A Study to Evaluate MEDI5752 and Axitinib in Subjects With Advanced Renal Cell Carcinoma

Inclusion Criteria:

• Age ≥ 18 at the time of screening
• Body weight > 35 kg
• Written informed consent
• Histologically or cytologically proven advanced RCC with clear cell component
• Advanced RCC not previously treated in that setting
• Provision of tumor material (≥ 5 unstained slides or tissue block) from an archival or fresh tissue sample if clinically feasible
• ECOG performance status of 0 or 1
• Subjects must have at least 1 measurable lesion according to RECIST v1.1
• Life expectancy ≥ 12 weeks
• Adequate organ and marrow function
• Female subjects of childbearing potential must have negative pregnancy test at screening and prior to each administration of investigational product, and must use at least one highly effective method of contraception.

Exclusion Criteria:

• Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
• Concurrent enrollment in another clinical study, unless it is an observational study.
• Previous treatment with mTOR inhibitors, PD-1, PD-L1, or CTLA-4 inhibitors for RCC or any other immune checkpoint inhibitors
• Previous treatment with axitinib; other VEGF TKIs used in the adjuvant setting are allowed if last dose > 6 months prior to the first dose of investigational product
• History of active primary immunodeficiency:
• History of organ transplant
• Active or prior documented autoimmune or inflammatory disorders
• Current or prior use of immunosuppressive medication within 14 days prior to the first dose of investigational product.
• Has poorly controlled hypertension defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg.
• Thromboembolic (arterial or venous) events within previous 6 months
• Any concurrent therapy for cancer
• Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product
• Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s)
• Untreated or progressive CNS metastatic disease, any leptomeningeal disease, or cord compression
• History of another primary malignancy
• Unresolved toxicities from previous anticancer therapy
• Major surgery within 4 weeks prior to enrollment or radiation therapy within 2 weeks prior to enrollment,
• Female subjects who are pregnant or breastfeeding as well as male or female subjects of reproductive potential who are not willing to employ one highly effective method of birth control as described in inclusion criteria
• History of arrhythmia which is symptomatic or requires treatment symptomatic or uncontrolled atrial fibrillation despite treatment
• Uncontrolled intercurrent illness within the last 6 months prior to enrollment
• Clinically significant gastrointestinal abnormality
• Evidence of inadequate wound healing
• Current use or anticipated need for treatment with drugs or foods that are known strong CYP3A4/5 inhibitors