Testing the Investigational Medication Pembrolizumab After Kidney Removal for Patients With Non-Clear Cell Renal Cell Carcinoma

NCT07689240 | Not Yet Recruiting Phase 3 FDA Drug

• 3 other identifiers: NCI-2026-04730EA8252U10CA180820
• Study Type: interventional
• Target: 400
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase III trial compares the effect of pembrolizumab to active surveillance after a surgical procedure to completely or partially remove a kidney (nephrectomy) in improving time without disease in patients with non-clear cell renal cell cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab after nephrectomy may be more effective than the usual active surveillance approach for improving time without disease in patients with non-clear cell renal cell cancer.

Conditions

Stage III Renal Cell Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8; Non-Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Disease-free survival (DFS)

  A superiority test of DFS for pembrolizumab arm versus (vs.) active surveillance arm will be performed at one-sided 0.025 significance level, using a stratified log-rank test assuming exponential failure.

  From randomization to first documented local recurrence, distant metastasis, secondary systemic malignancy, or death due to any cause, whichever occurs first, assessed up to 10 years

Secondary Outcomes (9)

• Overall survival (OS)

  From randomization to death from any cause, assessed up to 10 years

• Incidence of adverse events

  Up to 1 year

• DFS among those that are circulating tumor deoxyribonucleic acid (ctDNA) positive

  Up to 10 years

• OS among those that are ctDNA positive

  Up to 10 years

• ctDNA clearance rate prediction

  At week 12

Other Outcomes (3)

• DFS by sex

  Up to 10 years

• DFS by race

  Up to 10 years

• DFS by ethnicity

  Up to 10 years

Study Arms (2)

Arm A (active surveillance)

ACTIVE COMPARATOR

Patients undergo active surveillance, including CT or MRI, every 3 months for 1 year. Patients also undergo collection of blood samples on study and CT or MRI during follow up. Patients may undergo ECHO and/or bone scan and/or PET/CT if clinically indicated.

Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Other: Patient Observation; Procedure: Positron Emission Tomography

Arm B (pembrolizumab)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout the trial and collection of blood samples on study. Patients may undergo ECHO and/or bone scan and/or PET/CT if clinically indicated.

Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab; Procedure: Positron Emission Tomography

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm A (active surveillance); Arm B (pembrolizumab)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Arm A (active surveillance); Arm B (pembrolizumab)

Computed Tomography PROCEDURE

Undergo CT and PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm A (active surveillance); Arm B (pembrolizumab)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Arm A (active surveillance); Arm B (pembrolizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm A (active surveillance); Arm B (pembrolizumab)

Patient Observation OTHER

Undergo active surveillance

Also known as: Active Surveillance, deferred therapy, expectant management, Observation, Watchful Waiting

Arm A (active surveillance)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, Pembrolizumab Biosimilar RPH-075, Pembrolizumab Biosimilar SB27, QL2107, RPH 075, RPH-075, RPH075, SB 27, SB-27, SB27, SCH 900475, SCH-900475, SCH900475

Arm B (pembrolizumab)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Arm A (active surveillance); Arm B (pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be ≥ 18 years of age
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Patient must have histologically confirmed non-clear cell renal cell carcinoma (nccRCC) with ≥ pT3Nx or pTanyN+ or pTanyNanyM1 with no evidence of disease (NED) per the American Joint Committee on Cancer (AJCC) 8th edition
• Patient must not have renal medullary carcinoma
• Patient must have had a partial or radical nephrectomy. In the case of patients with M1 NED status, a complete resection of the metastatic lesion(s) (metastasectomy) must have been completed at the time of nephrectomy or within 1 year after nephrectomy
• Positive margins are allowed as long as no gross disease
• Patient must not have residual thrombus post nephrectomy in the vena renalis or vena cava
• Patient must be randomized ≤ 16 weeks after nephrectomy and/or \< 16 weeks after metastasectomy
• Patient must have undergone imaging of chest, abdomen and pelvis with a CT or MRI after nephrectomy/metastasectomy and within 42 days prior to randomization documenting there is no evidence of liver, bone, or brain metastases
• Patient must not have received any prior anti-PD-1/PD-L1 or CTLA-4 agents
• Patient must not have received any prior radiotherapy for nccRCC
• Patient must not have received prior systemic treatment for nccRCC (except nephrectomy or metastasectomy). Patient must not have received prior immune checkpoint inhibitor agents for other cancers within 2 years prior to randomization
• Patient must not have active known or suspected autoimmune disease requiring systemic immunosuppression. The following autoimmune disorders are permitted: patients with vitiligo, type I diabetes mellitus, controlled/stable hypo or hyperthyroidism due to autoimmune or non-autoimmune conditions (hormone replacement is allowed), psoriasis not requiring systemic treatment
• Patient must not be on any immunosuppressant therapy other than inhaled steroids, intranasal steroids, topical steroids, injection steroids and systemic steroids up to 10mg prednisone equivalent
• Patient must have recovered adequately from toxicity and/or complications related to any surgery received prior to randomization

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Specimen Handling; Magnetic Resonance Spectroscopy; Watchful Waiting; Observation; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Methods

Study Officials

• Mehmet A Bilen

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2026
• First Posted: July 8, 2026
• Study Start (Estimated): February 10, 2027
• Primary Completion (Estimated): January 1, 2032
• Study Completion (Estimated): January 1, 2032
• Last Updated: July 8, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share