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
* 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.
* Strongly recommend nonsterilized male partners of female subjects of childbearing potential use a male condom plus spermicide from screening to 7.6 months after the last dose of MEDI5752 and 30 days after the last dose of lenvatinib.
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 inhibitor
* Previous treatment with VEGF inhibitors
* Evidence of the following infections: active infection including tuberculosis, human immunodeficiency virus, chronic or active hepatitis B or chronic or active hepatitis C
* 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.
* Poorly controlled blood pressure (BP) defined as systolic BP ≥ 140/90 mmHg at screening and not able to be controlled prior to Cycle 1 Day 1 and any change in antihypertensive medications within 1 week prior to Cycle 1 Day 1.
* 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 or has not recovered from AEs due to prior treatment
* Female subjects must not breastfeed and must not donate, or retrieve for their own use, ova from screening to 3 months after the last dose of MEDI5752 and 30 days after the last dose of lenvatinib.
* History of arrhythmia which is symptomatic or requires treatment, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
* Uncontrolled intercurrent illness within the last 6 months prior to enrollment
* Clinically significant gastrointestinal abnormality
* Serious nonhealing wound, ulcer, or bone fracture
* Has clinically significant hemoptysis (at least 0.5 teaspoon of bright red blood) or tumor bleeding within 2 weeks before the first dose of investigational product
* Radiographic evidence of major blood vessel invasion/infiltration/encasement
