NCT04626518

Who might be able to join this trial:

• You have been diagnosed with a specific type of kidney cancer called clear cell renal cell carcinoma (ccRCC) that has spread to nearby tissues or other parts of the body, confirmed by a tissue sample test.
• Your cancer got worse during or after treatment with a type of immunotherapy drug called a PD-(L)1 checkpoint inhibitor, you received at least 2 doses of it, and scans showed the cancer growing within 12 weeks of your last dose.
• Your cancer also got worse during or after treatment with a type of targeted therapy drug called a VEGF-TKI, confirmed by scans.
• You are able to swallow tablets or capsules by mouth.
• Your organs (such as kidneys, liver, and blood cells) are working well enough to meet the trial's requirements.
• If you are taking bone-strengthening medication, you must have started it at least 2 weeks before joining the trial.
• Any side effects from your previous cancer treatments have mostly cleared up (to a mild level or better).
• Your blood pressure is adequately controlled (at or below 150/90 mmHg) and has been stable on the same blood pressure medications for at least 1 week before joining.
• If you are male, you agree to abstain from sex with female partners or use contraception during treatment and for at least 7 days after your last dose of certain study drugs (confirm with trial site for full details based on which drugs apply to you).
• If you are female, you are not pregnant or breastfeeding, and either cannot become pregnant or agree to use contraception and avoid breastfeeding during the study and for a set period after your last dose of study drugs (the exact timeframe depends on which drugs you receive — confirm with trial site).

Who may not be able to join:

• You have a high level of protein in your urine (≥1g over 24 hours) and also have low blood oxygen levels, need extra oxygen, or have been coughing up blood in the last 3 weeks.
• You have had a significant heart or blood vessel problem in the past 12 months.
• You have had major surgery within the last 3 weeks.
• You have a history of serious lung disease.
• You have a history of inflammatory bowel disease (such as Crohn's disease or ulcerative colitis).
• You have or have had an abnormal connection (fistula) between organs, whether in the digestive system or elsewhere in the body.
• You have difficulty absorbing food or medication properly due to previous bowel surgery or digestive disease.
• You have previously been treated with both pembrolizumab and lenvatinib together at the same time.
• You have previously received a drug called belzutifan.
• You have had radiation therapy within the last 2 weeks.
• You have received a live vaccine (such as certain flu or other vaccines) within the last 30 days.
• You have received more than 4 previous systemic (whole-body) cancer treatments.
• You have a condition that weakens your immune system, or you have taken immune-suppressing medication within the last 7 days.
• You have another active or recently treated cancer (other than the kidney cancer being studied) within the past 3 years.
• Your kidney cancer has spread to your brain or the lining around your brain or spinal cord.
• You have an autoimmune disease (where your immune system attacks your own body) that has needed treatment in the past 2 years (hormone replacement therapy is generally still allowed — confirm with trial site).
• You currently have an active infection that requires medication.
• You have a known history of HIV infection.
• You have a known history of Hepatitis B.
• You have previously received an organ or tissue transplant from another person.

Important: Always verify eligibility with the trial site directly before applying.