Phase 1b Open-Label Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) With Pembrolizumab

This study includes a dose-escalation phase (completed in Nov-2016) to assess the safety and
tolerability of PEGPEM combined with pembrolizumab (Keytruda®) and find the recommended Phase
2 dose (RP2D). The study also includes a dose-expansion phase to assess the efficacy, safety,
and tolerability of PEGPEM in stage III b/IV NSCLC and relapsed/refractory GAC participants.
The study will include approximately 51 HA-high participants (30 NSCLC and 21 GAC
participants) in the dose-expansion phase on the obtained RP2D from the dose-escalation phase
of the study.

Inclusion Criteria:

- Dose Expansion: Histologically confirmed and documented, previously untreated or
treated stage IIIB or IV NSCLC having failed no more than 1 previous platinum
containing chemotherapy regimen for locally-advanced or metastatic disease or
relapsed/refractory locally advanced or metastatic gastric adenocarcinoma having
failed no more than 2 previous chemotherapy regimen for locally advanced or metastatic
disease. Participants with NSCLC who are known to be epidermal growth factor receptor
(EGFR)-mutation positive must have received an EGFR inhibitor and participants known
to be anaplastic lymphoma kinase (ALK)-mutation positive must have received an ALK
inhibitor.

Prior to enrollment, confirmation of the following must be obtained:

• For participants in the dose expansion portion of the study, it is mandatory that
available archived tumor tissue in formalin-fixed.

paraffin-embedded (FFPE) block or minimum 10-15 unstained consecutive core biopsy slides
from 1 archival block that meet specific tissue requirements are available.

- For dose expansion: one or more tumors measurable on computed tomography (CT)
scan/magnetic resonance imaging (MRI) scan per RECIST v 1.1., for dose escalation,
participants need only have evaluable disease - Previously irradiated tumors may be
eligible if they have clearly progressed in size.

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

- Life expectancy greater than or equal to (≥) 3 months.

Participants must also satisfy the following inclusion criterion to be enrolled in the dose
expansion portion:

- Participants (NSCLC and gastric adenocarcinoma) must be determined to have HA-high
levels from their tumor biopsies.

- NSCLC and gastric adenocarcinoma participants must have tissue available for
HA-selection and programmed cell death-1 (PD-L1) testing.

Exclusion Criteria:

- Previous treatment with pembrolizumab, nivolumab, or other antibody (anti-)-PD-1 or
PD-1 ligand-antibody (anti-PD-L1) agents.

- New York Heart Association Class III or IV (Appendix D) cardiac disease or myocardial
infarction within the past 12 months before screening, or preexisting atrial
fibrillation.

- Prior history of cerebrovascular accident or transient ischemic attack.

- NSCLC participants with known brain metastases (certain exceptions allowed)

- Gastric adenocarcinoma participants with brain metastases

- History of active bleeding within the last 3 months requiring transfusion

- Anti-angiogenic therapy within the last month

- Participants with known interstitial fibrosis or interstitial lung disease.

- Previous history of pulmonary embolism or pulmonary embolism found on screening exam.

- History of:

1. Pneumonitis that requires oral or IV steroids;

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 autoimmune disease requiring systemic treatment within the past 3 months or
documented history of clinically severe autoimmune disease, or syndrome that requires
systemic steroids or immunosuppressive agents.

- History of another primary cancer within the last 3 years that required treatment,
with the exception of non-melanoma skin cancer, early-stage prostate cancer, or
curatively treated cervical carcinoma in situ.