Molecular Residual Disease (MRD) Guided Adjuvant ThErapy in Renal Cell Carcinoma (RCC) (MRD GATE RCC)

Inclusion Criteria: Participants are eligible to be included in the study only if all the following criteria apply. Type of Participant and Disease Characteristics Must have histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features. Diagnosis of RCC with clear cell component is to be made by the investigator and does not require central histology review. Molecular Residual Disease Patients must have at least ONE available assessment of molecular residual disease by the Signatera® (Natera Inc.) assay performed within the last 90 days prior to enrollment in study. Demographics Be ≥18 years of age on the day of signing informed consent. Female Participants: Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study drug. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant. Male Participants: Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of trial therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant. Informed Consent The participant provides written informed consent for the trial. The participant may also provide consent for Future Biomedical Research; however, the participant may participate in the main trial without participating in Future Biomedical Research. Other Inclusion Criteria Have intermediate-high risk, high risk RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status {Oza, 2022 #4431} Intermediate-high risk RCC pT2, Gr. 4 or sarcomatoid, N0, M0 pT3, Any Gr., N0, M0 High risk RCC pT4, Any Gr. N0, M0 pT Any stage, Any Gr., N+, M0 Have received no prior systemic therapy for advanced RCC unless having recently initiated immunotherapy with pembrolizumab for no more than 6 weeks or 1 dose prior to enrollment. Have undergone a partial nephroprotective or radical complete nephrectomy) Must have undergone a nephrectomy ≥28 days prior to signing informed consent and ≤12 weeks prior to enrollment. Must be tumor free as assessed by the investigator and validated by either CT or MRI scan of the brain and CAP ≤28 days from randomization. Have an ECOG PS ≤2. Have adequate organ function Exclusion Criteria: Medical Conditions Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. Has a known additional malignancy that is progressing or required active treatment ≤3 years ago. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy. Has an active infection requiring systemic therapy. Has a history of, or is currently on, dialysis. Has a known history of human immunodeficiency virus infection. No human immunodeficiency virus testing is required unless mandated by local health authority. Has a known active hepatitis B (hepatitis B surface antigen reactive) or HCV (eg, HCV RNA [qualitative] is detected). Has a known history of active tuberculosis (Bacillus tuberculosis). Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. Has a known psychiatric or substance abuse disorder that would interfere with the cooperation with the requirements of the trial in the opinion of the investigator. Has had a prior solid organ transplant. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients (refer to Investigator's Brochure for further details on excipients). A Woman of Childbearing Potential (WOCBP) who has a positive urine pregnancy test within 72 hours before randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Participants must be excluded/discontinued from the trial in the event of a positive or borderline positive test result. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the Screening visit through 120 days after the last dose of study treatment. Prior/Concomitant Therapy Has received prior anticancer therapy and not recovered from AEs due to previously administered agents. Note: denosumab may be allowed for bone protective purposes if dosing has been stable for ≥2 weeks before screening. Has received a live vaccine within 30 days prior to the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Prior/Concurrent Clinical Study Experience Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.