A Randomized, Open-Label, Phase 3 Study of Nivolumab (BMS-936558) vs. Everolimus in Subjects with Advanced or Metastatic Clear-Cell Renal Carcinoma Who Have Received Prior Anti-Angiogenic Therapy.
CA209025 is a Phase 3, randomized, open-label study of BMS-936558 vs everolimus in subjects with advanced or metastatic renal cell carcinoma (RCC) who received prior anti-angiogenic therapy. Among all agents approved for advanced or metastatic RCC, only everolimus is approved specifically for use after the failure of treatment with
anti-angiogenic therapy. This study will allow for direct comparison of the duration of overall survival (OS) provided by BMS-936558 vs everolimus. If BMS-936558 has an acceptable safety profile and is shown to improve OS vs everolimus, this study may support the approval of BMS-936558 in subjects with advanced or metastatic RCC who
have received prior anti-angiogenic therapy, thereby providing another therapeutic option for this patient population.
1) Signed Written Informed Consent
a) Willing and able to provide informed consent.
2) Target Population
a) Men and women >= 18 years of age.
b) Histological confirmation of RCC with a clear cell component.
c) Advanced or metastatic RCC.
d) Measurable disease as defined by RECIST 1.1 criteria
e) Must have received one or two prior anti-angiogenic therapy regimens (including, but not limited to, sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and bevacizumab) in the advanced or metastatic setting. Prior cytokine therapy (eg, IL-2, IFN-(RegisteredTM)), vaccine therapy, or treatment with cytotoxics is also allowed.
f) Must have received no more than three total prior systemic treatment regimens in the advanced or metastatic setting, and must have evidence of progression on or after the last treatment regimen received and within 6 months prior to study enrollment.
g) Karnofsky Performance Score (KPS) >= 70%.
h) Tumor tissue (FFPE archival or recent acquisition) must be received by the central vendor (block or unstained slides) for correlative studies in order to randomize a subject to study treatment.
3) Age and Reproductive Status
a) Women of childbearing potential (WOCBP) must use method(s) of contraception based on the tables in Appendix 3. For a teratogenic study drug and/or when there is insufficient information to assess teratogenicity (preclinical studies have not been done), a highly effective method(s) of contraception (failure rate of less than 1% per year) is required. The individual methods of contraception should be determined in consultation with the investigator. WOCBP must follow
instructions for birth control when the half life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 30 days plus the time required for the investigational drug to undergo five half lives.
b) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product.
c) Women must not be breastfeeding.
d) Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men that are sexually active with WOCBP must follow instructions for birth control when the half life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 90 days plus the time required for the investigational drug to
undergo five half lives.
4) Physical and Laboratory Test Findings
a) Serum creatinine <= 1.5 x ULN OR CrCl >= 40 mL/min (measured or calculated using the Cockcroft-Gault formula):
Female CrCl = (140 - age in years) x weight in kg x 0.85/72 x serum creatinine in mg/dL
Male CrCl = (140 - age in years) x weight in kg x 1.00/72 x serum creatinine in mg/dL