Dose-Finding, Safety and Efficacy Study of RX-0201 Plus Everolimus in Metastatic Renal Cell Cancer

A Multicenter, Open-label, Phase 1b/2 Study to Evaluate the Safety and Efficacy of RX-0201 in Combination With Everolimus to Treat Subjects With Advanced Renal Cell Carcinoma

The purpose of this study is to determine the maximum tolerated dose of RX-0201, up to a target dose of 250 mg/m^2/day, when given in combination with everolimus (Stage 1), and to assess the safety and efficacy of RX-0201 plus everolimus, in subjects with metastatic renal cell cancer (Stage 2).

This multi-center, open-label, randomized, parallel group study of RX-0201 in combination with everolimus, versus everolimus alone to treat subjects with advanced renal cell carcinoma will be conducted in 2 stages. Stage 1 will be an open-label, dose-escalation study of RX-0201 to identify a safe and tolerable dose of RX-0201 up to a target dose of 250 mg/m^2/day when given in combination with everolimus. Stage 2 will be a randomized, open-label, 2-arm study of RX-0201 in combination with everolimus versus everolimus alone. Subjects will receive RX-0201, at the dose identified in Stage 1, in combination with everolimus or everolimus alone, for up to 8 cycles to determine safety and efficacy of the combination.

Inclusion Criteria:

• Males and females ≥ 18 years of age at screening
• Histological or cytological diagnosis of renal cell cancer with a clear-cell component
• Measurable or evaluable disease defined by Response Evaluation Criteria for Solid Tumors (RECIST) ver. 1.1
• Must have received at least one course of therapy with a VEGFR-targeting tyrosine kinase inhibitor (eg, sorafenib, sunitinib, axitinib, pazopanib or tivozanib) and progressed within 6 months of planned first dose of study treatment
• ECOG performance status of 0,1 or 2
• Life expectancy > 3 months
• Provide written informed consent

Exclusion Criteria:

• Brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 3 months before planned first dose of study drug
• Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before planned first dose of study drug. Systemic treatment with radionuclides within 6 weeks before planned first dose of study drug. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Prior treatment with everolimus, or any other specific or selective TORC1/PI3K/AKT inhibitor (eg, temsirolimus)
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before planned first dose of study drug
• Receipt of any type of anticancer antibody (including investigational antibody) within 4 weeks before planned first dose of study drug
• Taking strong inducers or inhibitors of CYP450s for subjects receiving everolimus
• Chronic treatment with corticosteroids or other immunosuppressive agents
• Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors
• Subjects with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients
• Major surgery within 2 months before planned first dose of study drug
• Myocardial infarction within the previous 6 months before planned first dose of study drug
• Active infection requiring parenteral antibiotics within 2 weeks before planned first dose of study drug
• Diagnosis of another malignancy within 2 years before planned first dose of study drug, except for superficial skin cancers, or localized, low grade tumors
• Prior or current history of hepatitis B, hepatitis C or human immunodeficiency virus
• Sexually active fertile subjects (male and female) must agree to use medically accepted methods of contraception during the course of the study and for 30 days after the last dose of study treatment