The following clinical trials represent a selection of key studies currently recruiting patients with renal-cell carcinoma for inclusion in investigations of new therapies and new regimens of existing treatments for the disease. Each clinical trial description includes the NLM Identifier to be used as a reference with ClinicalTrials.gov. This information can help oncology practice managers and providers direct eligible patients to one of these clinical trials.
1 Nivolumab plus Ipilimumab versus Nivolumab Alone for Prevention of Recurrence After Partial or Radical Nephrectomy
The purpose of this randomized, double-blind, phase 3 study is to determine the safety and efficacy of nivolumab (Opdivo) plus ipilimumab (Yervoy) versus nivolumab alone in delaying or preventing disease recurrence in patients who have had a partial or radical nephrectomy who are at high risk for disease recurrence. Patients aged ≥18 years who have had complete resection of a kidney tumor with negative surgical margins obtained, whose postnephrectomy tumor shows renal-cell carcinoma (RCC) with a predominantly clear-cell histology, who have an Eastern Cooperative Oncology Group performance status 0 to 1, and who have no distant metastases or macroscopic residual disease after nephrectomy may be eligible if other criteria are met. Eligible participants will be randomized to receive either nivolumab plus ipilimumab, nivolumab plus placebo, or placebo for both.
The primary outcome measure is disease-free survival as assessed by blinded independent central review. The secondary outcome measures include overall survival (OS), incidence of adverse events (AEs), and disease-free survival. The study plans to enroll 1600 participants throughout the United States and worldwide. For more information, contact the recruiting sites directly. If there is no contact information, e-mail
2 Belzutifan versus Everolimus for Advanced RCC
The purpose of this randomized, open-label, phase 3 study is to evaluate and compare the efficacy of belzutifan (Welireg) plus everolimus (Disperz) with respect to progression-free survival (PFS) and OS in patients with advanced RCC who have had disease progression after receiving previous PD-1/PD-L1 and VEGF-targeted therapies. Patients aged ≥18 years who have unresectable, locally advanced, or metastatic clear-cell RCC, who have received no more than 3 previous systemic regimens, and who have had disease progression after systemic treatment may be eligible if other criteria are met. Eligible participants will be randomized to receive either 120 mg of belzutifan orally (PO) once daily or 10 mg of everolimus PO once daily.
The primary outcome measures are PFS per RECIST version 1.1, defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever comes first, and OS. Secondary outcome measures include objective response rate (ORR); duration of response (DOR); number of participants who have ≥1 AEs; number of participants discontinuing study treatment due to any AE; time to deterioration in health-related quality of life, physical functioning, and disease symptoms; and changes from baseline in health-related quality of life, physical functioning, and disease symptoms. The study plans to enroll 736 participants throughout the United States and worldwide. For more information, contact Merck Sharp & Dohme Corp at 1-888-577-8839 or
3 Pembrolizumab plus Belzutifan plus Lenvatinib or Pembrolizumab/Quavonlimab plus Lenvatinib versus Pembrolizumab plus Lenvatinib for Advanced Clear-Cell RCC
The purpose of this randomized, open-label, phase 3 study is to evaluate the efficacy and safety of pembrolizumab (Keytruda) plus belzutifan (Welireg) plus lenvatinib (Lenvima) or pembrolizumab/quavonlimab (MK-1308A) plus lenvatinib versus pembrolizumab plus lenvatinib in the treatment of patients with advanced clear-cell RCC. Patients aged ≥18 years with a histologically confirmed diagnosis of clear-cell RCC, who have not received previous systemic therapy for advanced disease, and who have adequately controlled blood pressure with or without antihypertensive medications may be eligible if other criteria are met. Eligible patients will be randomized to receive pembrolizumab 400 mg intravenously (IV) every 6 weeks plus belzutifan 120 mg PO daily plus lenvatinib 20 mg PO daily; pembrolizumab/quavonlimab combination IV every 6 weeks plus lenvatinib 20 mg PO daily; or pembrolizumab 400 mg IV every 6 weeks plus lenvatinib 20 mg PO daily.
