ACTIVE_NOT_RECRUITING

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

Conditions

Clear Cell Renal Cell Carcinoma Kidney Cancer Advanced Renal Cell Carcinoma Nivolumab 177Lu-girentuximab Memorial Sloan Kettering Cancer Center 21-328

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2022-02-16

Study Completion:2027-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05239533

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. 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 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 9. INR and aPTT ≤ 1.5 x ULN 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).	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).

Inclusion Criteria

Exclusion 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.
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
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
9. INR and aPTT ≤ 1.5 x ULN
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).

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).

Contacts and Locations

Principal Investigator

Darren Feldman, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester (Limited Protocol Activites)

Harrison, New York, 10604

United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau (Limited Protocol Activites)

Uniondale, New York, 11553

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Darren Feldman, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-02-16

Study Completion Date2027-03

Study Record Updates

Study Start Date2022-02-16

Study Completion Date2027-03

Terms related to this study

Keywords Provided by Researchers

Nivolumab
177Lu-girentuximab
Clear Cell Renal Cell Carcinoma
Kidney Cancer
Advanced Renal Cell Carcinoma
Memorial Sloan Kettering Cancer Center
21-328

Additional Relevant MeSH Terms

Clear Cell Renal Cell Carcinoma
Kidney Cancer
Advanced Renal Cell Carcinoma