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Combining nivolumab with 177Lu-girentuximab for advanced kidney cancer treatment

A Phase 2 Open-label Study of Nivolumab Combined With Lutetium 177-Labeled Anti-Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients With Clear Cell Advanced Renal Cell Carcinoma

Phase 2 Interventional Memorial Sloan Kettering Cancer Center · NCT05239533

This study is testing if combining two treatments, nivolumab and 177Lu-girentuximab, can help people with advanced kidney cancer feel better and improve their health after other treatments have not worked.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment41 (estimated)
Ages18 Years and up
SexAll
SponsorMemorial Sloan Kettering Cancer Center Academic / other
Drugs / interventionsgirentuximab, nivolumab, denosumab, prednisone
Locations7 sites (Basking Ridge, New Jersey and 6 other locations)
Trial IDNCT05239533 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and effectiveness of combining 177Lu-girentuximab with nivolumab for patients with advanced clear cell renal cell carcinoma (ccRCC) that expresses the CAIX protein. Participants will receive these treatments and undergo imaging scans to evaluate their response to therapy. The study aims to determine if this combination can improve outcomes for patients who have already received systemic therapy. Archival tumor tissue will be analyzed to confirm eligibility and assess the presence of CAIX expression.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced ccRCC that has not been surgically removed and has previously received systemic therapy.

Not a fit: Patients with early-stage kidney cancer or those who have not received prior systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a new effective option for patients with advanced kidney cancer.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy combinations, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Locally advanced unresectable or metastatic RCC with either a component of clear cell histology or carbonic anhydrase-IX (CAIX) expression by immunohistochemistry (IHC) i. Archival tumor tissue will be requested from patients who have undergone biopsy or tumor resection as part of routine clinical care prior to study participation to confirm diagnosis. Patients may undergo pre-treatment biopsy during the screening period if archival tissue is insufficient for baseline analysis.

   Tumor specimen may include nephrectomy or metastatic site specimen.
2. At least one evaluable metastatic lesion as defined by RECIST 1.1 on zirconium-89 (89Zr)-girentuximab PET/CT
3. At least one prior line of systemic therapy, including at least one prior treatment with anti PD-1 or PD-L1antibody
4. Age ≥18 years
5. KPS ≥ 70
6. Adequate performance status and adequate organ function:

   1. ANC ≥ 1500 cells/μL
   2. WBC ≥ 2500/μL
   3. Platelet count ≥100,000/μL (without transfusion within 2 weeks prior to Cycle

      1, Day 1; thrombopoietic agent use is allowed)
   4. Hemoglobin ≥9.0 g/dL (patients may be transfused or receive erythropoietic treatment to meet this criterion)
7. AST, ALT, and alkaline phosphatase ≤ 2.5 x ULN, with the following exceptions:

   1. Patients with documented liver metastases: AST and/or ALT ≤ 5 x ULN
   2. Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 x ULN
8. Serum bilirubin ≤ 2 x ULN

   a) Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled.
9. INR and aPTT ≤ 1.5 x ULN

   a) This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
10. Creatinine clearance ≥ 40mL/min, as measured by the Cockcroft-Gault formula.
11. Women of childbearing potential and men are advised to practice double-barrier contraception until a minimum of 6 months after IV 89Zr-girentuximab or177Lu-girentuximab administration. Women of childbearing potential are advised to practice double-barrier contraception until a minimum of 5 months after nivolumab.
12. Signed consent form by the participant or a legally authorized representative (LAR).

Exclusion Criteria:

1. Renal cell carcinoma with no histological evidence of any component of clear cell features. Note: Unclassified RCC with clear cell features is eligible for inclusion.
2. Prior treatment with 177Lu- girentuximab.
3. Known hypersensitivity to girentuximab or DFO (desferoxamine).
4. Exposure to murine or chimeric antibodies within the last 5 years.
5. Previous administration of any radionuclide within 10 half-lives of the same.
6. Radiotherapy for RCC within 14 days prior to Cycle 1, Day 1 except for single-fraction radiotherapy given for the indication of pain control which should be given at least 48 hours prior to C1D1.
7. Active untreated metastases to the brain \>1cm or symptomatic (of any size)
8. Active untreated metastases to the spinal cord or leptomeningeal disease
9. Patients with uncontrolled pain who are not on a stable pain regimen .
10. History of steroid requirement \> 10 mg daily prednisone in the past 2 years for autoimmune comorbidities.
11. Prior checkpoint inhibitor therapy discontinued due to immune related adverse events.
12. Anti-cancer therapy within 2 weeks prior to enrollment.
13. Uncontrolled hypercalcemia (≥ 1.5 mmol/L ionized calcium or Ca ≥ 12 mg/dL or corrected serum calcium ≥ ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.
14. Malignancies other than RCC within 3 years prior to Cycle 1, Day 1, except for those with a negligible risk of metastasis or death, treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent, non-muscle-invasive urothelial carcinoma).
15. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
16. HIV infection if not well-controlled with antiretroviral therapy
17. Patients with active or chronic hepatitis B or hepatitis C infection.
18. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, unstable angina, or EF \< 50%.
19. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
20. History of stroke or transient ischemic attack within 6 months prior to Cycle 1, Day 1.
21. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Cycle 1, Day 1.
22. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
23. Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding .
24. Evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
25. Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture.
26. Major surgery within 4 weeks prior to enrollment (biopsy or line placement can be performed up to 24 hours prior to enrollment).
27. Pregnant and lactating women.
28. Patients in whom nivolumab treatment is not feasible for any reason (including financial/insurance).

Where this trial is running

Basking Ridge, New Jersey and 6 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Clear Cell Renal Cell CarcinomaKidney CancerAdvanced Renal Cell CarcinomaNivolumab177Lu-girentuximabMemorial Sloan Kettering Cancer Center21-328
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.