Solid Tumors

This study will evaluate the safety, efficacy, and pharmacokinetics of atezolizumab in combination with bevacizumab, bevacizumab + oxaliplatin, leucovorin and 5-fluorouracil (5-FU) (FOLFOX), vanucizumab, nab-paclitaxel + gemcitabine, FOLFOX, or 5-FU + cisplatin, in participants with solid tumors.

TECENTRIQ

Atezolizumab (RO5541267)

Injection

1200 mg/20 ml

Safety Outcome Measures
The safety, tolerability, and preliminary efficacy of atezolizumab administered in combination
with bevacizumab, bevacizumab FOLFOX, vanucizumab, nab-paclitaxel  gemcitabine,
FOLFOX, or 5-FU  cisplatin, will be assessed using the following primary safety outcome
measures:
x Incidence, nature, and severity of adverse events and laboratory abnormalities graded per
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Version 4.0
Additional safety outcome measures will include the number of cycles and the dose intensity of
each component of the treatment regimen, as well as changes in vital signs, ECGs, and clinical
laboratory test results during and after atezolizumab administration in combination with
bevacizumab and/or chemotherapy. Incidence of ATAs to atezolizumab, bevacizumab, and
vanucizumab will also be measured.

Pharmacokinetic Outcome Measures
Sparse PK samples will be collected for all five treatment arms.
x Atezolizumab concentration at predose and 30 minutes after the end of the infusion (all
arms)
x Bevacizumab concentration at predose and 30 minutes after the end of the infusion (Arm A,
Arm B, and Group D2)
x Vanucizumab concentrations at predose and 30 minutes after the end of the infusion
(Group D1)
x Oxaliplatin concentration at predose and 510 minutes before the end of the infusion
(Arm B and Group E1)
x 5-FU concentration at predose, immediately following bolus administration and 2 hours
post-bolus dose (Arms B and E)
x Cisplatin (total) concentration at predose and 510 minutes before the end of the infusion
(Group E2)
x nab-Paclitaxel concentration at predose, 510 minutes before the end of the infusion, and
1 hour after the end of the infusion (Arm C)
x Gemcitabine concentration at predose, 510 minutes before the end of the infusion, and
1 hour after the end of the infusion (Arm C)

Activity Outcome Measures
The following activity outcome measures will be assessed:
x Best overall response
x Objective response, defined as a complete or partial response
x Duration of response (DOR), defined as the first occurrence of a documented objective
response until the time of disease progression based on investigator assessment or death
from any cause, whichever occurs first
x Progression-free survival (PFS), defined as the time from the first study treatment to the
first occurrence of disease progression based on investigator assessment or death from
any cause, whichever occurs first
x Overall survival (OS), defined as the time from the date of first study treatment to the date
of death from any cause
x Arm A and Arm D only
Time to radiological progression, defined as the time from the first study treatment to
the first occurrence of disease progression based on investigators radiologic
assessment
x Arm D only
Time to symptomatic progression, as defined by the Assessment of FACT
Hepatobiliary Symptom Index 8 (FHSI-8) questionnaire
All activity outcome measures will be determined by use of Response Evaluation Criteria in
Solid Tumors (RECIST) Version 1.1 and immune-modified RECIST. For Arm D, HCC-specific
modified RECIST will also be used in addition to RECIST v1.1 and immune-modified RECIST.

General Inclusion Criteria
Patients must meet the following criteria for study entry:
x Signed Informed Consent Form
x Women or men aged t 18 years
x Able to comply with the study protocol, in the investigator’s judgment
x Availability at the site of tumor specimens in paraffin blocks (preferred) or t 16 unstained
slides, with an associated pathology report, prior to study entry
If archival tissue is either insufficient or unavailable, the patient may still be eligible,
upon discussion with the Medical Monitor, if the patient:
Willing to provide t 16 unstained, serial slides
or
Is willing to consent to and undergo a pre-treatment core or excisional biopsy of
the tumor (cytologic or fine-needle aspiration samples are not acceptable)
Tumor tissue from bone metastases is not evaluable for tumor PD-L1 expression and is
therefore not acceptable. For core needle biopsy specimens, at least three cores
should be submitted for evaluation.
