Belzutifan plus zanzalintinib versus cabozantinib for recurrent advanced kidney cancer after adjuvant PD-1/L1 therapy

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a randomized Phase 3 trial comparing the combination of belzutifan and zanzalintinib to cabozantinib in patients with recurrent advanced renal cell carcinoma after prior adjuvant PD-1/L1 therapy. Eligible participants have unresectable Stage IV disease with a clear cell component, measurable disease by RECIST 1.1, and recurrence during or within 24 months after adjuvant PD-1/L1, with no other prior systemic RCC therapy allowed. The primary outcomes include overall survival and progression-free survival, with patients followed by regular imaging and clinical assessments. Study sites for enrollment are located in Buenos Aires, Argentina.

Why it matters

Who can join: the full rules

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Has a histologically confirmed diagnosis of unresectable, advanced renal cell cancer (RCC) with clear cell component (with or without sarcomatoid features) i.e., Stage IV renal cell cancer per American Joint Committee on Cancer (AJCC) (8th Edition)
* Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
* Has disease recurrence during adjuvant anti-programmed cell death 1/programmed cell death ligand 1 (PD-1/L1) therapy or recurrence ≤24 months following the last dose of adjuvant anti-PD-1/L1 therapy
* Has received no other prior systemic therapy for their RCC except for their adjuvant anti-PD-1/L1 therapy

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, new-onset angina, pulmonary embolism, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
* Had deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization
* Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram
* Has had major surgery within 8 weeks before randomization or has not adequately recovered from major surgery or has ongoing surgical complications
* Has current pneumonitis/interstitial lung disease
* Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain), ascites, or pericardial fluid requiring drainage within 4 weeks prior to randomization
* Has a gastrointestinal disorder including those associated with a high risk of perforation or fistula formation
* Has a serious active nonhealing wound/ulcer/bone fracture
* Has a requirement for hemodialysis or peritoneal dialysis
* Has history of human immunodeficiency virus infection
* Has hepatitis B or hepatitis C virus
* Has pharmacologically uncompensated, symptomatic hypothyroidism
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention

Where it's running

• Alaska Oncology and Hematology ( Site 0133)
  Anchorage, Alaska, United States Recruiting
• Providence Medical Foundation ( Site 0141)
  Fullerton, California, United States Recruiting
• USC Norris Comprehensive Cancer Center ( Site 0126)
  Los Angeles, California, United States Recruiting
• Cedars-Sinai Medical Center ( Site 0112)
  Los Angeles, California, United States Recruiting
• New England Cancer Specialists ( Site 0132)
  Westbrook, Maine, United States Recruiting
• Greater Baltimore Medical Center ( Site 0145)
  Baltimore, Maryland, United States Recruiting

+77 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Toll Free Number
• Email: Trialsites@msd.com
• Phone: 1-888-577-8839

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.