A Study of Recombinant Vaccinia Virus in Combination With REGN2810 for Renal Cell Carcinoma

Inclusion Criteria:

- Histologically or cytologically confirmed metastatic or unresectable clear cell renal
cell carcinoma (ccRCC)

- Measurable disease based on RECIST 1.1 criteria. Tumor lesions situated in a
previously irradiated area are considered measurable if progression has been
demonstrated in such lesions

- Karnofsky performance status of 70-100

- Age ≥20 years old (or appropriate age of consent for the region)

- Adequate hematological, hepatic, and renal function

Exclusion Criteria:

- Known significant immunodeficiency due to underlying illness (e.g., human
immunodeficiency virus [HIV] / acquired immune deficiency syndrome [AIDS]) and/or
immune-suppressive medication including high-dose corticosteroids

- Part 2 only: Prior treatment with any anti-cancer immunotherapy, including therapy
with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent (prior IL-2 or interferon allowed)
. For Part 1: patients are excluded if they were intolerant to anti-PD-1 or anti-PD-L1
targeted therapies

- Major surgery within 4 weeks of study treatment (minor surgical procedures are
allowed)

- Ongoing severe inflammatory skin condition requiring prior medical treatment

- History of eczema requiring prior medical treatment

- Tumor(s) invading a major vascular structure (e.g., carotid artery) or other key
anatomical structure (e.g., pulmonary airway) OR viable central nervous system
malignancy

- Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural
effusions.

- Symptomatic cardiovascular disease, including but not limited to significant coronary
artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure
within the preceding 12 months.

- Asymptomatic cardiovascular disease (current or past history) unless cardiology
consultation and clearance has been obtained for study participation.

- Inability to suspend treatment with anti-hypertensive medication for 48 hours prior to
and 48 hours after all Pexa-Vec treatments

- Use of interferon/pegylated interferon (PEG-IFN) or ribavirin that cannot be
discontinued within 14 days prior to any Pexa-Vec dose

- Known active Hepatitis B or Hepatitis C