For patients with HCC in Arm A and Arm D, a core needle biopsy specimen is required
during the screening period only if archival tissue is not available or was
collected !6 months prior to treatment Cycle 1, Day 1. Trans-jugular biopsy tissue
sample collection from patients with HCC who are at high risk of bleeding may be
allowed. Archival tumor tissue could be submitted prior to the submission of fresh
tumor tissue.
x Measurable disease per RECIST v1.1
x Eastern Cooperative Oncology Group performance status of 0 or 1
x Adequate hematologic and end organ function, defined by the following laboratory results
obtained within 2 weeks prior to initiation of study treatment (Cycle 1, Day 1):
ANC t1500/PL (without granulocyte colony-stimulating factor support within 2 weeks
prior to Cycle 1, Day 1)
WBC counts t 2,500/PL
Lymphocyte count t 500/PL (or within local laboratory normal limits)
Platelet count t 100,000/PL
Hemoglobin t 9.0 g/dL
Serum bilirubin d 1.5 u upper limit of normal (ULN) with the following exception:
Patients with known Gilbert disease who have serum bilirubin level d3 u ULN
may be enrolled.
x AST and ALT d 2.5 ULN with the following exception:
Patients with documented liver metastases: AST and/or ALT d 5 u ULN
Patients with documented liver or bone metastases: alkaline phosphatase d 5 u ULN
x Alkaline phosphatase d 2.5 u ULN with the following exception:
Patients with documented liver or bone metastases: alkaline phosphatase d 5 u ULN
x Serum creatinine d 1.5 u ULN or creatinine clearance t 50 mL/min
x INR and aPTT d 1.5 u ULN within 2 weeks prior to enrollment
This applies only to patients who are not receiving therapeutic anticoagulation; patients
receiving therapeutic anticoagulation should be on a stable dose.
x Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to
Grade d 1 prior to study entry, with the exception of alopecia
x For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use an effective form of contraceptive methods that result in a
failure rate of  1% per year (e.g., surgical sterilization, a reliable barrier method, birth
control pills, or contraceptive hormone implants) during the treatment period and for
at least 28 days after the last dose of capecitabine (Arm B only, if applicable), 4 months
after the last dose of oxaliplatin, 5 months after the last dose of atezolizumab, or 6 months
after the last dose of bevacizumab, vanucizumab, 5-FU, cisplatin, gemcitabine, or
nab-paclitaxel.
A woman is considered to be of childbearing potential if she is postmenarcheal, has not
reached a postmenopausal state (t12 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, established, proper use of hormonal contraceptives that
inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and IUDs.
The reliability of sexual abstinence should be evaluated in relation to the duration of the
clinical study 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.
x For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures, and agreement to refrain from donating sperm, as defined below:
With female partners of childbearing potential, men must remain abstinent or use a
condom plus an additional contraceptive method that together result in a failure rate
of  1% per year during the treatment period, at least 3 months after the last dose of
capecitabine (Arm B only, if applicable), 4 months after the last dose of oxaliplatin, and
6 months after the last dose of bevacizumab, vanucizumab, 5-FU, cisplatin,
gemcitabine, and/or nab-paclitaxel. Men must refrain from donating sperm during this
same period.
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.
x Women who are not postmenopausal (t 12 months of nontherapy induced amenorrhea) or
surgically sterile must have a negative serum pregnancy test result within 14 days prior to
initiation of study drug.
