A Phase 1b Study of Demcizumab Plus Pembrolizumab in Locally Advanced or Metastatic Solid Tumors

This is an open-label, Phase 1b dose escalation and expansion study of demcizumab plus
pembrolizumab designed to evaluate the safety, efficacy and pharmacokinetics of demcizumab in
combination with pembrolizumab in patients with advanced or metastatic solid tumors. This
study consists of a screening period, a treatment period and a post-treatment follow up
period in which patients will be followed for survival for approximately 12 months. Patients
will be enrolled in two stages: a dose-escalation stage and an expansion phase.

Approximately 42 patients will be enrolled in this study at approximately 10 study centers in
the United States (U.S) and Europe.

Inclusion Criteria:

1. Measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1

2. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue, either fresh
core-needle-biopsied or archived

3. Age >21 years

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

5. Adequate organ and marrow function

6. For women of childbearing potential and men with partners of childbearing potential,
agreement (by patient and/or partner) to use two effective forms of contraception from
study entry through at least 6 months after the termination visit.

7. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Treatment with any anti-cancer therapy, including radiotherapy, chemotherapy, biologic
therapy, or herbal therapy within 3 weeks or 5 half-lives (for systemic agents)
whichever is shorter

2. Receiving any other investigational agents or any other anti-cancer therapy

3. Active infections requiring antibiotics

4. Patients with brain metastases (treated or untreated) leptomeningeal disease,
uncontrolled seizure disorder, or active neurologic disease

5. History of interstitial lung disease or active, non-infectious pneumonitis that
required oral or intravenous corticosteroids

6. Prior radiation to the chest wall or mediastinum if the radiation field involves the
heart

7. Significant intercurrent illness that will limit the patient's ability to participate
in the study or may result in their death over the next 18 months

8. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to enrollment, or anticipation of need for major surgical procedure during the
course of the study

9. Pregnant or nursing women

10. New York Heart Association Classification II, III, or IV

11. Acute prior study treatment related toxicity (except alopecia) that has not resolved
to Grade < or = to 1 unless it has been deemed stable by the investigator

12. Inability to comply with study and follow up procedure