A Study of Anti-VEGFR-3 Monoclonal Antibody IMC-3C5 in Subjects With Advanced Solid Tumors

Phase 1 Study of the Anti-VEGFR-3 Monoclonal Antibody IMC-3C5 in Subjects With Advanced Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy is Available

A dose escalation study to determine the safety and maximum tolerated dose (MTD) of IMC-3C5 in subjects with advanced solid tumors that are refractory to standard therapy or for which no standard therapy is available.

This multicenter study will enroll approximately 40 participants. The actual sample size will vary depending on how many participants are needed to obtain at least 3 complete participants per cohort.

IMC-3C5 will initially be administered once every week (Cohorts 1-4) in a dose escalated manner. The starting dose will be 5 mg/kg weekly (Cohort 1). Dose escalation will proceed to 10 mg/kg (Cohort 2), 20 mg/kg (Cohort 3), and 30 mg/kg (Cohort 4). Based on an analysis of the safety and pharmacokinetic profile of weekly dosing, participants may be enrolled sequentially into 2 every-other-week dose cohorts (Cohorts 5-6, 20 mg/kg and 30 mg/kg). Intermediate doses may also be used.

Inclusion Criteria:

1. Participant has histologic or cytologic confirmation of cancer
2. Participant has an advanced solid tumor that is refractory to standard therapy or for which no standard therapy is available
3. Participant has measurable or nonmeasurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
4. Participant has not received prior chemotherapy or prior treatment with an investigational agent or device within 28 days prior to enrollment(hormone therapy is acceptable)
5. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1, or 2
6. Participant has adequate hematologic, hepatic, renal, and coagulation function
7. Participant has a life expectancy greater than 3 months
8. Participant agrees to use adequate contraception during the study period and for 12 weeks after last dose of investigational agent

Exclusion Criteria:

1. Participant has a known sensitivity to monoclonal antibodies or other therapeutic proteins, or to agents of similar biologic composition as IMC-3C5
2. Participant has received treatment with any monoclonal antibodies including bevacizumab within 6 weeks prior to enrollment
3. Participant has undergone a major surgical procedure, radiation therapy, open biopsy, or has experienced a significant injury within 28 days prior to enrollment
4. Participant has an ongoing or active infection (except as outlined in Exclusion Criterion #11), congestive heart failure, active bleeding or any other serious uncontrolled medical disorder
5. Participant has known or suspected untreated brain or leptomeningeal metastases
6. Participant has uncontrolled hypertension
7. Participant has received an organ transplant
8. Participant has a serious or nonhealing wound, ulcer, or bone fracture
9. Participant has experienced an arterial or venous thromboembolic event within 6 months prior to enrollment
10. Participant currently has peripheral edema requiring diuresis or anasarca
11. Participant has Human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), except subjects who have been on a stable antiviral regimen for at least 12 weeks, have a viral load of < 50 copies/mL, and a CD4 count of ≥ 200 cells/mm3
12. Participant is currently using or has received a thrombolytic agent within 28 days prior to enrollment
13. Participant is receiving aspirin at a dose higher than 325 mg per day or full-dose anticoagulation
14. Participant if female, is pregnant or is lactating