BNC105P in Combination With Everolimus/Following Everolimus For Progressive Metastatic Clear Cell Renal Cell Carcinoma

Inclusion Criteria:

• Histological or cytological proof of component (any percent) of clear cell RCC (renalcell carcinoma).
• Metastatic or locally advanced unresectable RCC. NOTE: Prior nephrectomy is notmandatory.
• Progressive disease after 1-2 prior VEGF-directed tyrosine kinase inhibitors (TKIs).
• Measurable disease according to RECIST and obtained by imaging within 30 days prior toregistration for protocol therapy.
• Written informed consent and HIPAA authorization for release of personal healthinformation.
• Age > 18 years at the time of consent.
• Females of childbearing potential and males must be willing to use an effective methodof contraception (hormonal or barrier method of birth control; abstinence) from thetime consent is signed until 4 weeks after treatment discontinuation.
• Females of childbearing potential must have a negative pregnancy test within 7 daysprior to registration for protocol therapy.

Exclusion Criteria:

• No active brain metastases. Patients with neurological symptoms must undergo a head CTscan or brain MRI to exclude brain metastasis within 30 days prior to registration onprotocol therapy. NOTE: A patient with prior brain metastasis are eligible if theyhave completed their radiation treatment for brain metastasis ≥30 days prior toregistration for protocol therapy, are off steroids, and are asymptomatic.
• No other currently active malignancy.
• No treatment with any investigational agent within 14 days prior to registration forprotocol therapy. NOTE: If treated with investigational agent within 14 days prior toregistration, AE must be resolved back to baseline.
• Prior cancer treatment must be completed at least 14 days prior to registration forprotocol therapy and the patient must have recovered from the acute toxic effects ofthe regimen. With the exception of Bevacizumab treatment, which must be completed 30days prior to registration for protocol therapy.
• Prior radiation therapy to < 25% of the bone marrow [see bone marrow radiation chartin the study procedure manual (SPM)] allowed if completed within 30 days prior toregistration for protocol therapy.
• Corrected QT interval (QTc) ≤ 450 msec at least 7 days prior to registration forprotocol therapy.
• No clinically significant infections as judged by the treating investigator.
• No liver disease such as cirrhosis, chronic active hepatitis or chronic persistenthepatitis.
• No collecting duct, medullary or sarcomatoid histology.
• No prior treatment with temsirolimus or everolimus in the phase II component of thestudy. NOTE: Prior treatment with these agents is permitted in the phase I componentof the study.
• No use of full dose, therapeutic anti-coagulation with warfarin or relatedanti-coagulants or unfractionated or low molecular weight heparins.
• No uncontrolled hypertension (BP >150/100mmHg despite full doses of 1anti-hypertensive medication).
• No thrombotic event within 6 months (deep vein thrombosis, pulmonary embolism) ofregistration for protocol therapy.
• No grade 2 or greater peripheral neuropathy.