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

Primary Purpose

Clear Cell Renal Cell Carcinoma, Kidney Cancer, Advanced Renal Cell Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
177Lu-labeled-girentuximab
Nivolumab
89Zr-girentuximab PET/CT
177Lu whole body (WB) planar and SPECT/CT scans
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clear Cell Renal Cell Carcinoma focused on measuring Nivolumab, 177Lu-girentuximab, Clear Cell Renal Cell Carcinoma, Kidney Cancer, Advanced Renal Cell Carcinoma, Memorial Sloan Kettering Cancer Center, 21-328

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Locally advanced unresectable or metastatic RCC with a component of clear cell histology 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. Lymphocyte count ≥ 500/μL
    4. Platelet count ≥100,000/μL (without transfusion within 2 weeks prior to Cycle

      1, Day 1; thrombopoietic agent use is allowed)

    5. 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).

Sites / Locations

  • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Westchester (Limited Protocol Activites)Recruiting
  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Nassau (Limited Protocol Activites)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Safety lead-in Phase: Participants with Advanced or Metastatic Clear Cell Renal Cell Carcinoma/RCC

Phase 2 Participants

Arm Description

Participants 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.

Participants 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.

Outcomes

Primary Outcome Measures

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)
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).

Secondary Outcome Measures

Full Information

First Posted
February 7, 2022
Last Updated
February 16, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT05239533
Brief Title
Study of Nivolumab in Combination With 177Lu-girentuximab for Kidney Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 16, 2022 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clear Cell Renal Cell Carcinoma, Kidney Cancer, Advanced Renal Cell Carcinoma
Keywords
Nivolumab, 177Lu-girentuximab, Clear Cell Renal Cell Carcinoma, Kidney Cancer, Advanced Renal Cell Carcinoma, Memorial Sloan Kettering Cancer Center, 21-328

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
3+3 design to establish the maximal tolerated dose (MTD)
Masking
None (Open Label)
Allocation
Randomized
Enrollment
29 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Safety lead-in Phase: Participants with Advanced or Metastatic Clear Cell Renal Cell Carcinoma/RCC
Arm Type
Experimental
Arm Description
Participants 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.
Arm Title
Phase 2 Participants
Arm Type
Experimental
Arm Description
Participants 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.
Intervention Type
Drug
Intervention Name(s)
177Lu-labeled-girentuximab
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Intervention Description
Nivolumab 240mg q2wk
Intervention Type
Diagnostic Test
Intervention Name(s)
89Zr-girentuximab PET/CT
Intervention Description
All patients will undergo a 89Zr-girentuximab PET/CT scan prior to every 177Lu-girentuximab administration
Intervention Type
Diagnostic Test
Intervention Name(s)
177Lu whole body (WB) planar and SPECT/CT scans
Intervention Description
177Lu whole body (WB) planar and SPECT/CT scans will be performed after each administration of 177Lu-girentuximab
Primary Outcome Measure Information:
Title
Maximal tolerated dose (MTD) of 177Lu-girentuximab
Description
To determine the maximal tolerated dose (MTD) of 177Lu-girentuximab when given in combination with nivolumab (safety lead-in)
Time Frame
24 (+/- 2) weeks
Title
Overall Response Rate/ORR
Description
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).
Time Frame
24 (+/- 2) weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Locally advanced unresectable or metastatic RCC with a component of clear cell histology 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 Adequate performance status and adequate organ function: ANC ≥ 1500 cells/μL WBC ≥ 2500/μL Lymphocyte count ≥ 500/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 a) Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled. 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. 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). Exclusion Criteria: 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. 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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Darren Feldman, MD
Phone
646-888-4740
Email
Feldmand@MSKCC.ORG
First Name & Middle Initial & Last Name or Official Title & Degree
Neeta Pandit-Taskar, MD
Phone
212-639-3046
Email
pandit-n@MSKCC.ORG
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Darren Feldman, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Darren Feldman, MD
Phone
646-888-4740
Facility Name
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Darren Feldman, MD
Phone
646-888-4740
Facility Name
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Darren Feldman, MD
Phone
646-888-4740
Facility Name
Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Darren Feldman, MD
Phone
646-888-4740
Facility Name
Memorial Sloan Kettering Westchester (Limited Protocol Activites)
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Darren Feldman, MD
Phone
646-888-4740
Facility Name
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Darren Feldman, MD
Phone
646-888-4740
Facility Name
Memorial Sloan Kettering Nassau (Limited Protocol Activites)
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Darren Feldman, MD
Phone
646-888-4740

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
Links:
URL
http://www.mskcc.org
Description
Memorial Sloan Kettering Cancer Center

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

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