Arm-Specific Inclusion Criteria
Hepatocellular Carcinoma Cancer (Arm A and Arm D)
x Patients with advanced or metastatic and/or unresectable HCC with diagnosis confirmed by
histology/ cytology or clinically by American Association for the Study of Liver Diseases
criteria in cirrhotic subjects. Patients without cirrhosis require histological confirmation of
diagnosis.
x The patient has disease that is not amenable to a curative treatment approach
(i.e., resection, transplantation)
x No prior line of systemic therapy
Includes patients who are sorafenib-naive
x Willing to undergo biopsy if archival tissue is not available or if archival tissue was taken
! 6 months from Cycle 1, Day 1
x Child-Pugh score of up to B7
x Serum bilirubin d 3uULN
x INR and aPTT d 2uULN
x Albumin ! 2.8 g/dL
x Documented virology status of hepatitis, as confirmed by screening hepatitis B surface
antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and/or antihepatitis C
virus (HCV)
x Anti-viral therapy per local standard-of-care if active hepatitis B virus (HBV) or HCV
infection
For patients with HBV infection:
HBV DNA 500 IU/mL for at least the preceding 3 months
Willing to take anti-HBV treatment (e.g., entecavir) for the length of the study
Ongoing anti-HBV treatment (e.g., entecavir) at study entry and for a minimum of
3 months prior to study entry
Gastric Cancer (Arm B)
x Histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma of
the stomach or GEJ in patients who have not received prior systemic therapy for metastatic
disease
Patients who have received chemotherapy in the adjuvant setting are allowed, provided
at least 6 months have elapsed since completion of the last dose, and any related
toxicities have been reduced to dGrade 1.
x Absence of human epidermal growth factor 2 (HER2) expression documented as in situ
hybridization (ISH)negative on previously collected and assessed tumor tissue upon initial
diagnosis of disease. HER2 negativity will be retrospectively confirmed by central
laboratory testing after enrollment.
HER2-negative status will be determined on the basis of archival or, if not available,
pre-screening biopsy material and defined as an ISH non-amplified (ratio of HER2 to
CEP17  2.0 or single probe average HER2 gene copy number  4 signals/cell)
or
IHC 0 or IHC 1
(if more than one test result is available and not all results meet the
inclusion criterion definition, all results should be discussed with the Medical Monitor to
establish eligibility of the patient)
Metastatic Pancreatic Cancer (Arm C)
x Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas
Definitive diagnosis of metastatic pancreatic adenocarcinoma will be made by
integrating the histopathological data within the context of clinical and radiographic data.
Participants with islet cell neoplasms will be excluded.
x No previous radiotherapy, surgery, chemotherapy, or investigational therapy for the
treatment of metastatic disease
Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer in the adjuvant
setting is allowed, provided at least 6 months have elapsed since completion of the last dose
and any related toxicities have been reduced to d Grade 1. Patients who have received
cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting are not
eligible for this study.
Metastatic Esophageal Cancer (Arm E)
x Histologically or cytologically confirmed locally mEC or metastatic adenocarcinoma of the
GEJ Siewert Classification Type I in patients who have not received prior systemic therapy
for primary and metastatic disease or chemoradiation therapy for primary disease.
Definitive diagnosis of mEC or metastatic adenocarcinoma of GEJ Siewert
Classification Type I will be made by integrating the histopathological data within the
context of clinical and radiographic data.
Patients who received chemotherapy in the adjuvant setting are not allowed.
x Absence of HER2 expression documented as ISHnegative on previously collected and
assessed tumor tissue upon initial diagnosis of disease. HER2 negativity will be
retrospectively confirmed by central laboratory testing after enrollment.
HER2-negative status will be determined on the basis of archival or, if not available,
pre-screening biopsy material and defined as an ISH non-amplified (ratio of HER2 to
CEP17 2.0 or single probe average HER2 gene copy number 4 signals/cell)
or
IHC 0 or IHC 1
(if more than one test result is available and not all results meet the
inclusion criterion definition, all results should be discussed with the Medical Monitor to
establish eligibility of the patient)
x Willing to undergo biopsy if archival tissue is not available or if archival tissue was taken
!6 months from Cycle 1, Day 1

General Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:
General Exclusion Criteria
x Any approved anti-cancer therapy, including chemotherapy, hormonal therapy,
or radiotherapy, or herbal medicines intended as anti-cancer therapy, within 3 weeks prior
to initiation of study treatment; the following are, however, allowed:
Hormone-replacement therapy
Palliative radiotherapy for bone metastases ! 2 weeks prior to Day 1
x Bisphosphonate therapy for symptomatic hypercalcemia
Use of bisphosphonate therapy for other reasons (e.g., bone metastasis
or osteoporosis) is allowed.
x Uncontrolled pleural effusion, pericardial effusion, or ascites
Patients with indwelling catheters (e.g., PleurX£
) are allowed.
x Uncontrolled tumor-related pain
Patients requiring narcotic pain medication must be on a stable regimen at study entry.
Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement)
amenable to palliative radiotherapy should be treated prior to start of study treatment.
Patients should be recovered from the effects of radiation. There is no required
minimum recovery period.
Asymptomatic metastatic lesions whose further growth would likely cause functional
deficits or intractable pain (e.g., epidural metastasis that is not presently associated with
spinal cord compression) should be considered for loco-regional therapy if appropriate
prior to the start of study treatment.
x Uncontrolled hypercalcemia (! 1.5 mmol/L ionized calcium or calcium ! 12 mg/dL or
corrected serum calcium ! ULN) or symptomatic hypercalcemia requiring continued use of
bisphosphonate therapy
Patients who are receiving denosumab must discontinue denosumab use and replace it
with a bisphosphonate instead while in the study. There is no required minimum
washout period for denosumab.
Patients who are receiving bisphosphonate therapy specifically to prevent skeletal
events and who do not have a history of clinically significant hypercalcemia are eligible.
x Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis,
cirrhosis, fatty liver, and inherited liver disease
NOTE: Does not apply to patients in Arm A and Arm D (see Arm A and
Arm Dspecific inclusions)
x Known primary CNS malignancy or untreated or active CNS metastases (progressing or
requiring anticonvulsants or corticosteroids for symptomatic control)
Patients with a history of treated CNS metastases are eligible, provided they meet all of
the following criteria:
Measurable disease outside the CNS
No evidence of interim progression between the completion of CNS-directed
therapy and the screening radiographic study
No history of intracranial hemorrhage or spinal cord hemorrhage
No ongoing requirement for dexamethasone as therapy for CNS disease;
anticonvulsants at a stable dose allowed.
Screening CNS radiographic study must be t 4 weeks since completion of
radiotherapy and t 2 weeks since discontinuation of corticosteroids.
No metastases to brain stem, midbrain, pons, medulla, or within 10 mm of the optic
apparatus (optic nerves and chiasm)
x Pregnant or lactating, or intending to become pregnant during the study
x Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or
other recombinant human antibodies
x Inability to comply with study and follow-up procedures
x History of autoimmune disease including, but not limited to, systemic lupus erythematosus,
rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with
antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Bell’s palsy,
Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
replacement hormone may be eligible.
Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be
eligible.
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic
manifestations only (e.g., patients with psoriatic arthritis) are permitted provided that
they meet the following conditions:
Patients with psoriasis must have a baseline ophthalmologic examination to rule
out ocular manifestations
Rash must cover less than 10% of body surface area
Disease is well controlled at baseline and only requiring low potency topical
steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%,
flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
No acute exacerbations of underlying condition within the last 12 months (not
requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate, retinoids,
biologic agents, oral calcineurin inhibitors, high potency or oral steroids)
x History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis,
organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or
evidence of active pneumonitis on screening chest computed tomography (CT) scan
History of radiation pneumonitis in the radiation field (fibrosis) is permitted
x Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that contraindicates
the use of an investigational drug or that may affect the interpretation of the results or
render the patient at high risk from treatment complications
x Positive test for HIV
x Active hepatitis B (chronic or acute), or hepatitis C
Does not apply to patients in Arm A and Arm D (see Arm A and Arm D-specific
inclusions)
Patients with past or resolved hepatitis B infection (defined as having a negative HBsAg
test and a positive hepatitis B core antigen [anti-HBc] test) are eligible.
