain-Barre
syndrome, or multiple sclerosis, with the following exceptions: patients with a
history of autoimmune-related hypothyroidism who are on thyroid replacement hormone
are eligible for the study; patients with controlled type 1 diabetes mellitus who are
on an insulin regimen are eligible for the study; patients with eczema, psoriasis,
lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g.,
patients with psoriatic arthritis are excluded) are eligible for the study provided
all of following conditions are met:
- Rash must cover < 10% of body surface area
- Disease is well controlled at baseline and requires only low-potency topical
corticosteroids
- No occurrence of acute exacerbations of the underlying condition requiring
psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents,
oral calcineurin inhibitors, or high potency or oral corticosteroids within the
previous 12 months
- 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 computed tomography (CT) scan; (history of
radiation pneumonitis in the radiation field [fibrosis] is permitted)
- Positive HIV test at screening (except in cohort 3, HPV-associated cancers)
- Except in cohort 3, HPV-associated cancers, active hepatitis B virus (HBV) infection
(chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg)
test at screening; patients with a past or resolved HBV infection, defined as having a
negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test and
negative HBV deoxyribonucleic acid (DNA) test at screening, are eligible for the study
- Except in cohort 3, HPV-associated cancers active hepatitis C virus (HCV) infection,
defined as having a positive HCV antibody test followed by a positive HCV RNA test at
screening; the HCV RNA test will be performed only for patients who have a positive
HCV antibody test
- 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; patients receiving prophylactic antibiotics (e.g., to prevent a
urinary tract infection or chronic obstructive pulmonary disease exacerbation) are
eligible for the study
- Significant cardiovascular disease, such as New York Heart Association cardiac disease
(class II or greater), myocardial infarction, or cerebrovascular accident within 3
months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
- 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
course of the study
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study
treatment, or anticipation of need for such a vaccine during the course of the study,
or up to 5 months following the anticipated last dose of atezolizumab
- Malignancies other than the disease under study within 5 years prior to cycle 1, day
1, with the exception of those with a negligible risk of metastasis or death and with
expected curative outcome (such as adequately treated carcinoma in situ of the cervix,
basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically
with curative intent) or undergoing active surveillance per standard-of-care
management (e.g., chronic lymphocytic leukemia Rai stage 0)
- 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
- Except for cohort 4, Merkel cell carcinoma, prior treatment with CD137 agonists or
immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1
therapeutic antibodies
- Treatment with systemic immunostimulatory agents (including, but not limited to,
interferon and interleukin 2 [IL-2]) within 4 weeks or five half-lives of the drug
(whichever is longer) prior to initiation of study treatment
- Treatment with systemic immunosuppressive medication (including, but not limited to,
corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-TNF-· agents) within 2 weeks prior to initiation of study treatment, or
anticipation of need for systemic immunosuppressive medication during the course of
the study, with the following exceptions: patients who received low-dose
immunosuppressant medication are eligible for the study; patients who received
mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive
pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic
hypotension or adrenal insufficiency are eligible for the study
- Pregnant or breastfeeding, or intending to become pregnant during the study; women of
childbearing potential must have a negative serum pregnancy test result within 14 days
prior to initiation of study treatment
- Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg
and/or diastolic blood pressure > 100 mmHg); anti-hypertensive therapy to maintain a
systolic blood pressure < 150 mmHg and/or diastolic blood pressure < 100 mmHg is
permitted
- Prior history of hypertensive crisis or hypertensive encephalopathy
- History of stroke or transient ischemic attack within 6 months prior to cycle 1, day 1
- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
recent peripheral arterial thrombosis) within 6 months prior to cycle 1, day 1
- Patients with a baseline electrocardiography (ECG) demonstrating a corrected QT (QTc)
> 460 ms
- Evidence of bleeding diathesis or clinically significant coagulopathy (in the absence
of therapeutic anticoagulation)
- Current or recent (within 10 calendar days prior to cycle 1, day 1) use of
dipyramidole, ticlopidine, clopidogrel, or cilostazol
- Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device, within 7 calendar days prior to the first dose of bevacizumab
- History of abdominal or tracheoesophageal fistula or gastrointestinal perforation
within 6 months prior to cycle 1, day 1
- Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine
parenteral hydration, parenteral nutrition, or tube feeding
- Evidence of abdominal free air not explained by paracentesis or recent surgical
procedure
- Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
- Proteinuria, as demonstrated by urine dipstick or > 1.0 g of protein in a 24-hour
urine collection; all patients with >= 2+ protein on dipstick urinalysis at baseline
must undergo a 24-hour urine collection for protein
- Appendiceal adenocarcinoma basket
- Complete or partial bowel obstruction
- Epstein-Barr virus-associated nasopharyngeal carcinoma basket:
- None
- Human papilloma virus-associated cancers basket
- None
- Merkel cell carcinoma basket:
- None
- Neuroendocrine tumors, pancreatic basket:
- Grade 3, poorly differentiated neuroendocrine carcinoma
- Large cell or small cell histology
- Neuroendocrine tumors, extrapancreatic basket:
- Grade 3, poorly differentiated neuroendocrine carcinoma
- Large cell or small cell histology
- Peritoneal mesothelioma basket:
- None
- Pleural mesothelioma basket:
- None
