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Clear Cell Renal Cell CarcinomaPhase 2NCT05239533

Study of Nivolumab in Combination With 177Lu-girentuximab for Kidney Cancer

A Phase 2 study testing 177Lu-labeled-girentuximab, Nivolumab and 89Zr-girentuximab PET/CT in people with Clear Cell Renal Cell Carcinoma and Kidney Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this study is to see if the combination of 177Lu-girentuximab and nivolumab is a safe and effective treatment for advanced clear cell renal cell carcinoma/ccRCC that has the CAIX protein. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
177Lu-labeled-girentuximab, Nivolumab and 89Zr-girentuximab PET/CT
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
7 sitesUnited States
Study dates
16 Feb 2022to Mar 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • At least one evaluable metastatic lesion as defined by RECIST 1.1 on zirconium-89 (89Zr)-girentuximab PET/CT
  • At least one prior line of systemic therapy, including at least one prior treatment with anti PD-1 or PD-L1antibody
  • Age ≥18 years
  • KPS ≥ 70
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  • Adequate performance status and adequate organ function:
  • ANC ≥ 1500 cells/μL
  • WBC ≥ 2500/μL
  • Platelet count ≥100,000/μL (without transfusion within 2 weeks prior to Cycle
  • 1, Day 1; thrombopoietic agent use is allowed)
  • Hemoglobin ≥9.0 g/dL (patients may be transfused or receive erythropoietic treatment to meet this criterion)
  • AST, ALT, and alkaline phosphatase ≤ 2.5 x ULN, with the following exceptions:
  • Patients with documented liver metastases: AST and/or ALT ≤ 5 x ULN
  • Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 x ULN
  • Serum bilirubin ≤ 2 x ULN
  • Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled.
  • INR and aPTT ≤ 1.5 x ULN
  • This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
  • Creatinine clearance ≥ 40mL/min, as measured by the Cockcroft-Gault formula.
  • 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.
  • Signed consent form by the participant or a legally authorized representative (LAR).

Who cannot join

  • 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.
  • Prior treatment with 177Lu- girentuximab.
  • Known hypersensitivity to girentuximab or DFO (desferoxamine).
  • Exposure to murine or chimeric antibodies within the last 5 years.
  • Previous administration of any radionuclide within 10 half-lives of the same.
  • 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.
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  • Active untreated metastases to the brain >1cm or symptomatic (of any size)
  • Active untreated metastases to the spinal cord or leptomeningeal disease
  • Patients with uncontrolled pain who are not on a stable pain regimen .
  • History of steroid requirement > 10 mg daily prednisone in the past 2 years for autoimmune comorbidities.
  • Prior checkpoint inhibitor therapy discontinued due to immune related adverse events.
  • Anti-cancer therapy within 2 weeks prior to enrollment.
  • 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.
  • 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).
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  • HIV infection if not well-controlled with antiretroviral therapy
  • Patients with active or chronic hepatitis B or hepatitis C infection.
  • 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%.
  • 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.
  • History of stroke or transient ischemic attack within 6 months prior to Cycle 1, Day 1.
  • Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Cycle 1, Day 1.
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
  • Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding .
  • Evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
  • Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture.
  • Major surgery within 4 weeks prior to enrollment (biopsy or line placement can be performed up to 24 hours prior to enrollment).
  • Pregnant and lactating women.
  • Patients in whom nivolumab treatment is not feasible for any reason (including financial/insurance).

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester (Limited Protocol Activites)

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)

    New York, New York, 10065

  • Memorial Sloan Kettering Nassau (Limited Protocol Activites)

    Uniondale, New York, 11553

Other trials in United States

About this study

Official title: 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

The purpose of this study is to see if the combination of 177Lu-girentuximab and nivolumab is a safe and effective treatment for advanced clear cell renal cell carcinoma/ccRCC that has the CAIX protein.