Patients who test positive for HCV antibody are eligible only if polymerase chain reaction
(PCR) is negative for HCV RNA.
x Active tuberculosis
x Severe infections within 4 weeks prior to Day 1, including but not limited to hospitalization
for complications of infection, bacteremia, or severe pneumonia
x Signs or symptoms of significant infection within 2 weeks prior to Day 1
x Received oral or intravenous (IV) antibiotics within 2 weeks prior to Cycle 1, Day 1
Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection
or chronic obstructive pulmonary disease) are eligible.
x Significant cardiovascular disease, such as New York Heart Association cardiac disease
(Class II or greater), myocardial infarction within 3 months prior to prior to Day 1, unstable
arrhythmias, or unstable angina
Patients with a known left ventricular ejection fraction (LVEF)  40% will be excluded.
Patients with known coronary artery disease, congestive heart failure not meeting the
above criteria, or LVEF  50% must be on a stable medical regimen that is optimized in
the opinion of the treating physician, in consultation with a cardiologist if appropriate.
x History of stroke, prolonged reversible ischemic neurological deficit or transient ischemic
attack within 6 months prior to Day 1
x Major surgical procedure within 28 days prior to Day 1 or anticipation of need for a major
surgical procedure during the course of the study
Placement of central venous access catheter(s) (e.g., port or similar) is not considered
a major surgical procedure and is therefore permitted.
x Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or
anticipation that such a live attenuated vaccine will be required during the study
Influenza vaccination should be given during influenza season only (approximately
October to March in the Northern Hemisphere and approximately April through
September in the Southern Hemisphere). Patients must agree not to receive live,
attenuated influenza vaccine (e.g., FluMist£
) within 28 days prior to the start of study
treatment, during treatment, or within 5 months after the last dose of atezolizumab.
x Any serious medical condition or abnormality in clinical laboratory tests that, in the
investigator’s judgment, precludes the patient’s safe participation in and completion of the
study
x Malignancies other than pancreatic carcinoma within 2 years prior to study start, with the
exception of those with a negligible risk of metastasis or death (e.g., expected 5-year
OS! 90%) treated with expected curative outcome (such as adequately treated carcinoma
in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated
surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
Exclusion Criteria Related to Medications
x Prior treatment with anticytotoxic T lymphocyteassociated antigen 4, antiprogrammed
death1 (PD-1), or antiPD-L1 therapeutic antibody
x Treatment with systemic immunostimulatory agents (including but not limited to IFN-D and
IL-2) within 6 weeks or five half-lives of the drug, whichever is longer, prior to screening
x Treatment with any investigational agent within 4 weeks prior to screening (or within five
half-lives of the investigational product, whichever is longer)
x Treatment with systemic corticosteroids or other immunosuppressive medications (including
but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide,
and antitumor necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1, Day 1
Patients who have received acute, low-dose, systemic immunosuppressant medications
(e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study after
discussion with and approval by the Medical Monitor.
Patients with a history of allergic reaction to IV contrast requiring steroid pre-treatment
should have baseline and subsequent tumor assessments performed using magnetic
resonance imaging.
The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for
patients with orthostatic hypotension, chronic obstructive pulmonary disease, or
adrenocortical insufficiency is allowed.
x History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or
humanized antibodies or fusion proteins
x Patients with prior allogeneic bone marrow transplantation or prior solid organ
transplantation
x Known allergies to oxaliplatin (or other platinum agents), leucovorin, 5-FU, nab-paclitaxel
(or other taxanes) or gemcitabine
Bevacizumab and Vanucizumab-Specific Exclusions (Arms A, B, and D)
x Inadequately controlled arterial hypertension (defined as systolic blood pressure
[BP] ! 150 mmHg and/or diastolic BP ! 100 mmHg), based on an average of t3 BP
readings on t2 sessions
Anti-hypertensive therapy to achieve these parameters is allowable.
x Prior history of hypertensive crisis or hypertensive encephalopathy
x Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent
peripheral arterial thrombosis) within 6 months prior to Day 1
x History of hemoptysis (t 2.5 mL of bright red blood per episode) within 1 month prior to
Day 1
x Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic
anticoagulation)
x Current or recent (within 10 days of first dose of study treatment) use of aspirin
(! 325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol
x Current or recent (within 10 days prior to study treatment start) use of full-dose oral or
parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic)
purpose
Prophylactic anticoagulation for the patency of venous access devices is allowed
provided the activity of the agent results in an INR  1.5 u ULN and aPTT is within
normal limits within 14 days prior to Day 1.
