Study of PEGPH20 With Cisplatin (CIS) and Gemcitabine (GEM); PEGPH20 With Atezolizumab, CIS, and GEM; and CIS and GEM Alone in Participants With Previously Untreated, Unresectable, Locally Advanced, or Metastatic Intrahepatic and Extrahepatic Cholangiocarcinoma and Gallbladder Adenocarcinoma

The study will have a Run-in portion and an Expansion portion. The Run-in portion will be
used to evaluate the safety profile of the PEGCISGEM and PEGCISGEMATEZO treatments prior to
evaluating the efficacy and safety of PEGCISGEM and PEGCISGEMATEZO treatments compared with
CISGEM treatment in the Expansion portion of the study. Treatment in both portions of the
study will continue until death, withdrawal of consent from the study, disease progression,
or unacceptable toxicity.

Inclusion Criteria:

For both portions of the study, participants must satisfy all of the following inclusion
criteria to be enrolled in the study:

- Written Institutional Review Board/Ethics Committee-approved informed consent form
(ICF), signed by participant or legally authorized representative.

- Participants must be determined to have histologically confirmed unresectable, locally
advanced or metastatic adenocarcinoma of the intra- and/or extra-hepatic bile ducts
and/or gallbladder. Participants must have sufficient tissue with architectural
integrity, including tumor and associated stroma, available for retrospective
biomarker testing.

- One or more lesions measurable on computed tomography (CT) scan/magnetic resonance
imaging (MRI) scan per Response Evaluation Criteria in Solid Tumors (RECIST) version
1.1 (v1.1).

- Participants having Eastern Cooperative Oncology Group (ECOG) Performance Status of 0
to 1.

- Life expectancy ≥3 months.

- Males and females aged ≥18 years.

- Screening clinical laboratory values within pre-determined parameters

- Female participants of childbearing potential (WOCBP) must have a negative urine or
serum pregnancy test within 7 days before Day 1 (first dose of study medication).

- For WOCBP and for men, agreement to use a highly effective contraceptive method from
the time of screening throughout the study until 5 months (WOCBP) or 6 months (men)
after administration of the last dose of any study medication. Highly effective
contraceptive methods consist of prior sterilization, intrauterine device (IUD),
intrauterine hormone releasing system (IUS), oral or injectable contraceptives,
barrier methods, and/or true sexual abstinence.

Exclusion Criteria:

Participants are ineligible for enrollment if they meet any of the following exclusion
criteria:

- Clinical evidence of deep vein thrombosis or pulmonary embolism present during the
screening period

- New York Heart Association Class III or IV cardiac disease, atrial fibrillation,
unstable angina, or myocardial infarction within the past 12 months before screening.

- Participants with known brain metastases

- History of cerebrovascular accident or transient ischemic attack

- History of active bleeding within the last 3 months prior to screening requiring
transfusion.

- Participants must have received no previous radiotherapy, surgery, chemotherapy or
investigational therapy for treatment of metastatic or locally advanced disease.

- Active hepatitis B virus (HBV) infection, defined as having a positive hepatitis B
surface antigen (HBsAg) test at screening

- Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody
test at screening

- History of:

1. 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 radiation pneumonitis
in the radiation field (fibrosis) is permitted.

2. Or known cases of hepatobiliary diseases (e.g., primary biliary cholangitis,
primary sclerosing cholangitis, history of immune-mediated cholangitis);

Participants with cholangitis attributed to infectious etiology (e.g., ascending
cholangitis, bacterial cholangitis) are eligible if the infection has been fully
resolved prior to the screening visit.

3. Or known cases of drug-induced hepatobiliary toxicities.

- Active or history of autoimmune diseases

- Uncontrolled hypercalcemia