The primary outcome measures are PFS and OS, from the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Secondary outcome measures include ORR, DOR, number of participants who have ≥1 AEs, and the number of participants who discontinue study treatment due to any AE. The study plans to enroll 1431 participants throughout the United States and worldwide. For more information, contact Merck Sharp & Dohme Corp at 1-888-577-8839 or
4 Atezolizumab plus Cabozantinib versus Cabozantinib Alone for Advanced RCC
The purpose of this randomized, open-label, multicenter, phase 3 study is to evaluate the efficacy and safety of the atezolizumab (Tecentriq) and cabozantinib (Cabometyx) combination versus cabozantinib monotherapy in patients with inoperable, locally advanced, or metastatic RCC who had disease progression during or after immune checkpoint inhibitor treatment. Patients aged ≥18 years with histologically confirmed locally advanced or metastatic clear-cell or non–clear-cell RCC, who have radiographic disease progression during or after treatment with an immune checkpoint inhibitor in the first- or second-line treatment setting, who have a Karnofsky performance status score of ≥70, and who have measurable disease per RECIST version 1.1 may be eligible if other criteria are met. Eligible participants will be randomized to receive atezolizumab 1200 mg IV on day 1 of each 21-day cycle every 3 weeks plus cabozantinib 60 mg PO daily, or cabozantinib 60 mg PO daily.
The primary outcome measures include PFS and OS from the time from randomization to death from any cause. Secondary outcome measures include PFS, ORR, and DOR; number of participants with AEs; concentrations of atezolizumab and cabozantinib; and the prevalence and incidence of antidrug antibodies to atezolizumab. The study plans to enroll 500 participants throughout the United States and worldwide. For more information, contact Hoffmann-La Roche at 1-888-662-6728, or e-mail
5 Pazopanib with or without Abexinostat for Locally Advanced or Metastatic RCC
The purpose of this randomized, double-blind, placebo-controlled, phase 3 study is to evaluate the safety and efficacy of pazopanib (Votrient) with or without abexinostat (PCI-24781) in the treatment of patients with locally advanced, unresectable, or metastatic RCC. Patients aged ≥18 years with histologically confirmed clear-cell RCC that is measurable as per RECIST version 1.1, who have not had any previous VEGF tyrosine kinase inhibitor treatment in either the neoadjuvant or locally advanced or metastatic setting, who have an Eastern Cooperative Oncology Group performance status of 0 or 1, and who are at least 2 weeks from last systemic treatment or dose of radiation before date of randomization may be eligible if other criteria are met. Eligible participants will be randomized to receive pazopanib 800 mg PO daily on days 1-28 of each treatment cycle plus abexinostat 80 mg PO twice daily on days 1-4, 8-11, and 15-18 of each 28-day cycle in 2 doses 4 hours apart, or pazopanib plus placebo.
The primary outcome measure is PFS from randomization date to date of first documentation of disease progression or death. Secondary outcome measures include PFS, OS, ORR, DOR, AEs by National Cancer Institute’s Common Terminology Criteria for Adverse Events version 5, and mean changes from baseline in Functional Assessment of Cancer Therapy Kidney System Index scores and Functional Assessment of Chronic Illness Therapy scores. The study plans to enroll 413 participants throughout the United States and worldwide. For more information, contact Sophia Paspal, PhD, at 1-610-405-5974 or
6 Nivolumab plus Ipilimumab Followed by Nivolumab Alone versus Cabozantinib plus Nivolumab for Metastatic Untreated RCC
The purpose of this randomized, parallel, phase 3 study is to compare the standard treatment of ipilimumab (Yervoy) plus nivolumab (Opdivo) followed by nivolumab versus ipilimumab plus nivolumab followed by nivolumab plus cabozantinib (Cabometyx) in patients with metastatic, untreated RCC. Patients aged ≥18 years with histologically confirmed and metastatic clear-cell RCC; a Karnofsky performance status ≥70%; who have not received previous treatment with a PD-1, PD-L1, or CTLA-4 agent; who have had successful completion of ≥1 cycles of ipilimumab plus nivolumab within 70 days of randomization; and who have not had cancer therapy less than 28 days before registration may be eligible if other criteria are met. Eligible participants will be randomized to receive induction treatment with ipilimumab plus nivolumab IV over 30 minutes every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity, followed by either nivolumab IV over 30 minutes on day 1 every 28 days or cabozantinib PO on days 1-28 plus nivolumab IV on day 1 every 28 days.
The primary outcome measure is OS from registration date to death from any cause, assessed up to 5 years. Secondary outcome measures include PFS, complete response, ORR, incidence of AEs, and proportion of participants who discontinue treatment before 1 year from date of study registration. The study plans to enroll 1046 participants throughout the United States and worldwide. For more information, contact the trial sites directly. The NLM identifier is NCT03793166.