Prophylactic use of low molecular-weight heparin (i.e., enoxaparin 40 mg/day)
is allowed.
x Core biopsy or other minor surgical procedure, excluding placement of a vascular access
device, within 3 days prior to the first dose of bevacizumab or vanucizumab
x History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or
intra-abdominal abscess within 6 months prior to Day 1
x History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including
sub-occlusive disease related to the underlying disease or requirement for routine
parenteral hydration, parenteral nutrition, or tube feeding within 6 months prior to Day 1 of
Cycle 1. Patients with signs and/or symptoms of sub-occlusive or occlusive syndrome, or
intestinal obstruction at time of initial diagnosis may be enrolled if they had received
definitive (surgical) treatment for symptom resolution.
x Evidence of abdominal free air that is not explained by paracentesis or recent
surgical procedure
x Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
x Proteinuria, as demonstrated by urine dipstick or ! 1.0 g of protein in a 24-hour
urine collection
All patients with t2+ protein on dipstick urinalysis at baseline must undergo a 24-hour
urine collection for protein.
x Metastatic disease that involves major airways or blood vessels, or centrally located
mediastinal tumor masses ( 30 mm from the carina) of large volume. Patients with HCC
(Arm A and Arm D) and vascular invasion of the portal or hepatic veins may be enrolled.
x History of intra-abdominal inflammatory process within 6 months prior to Day 1 of Cycle 1,
including but not limited to peptic ulcer disease, diverticulitis, or colitis
x Radiotherapy within 28 days and abdominal/ pelvic radiotherapy within 60 days prior to
Day 1 of Cycle 1, except palliative radiotherapy to bone lesions within 7 days prior to Day 1
of Cycle 1
x Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to
Day 1 of Cycle 1, or abdominal surgery, abdominal interventions or significant abdominal
traumatic injury within 60 days prior to Day 1 of Cycle 1 or anticipation of need for major
surgical procedure during the course of the study or non-recovery from side effects of any
such procedure
x Chronic daily treatment with a nonsteroidal anti-inflammatory drug (occasional use for the
symptomatic relief of medical conditions such as headache or fever is allowed)
Exclusions specific to Hepatocellular Carcinoma (Arms A and D)
x Patients with untreated or incompletely treated varices with bleeding or high-risk for
bleeding
Patients must undergo an esophagogastroduodenoscopy (EGD) and all size of varices
(small to large) must be assessed and treated per local standard-of-care prior to
enrollment
x Treatment with any HCV anti-viral therapy within 4 weeks prior to Cycle 1, Day 1
x Moderate or severe ascites
x Hepatic encephalopathy
x Co-infection of HBV and HCV
Patients with a history of HCV infection but who are negative for HCV RNA by PCR will
be considered non-infected with HCV
Exclusions Specific to Arm B (Gastric Cancer)
x HER2 expression as defined by ISH positive and/or 3+
by immunohistochemistry (IHC)
x Prior treatment with an oxaliplatin-containing regimen
Oxaliplatin ! 12 months prior to the diagnosis of metastatic disease is permitted.
x Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene
polymorphism predisposing the patient for 5-FU toxicity
x Previous antiangiogenic therapy
x Ongoing treatment for epilepsy
Exclusions Specific to Arm C (Metastatic Pancreatic Cancer)
x Patients with only locally advanced disease
x Presence of islet cell neoplasms
Exclusions Specific to Arm E (Metastatic Esophageal Cancer)
x HER2 expression as defined by ISH positive and/or 3+ by IHC
x Prior chemotherapy treatment, including radio-sensitization in pre- and post-operative settings.