Phase II Single Arm Study of IMC-1121B in Patients With Metastatic Renal Cell Carcinoma With Disease Progression on or Intolerance to Tyrosine Kinase Inhibitor Therapy

Inclusion Criteria

Inclusion Criteria

1. The patient has histologically or cytologically confirmed clear cell RCC

2. The patient is ≥ 18 years of age

3. The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) of
0-1 or Karnofsky Performance Status (KPS) ≥ 80%

4. The patient has had a prior nephrectomy (as therapy for RCC)

5. The patient has metastatic RCC

6. The patient has a life expectancy of > 3 months

7. The patient has measurable disease as defined by Response Evaluation Criteria in
Solid Tumors (RECIST)

8. The patient has received prior therapy with a TKI (sunitinib and/or sorafenib) with
either disease progression on TKI therapy (progression within 60 days of the last
dose of TKI) or intolerance to TKI (unable to continue therapy because of
side-effects). A patient with progression during a protracted treatment break is not
eligible unless the patient has had progression or intolerance as defined above

9. The patient has resolution of all clinically significant toxic effects of prior
cancer therapy to grade ≤ 1 by the National Cancer Institute Common Terminology
Criteria for Adverse Events, version 3.0 (NCI-CTCAE)

10. The patient has adequate hematological functions (absolute neutrophil count [ANC] ≥
1500 cells/mL, hemoglobin ≥ 9 g/dL and platelets ≥ 100,000 cells/mL)

11. The patient has adequate hepatic function (bilirubin within normal limits [WNL],
aspartate transaminase [AST] and/or alanine transaminase [ALT] ≤ 2.5 times the upper
limit of normal [ULN], or ≤ 5.0 times the ULN if the transaminase elevation is due to
liver metastases)

12. The patient has normal renal function or mild renal dysfunction (creatinine ≤ 2.2
mg/dL)

13. The patient's urinary protein ≤ 1+ on dipstick or routine urinalysis ([UA]; if urine
dipstick or routine analysis is ≥ 2+, a 24-hour urine for protein must demonstrate <
1000 mg of protein in 24 hours to allow participation in the study)

14. The patient must have adequate coagulation function as defined by International
Normalized Ratio (INR) ≤ 1.8 and a partial thromboplastin time (PTT) ≤ 1.5 X ULN.
Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulant
or low molecular weight (LMW) heparin and if on warfarin must have a INR between 2
and 3 and have no active bleeding or pathological condition that carries a high risk
of bleeding (eg, tumor involving major vessels or known varices)

15. The patient is able to provide informed written consent

16. The patient, if sexually active, is postmenopausal (last menstrual period > 2 years
prior to study), surgically sterile, or is using effective method of contraception in
the opinion of the investigator

17. The patient, if female, must have a negative serum pregnancy test upon entry into
this study

18. The patient has a normal thyroid stimulating hormone (TSH) value. Patients with an
abnormal TSH may be eligible provided they meet all other eligibility criteria and
have ECOG performance status 0-1. Patients with an abnormal TSH value require a full
thyroid evaluation prior to enrollment. Endocrinology consultation may be performed
at the discretion of the investigator

19. The patient has serum calcium within normal limits

Exclusion Criteria

1. The patient has received prior treatment with bevacizumab

2. The patient has known brain or leptomeningeal metastases

3. The patient has received >2 prior cytotoxic chemotherapy regimens for RCC

4. The patient has received antitumor therapy (biologic agents, major surgery, or
investigational agent) within 28 days prior to enrollment on study. The patient has
received radiation therapy within 14 days prior to enrollment on study. Patients with
metastasis in weight bearing bones at high risk for pathologic fracture may
participate provided that appropriate surgical intervention and/or radiation therapy
is undertaken and completed at least 28 days prior to enrollment

5. The patient has received > 1 prior bioimmunotherapy regimens (defined as either
interleukin-2 or interferon alpha given as monotherapy, concurrently, or sequentially
as planned)

6. The patient has a concurrent active malignancy other than adequately treated
non-melanomatous skin cancer or other non-invasive carcinoma or in situ neoplasm. A
patient with previous history of malignancy is eligible, provided that he/she has
been disease free for > 3 years

7. The patient has a nonhealing wound or ulcer

8. The patient has a known alcohol or drug dependency

9. The patient is pregnant or breastfeeding

10. The patient has a coexisting medical or psychiatric problem of sufficient severity to
limit compliance with the study and/or increase the risks associated with study
participation or study drug administration or interfere with the interpretation of
study results

11. The patient has an ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia,
psychiatric illness/social situations, or any other serious uncontrolled medical
disorders in the opinion of the investigator

12. The patient has known human immunodeficiency virus infection or acquired
immunodeficiency syndrome-related illness