NCT05239533

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
9

participants targeted

Target at below P25 for phase_2

Timeline
10mo left

Started Feb 2022

Longer than P75 for phase_2

Geographic Reach
1 country

7 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress84%
Feb 2022Mar 2027

First Submitted

Initial submission to the registry

February 7, 2022

Completed
8 days until next milestone

First Posted

Study publicly available on registry

February 15, 2022

Completed
1 day until next milestone

Study Start

First participant enrolled

February 16, 2022

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2027

Last Updated

January 14, 2026

Status Verified

January 1, 2026

Enrollment Period

5 years

First QC Date

February 7, 2022

Last Update Submit

January 12, 2026

Conditions

Clear Cell Renal Cell CarcinomaKidney CancerAdvanced Renal Cell Carcinoma

Keywords

Nivolumab177Lu-girentuximabClear Cell Renal Cell CarcinomaKidney CancerAdvanced Renal Cell CarcinomaMemorial Sloan Kettering Cancer Center21-328

Outcome Measures

Primary Outcomes (2)

  • 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)

    24 (+/- 2) weeks

  • 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).

    24 (+/- 2) weeks

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: 177Lu-labeled-girentuximabDrug: NivolumabDiagnostic Test: 89Zr-girentuximab PET/CTDiagnostic Test: 177Lu whole body (WB) planar and SPECT/CT scans

Phase 2 Participants

EXPERIMENTAL

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.

Drug: 177Lu-labeled-girentuximabDrug: NivolumabDiagnostic Test: 89Zr-girentuximab PET/CTDiagnostic Test: 177Lu whole body (WB) planar and SPECT/CT scans

Interventions

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.

Phase 2 ParticipantsSafety lead-in Phase: Participants with Advanced or Metastatic Clear Cell Renal Cell Carcinoma/RCC
NivolumabDRUG

Nivolumab 240mg q2wk

Phase 2 ParticipantsSafety lead-in Phase: Participants with Advanced or Metastatic Clear Cell Renal Cell Carcinoma/RCC
89Zr-girentuximab PET/CTDIAGNOSTIC_TEST

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

Phase 2 ParticipantsSafety lead-in Phase: Participants with Advanced or Metastatic Clear Cell Renal Cell Carcinoma/RCC
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

Phase 2 ParticipantsSafety lead-in Phase: Participants with Advanced or Metastatic Clear Cell Renal Cell Carcinoma/RCC

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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
  • , 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
  • +7 more criteria

You may not qualify if:

  • 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
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activites)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activites)

Uniondale, New York, 11553, United States

Location

Related Links

MeSH Terms

Conditions

Carcinoma, Renal CellKidney Neoplasms

Interventions

NivolumabSingle Photon Emission Computed Tomography Computed Tomography

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsTomography, Emission-Computed, Single-PhotonTomography, Emission-ComputedImage Interpretation, Computer-AssistedDiagnostic ImagingDiagnostic Techniques and ProceduresDiagnosisTomography, X-Ray ComputedMultimodal ImagingRadiographic Image EnhancementImage EnhancementPhotographyRadiographyTomography, X-RayRadionuclide ImagingTomographyDiagnostic Techniques, Radioisotope

Study Officials

  • Darren Feldman, MD

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: 3+3 design to establish the maximal tolerated dose (MTD)
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 7, 2022

First Posted

February 15, 2022

Study Start

February 16, 2022

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

March 1, 2027

Last Updated

January 14, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will share

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.

Locations

US(7)