A Multiple-Ascending-Dose Study of the Safety and Tolerability of REGN421(SAR153192) in Patients With Advanced Solid Malignancies

Inclusion Criteria:

1. Male or female 18 years of age or older

2. Histologically diagnosis of advanced solid malignancy, with no standard therapeutic
options of proven benefit.

3. Patients with measurable or non-measurable disease

4. At least 6 weeks must have elapsed since the last dose of bevacizumab (AvastinTM)

5. At least 4 weeks must have elapsed since the last major surgery

6. For women of childbearing potential, a negative urine pregnancy test at the screening
visit

7. Willingness to use adequate contraception during the full course of the study.
Systemic hormonal contraceptive agents are excluded

8. Willing, committed, and able to return for ALL clinic visits and complete all
study-related procedures.

9. Able to read, understand and willing to sign the informed consent form

Exclusion Criteria:

1. Medical history of myocardial infarction or cardiomyopathy

2. Unstable angina

3. NYHA class II - IV congestive heart failure

4. Patients under treatment with more than 2 antihypertensive medications

5. History of bleeding peptic ulcer disease, erosive gastritis, intestinal perforation,
or clinically significant GI hemorrhage within 6 months of study drug administration

6. Diabetic retinopathy

7. Patients requiring anticoagulation

8. Hypersensitivity to doxycycline or related compounds