Being tested
177Lu-labeled-girentuximab, Nivolumab, 89Zr-girentuximab PET/CT, 177Lu whole body (WB) planar and SPECT/CT scans
Keywords
Nivolumab, 177Lu-girentuximab, Clear Cell Renal Cell Carcinoma, Kidney Cancer, Advanced Renal Cell Carcinoma, Memorial Sloan Kettering Cancer Center, 21-328
Medical subject headings
Carcinoma, Renal Cell, Kidney Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 177Lu-labeled-girentuximabDrug

    The initial starting dose/Dose Level 1 of 177Lu-labeled-girentuximab is 1804 MBq/m2. if 0/3 or 1/6 DLTs, participants will be treated at Dose Level 2 177Lu-girentuximab 2405 MBq/m2. >/= 2/6 DLTs, Dose Level -1 is 177Lu-girentuximab 1353 MBq/m2

    Once the MTD is established, a Simon two-stage optimal design will commence.

  • NivolumabDrug

    Nivolumab 240mg q2wk

  • 89Zr-girentuximab PET/CTDiagnostic test

    All patients will undergo a 89Zr-girentuximab PET/CT scan prior to every 177Lu-girentuximab administration

  • 177Lu whole body (WB) planar and SPECT/CT scansDiagnostic test

    177Lu whole body (WB) planar and SPECT/CT scans will be performed after each administration of 177Lu-girentuximab

Study groups in NCT05239533
Study groupRoleWhat they receive
Safety lead-in Phase: Participants with Advanced or Metastatic Clear Cell Renal Cell Carcinoma/RCCExperimentalParticipants have Advanced or Metastatic Clear Cell Renal Cell Carcinoma/RCC. The protocol will start with a safety-lead in phase using a 3+3 design to establish the maximal tolerated dose (MTD) of 177Lu-labeled-girentuximab in combination with standard-dose nivolumab. The initial starting dose of 177Lu-labeled-girentuximab is 1804 MBq/m2 which is 75% of the single agent dose established in prior studies and will proceed as shown in the schema below. Once the MTD is established, a Simon two-stage optimal design will commence. 10 patients will be enrolled in the first stage and if no responses are observed, the study will be terminated. If 1 or more responses are observed in the first 10 patients, we will extend enrollment to a total of 29 patients (19 additional patients) in the second stage.
Receives: Drug: 177Lu-labeled-girentuximab; Drug: Nivolumab; Diagnostic Test: 89Zr-girentuximab PET/CT; Diagnostic Test: 177Lu whole body (WB) planar and SPECT/CT scans
Phase 2 ParticipantsExperimentalParticipants have Advanced or Metastatic Clear Cell Renal Cell Carcinoma/RCC. If 1 or more responses are observed in the first 10 patients, we will extend enrollment to a total of 29 patients (19 additional patients) in the second stage.
Receives: Drug: 177Lu-labeled-girentuximab; Drug: Nivolumab; Diagnostic Test: 89Zr-girentuximab PET/CT; Diagnostic Test: 177Lu whole body (WB) planar and SPECT/CT scans

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximal tolerated dose (MTD) of 177Lu-girentuximab

    To determine the maximal tolerated dose (MTD) of 177Lu-girentuximab when given in combination with nivolumab (safety lead-in)

    Measured: 24 (+/- 2) weeks

  2. Overall Response Rate/ORR

    efficacy of the combination at the MTD of 177Lu-labelled girentuximab in patients with advanced ccRCC as assessed by best ORR by 24 (+/- 2) weeks by Response Evaluation Criteria In Solid Tumors (RECIST v1.1).

    Measured: 24 (+/- 2) weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2022
  2. Study start16 Feb 2022
  3. Primary completionMar 2027 (estimated)
  4. Study completionMar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
3+3 design to establish the maximal tolerated dose (MTD)
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05239533
Sponsor's protocol ID
21-328
Status last verified
Jan 2026
First submitted
7 Feb 2022
Last updated
14 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 177Lu-labeled-girentuximab, Nivolumab and 89Zr-girentuximab PET/CT in people with Clear Cell Renal Cell Carcinoma and Kidney Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximal tolerated dose (MTD) of 177Lu-girentuximab (time frame: 24 (+/- 2) weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05239533.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2026.

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