A Multicenter, Double-blind, Randomized Phase 3 Study to Compare the Efficacy and Safety of Belzutifan (MK-6482) Plus Pembrolizumab (MK-3475)

This trial is testing belzutifan (MK-6482) plus pembrolizumab (pembro) in people who have had surgery for a type of kidney cancer called clear cell renal cell carcinoma (ccRCC).The purpose of this trial is to:

• Test the safety of the trial drug, belzutifan plus pembro, compared to placebo plus pembro
• See how well belzutifan plus pembro works, compared to placebo plus pembro
• See if participants who get belzutifan plus pembro have a better quality of life, compared to those who get placebo plus pembro

Belzutifan is an experimental drug. It has been approved by some health authorities for treating some types of cancer, including renal cell carcinoma in people with a rare disease called Von Hippel Lindau disease.

Pembro is an experimental treatment. It has been approved by some health authorities for treating various cancers, including renal cell carcinoma. This trial will compare belzutifan plus pembro to placebo plus pembro. A placebo looks like a trial drug, but it has no active ingredients.

Inova Schar Cancer Institute
8081 Innovation Park Dr.
Fairfax, VA 22031

A department of Inova Fairfax Hospital

• Adults 18 years of age or older
• A histologically or cytologically confirmed diagnosis of RCC with clear cell component per AJCC (8th Edition), with or without sarcomatoid features.
• Intermediate-high risk, high risk, or M1 NED RCC as defined by the following pathological tumor-node metastasis and tumor grading:
  • Intermediate-high risk RCC:
    - pT2, Grade 4 or sarcomatoid, N0, M0
    - pT3, any grade, N0, M0
  • High-risk RCC:
    - pT4, any grade, N0, M0
    - pT, any stage, any grade, N+, M0
  • M1 NED RCC participants who present not only with the primary kidney tumor, but also solid, isolated, soft tissue metastases that can be completely resected at 1 of the following:
    - the time of nephrectomy (synchronous), or ≤2 years from nephrectomy (metachronous)
• Has undergone complete resection of the primary tumor (partial or radical nephrectomy) and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants.
  • Note: Participants with microscopically positive soft tissue or vascular margins without gross residual disease are permitted.
• Must have undergone a nephrectomy and/or metastasectomy ≤12 weeks prior to randomization.
• Must be tumor-free before randomization as assessed by the investigator and verified by BICR by either CT or MRI scan of the brain and CAP (≤28 days from randomization) and a bone scan (≤42 days from randomization).
• Must have provided tissue per any of the following:
  • Nephrectomy only: tissue from nephrectomy (required).
  • Synchronous M1 NED: tissue from nephrectomy (required) and tissue from metastasectomy (if available).
  • Metachronous M1 NED: tissue from metastasectomy (required) and tissue from nephrectomy (if available).
    - Note: FFPE tissue blocks are preferred to slides.
• Has ECOG performance status of 0 to 1 within 10 days before randomization.
• Additional eligibility in protocol

• Pregnancy/breastfeeding
• Has had a major surgery, other than nephrectomy plus resection of preexisting metastases for M1 NED participants, within 4 weeks prior to randomization.
  • Note: If participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study intervention.
• Residual thrombus post nephrectomy in the vena renalis or vena cava.
• Has any of the following:
  • Pulse oximeter reading <92% at rest, or
  • Requires intermittent supplemental oxygen, or
  • Requires chronic supplemental oxygen.
• Clinically significant cardiovascular disease within 6 months from first dose of study intervention, including NYHA III or IV congestive heart failure, unstable angina, myocardial infarction, cerebrovascular accident, undergone CABG or PTCA, or cardiac arrhythmia.
  • Note: Medically controlled arrhythmia stable on medication is permitted.
• Other clinically significant disorders such as:
  • Serious active nonhealing wound/ulcer/bone fracture
  • Requirement for hemodialysis or peritoneal dialysis
• Preexisting brain or bone metastatic lesions.
• Has received colony-stimulating factors (eg, G-CSF, GM-CSF) or recombinant EPO or transfusion within 28 days before study intervention initiation.
• Is unable to swallow orally administered medication or has a history or current evidence of a GI condition (eg, inflammatory bowel disease, Crohn’s disease, ulcerative colitis) or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral study intervention.
• Has a severe hypersensitivity (Grade ≥3) reaction to belzutifan/placebo or pembrolizumab and/or any of their excipients.
• Received prior systemic therapy for RCC
• Received prior radiotherapy for RCC.
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
• Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
  • Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• 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 intervention.
• A known additional malignancy (other than RCC treated with nephrectomy and/or metastasectomy) that is progressing or has required active treatment within the past 3 years.
  • Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
• 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.
• A history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• A known history of HIV infection, a known history of Hepatitis B (defined as HbsAg reactive), or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
  • Note: No testing for HIV, hepatitis B, and hepatitis C is required unless mandated by local health authority.
• An allogenic tissue/solid organ transplant.
• Additional ineligibility in protocol

For more information, go to: https://clinicaltrials.gov/ct2/show/NCT05239728