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

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