Belzutifan treatment with PET imaging of CAIX in metastatic clear cell kidney cancer

A Phase 1b Study to Assess the Effects of Belzutifan on 89Zr-DFO-girentuximab Uptake as a Surrogate to Determine CAIX Tumor Expression in Patients With Clear Cell Renal Cell Carcinoma

This study will test whether belzutifan changes CAIX levels on 89Zr-DFO-girentuximab PET scans in adults with metastatic clear cell kidney cancer who progressed after immunotherapy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: NYU Langone Health (Academic / other)
• Drugs / interventions: girentuximab
• Locations: 1 site (New York, New York)
• Trial ID: NCT07179770 on ClinicalTrials.gov

What this trial studies

This Phase 1 study gives adults with metastatic clear cell renal cell carcinoma belzutifan as a single agent and uses 89Zr-DFO-girentuximab PET scans to image CAIX expression before and four weeks after starting treatment. Eligible participants have measurable disease and radiographic progression after prior immune checkpoint inhibitor therapy. The protocol measures changes in PET uptake to determine whether HIF-2α inhibition by belzutifan alters tumor CAIX levels. Results will inform development of combinations with CAIX-targeted agents, including potential radioimmunotherapy approaches.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed metastatic clear cell RCC, measurable disease, KPS ≥60%, adequate organ function, and radiographic progression after immune checkpoint inhibitor therapy are ideal candidates.

Not a fit: Patients whose tumors lack CAIX expression, who cannot undergo PET imaging, or who have poor organ or marrow function may not benefit from this study.

Why it matters

Potential benefit: If successful, the imaging results could identify patients likely to benefit from combining belzutifan with CAIX-targeted treatments and guide development of targeted radioimmunotherapy.

How similar studies have performed: Belzutifan has shown clinical activity in RCC and 89Zr-girentuximab PET is an established CAIX imaging method, but using PET to measure belzutifan-induced changes in CAIX is novel.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed advanced clear cell RCC
2. Radiographic disease progression to prior immune checkpoint inhibitor (ICI) therapy for RCC

   * ICI for adjuvant therapy: Patients who experienced radiographic tumor progression during or within 6 months after last dose of adjuvant ICI
   * ICI for locally advanced or metastatic disease: radiographic disease progression during or following ICI treatment in the 1st line setting
   * Minimum two previous treatment regimens but no maximum limit
3. Measurable disease per RECIST v1.1
4. Recovery to baseline or Grade1 NCI CTCAE v5.0 from toxicities related to any prior treatments, unless adverse events are clinically nonsignificant and/or stable in the opinion of the investigator.
5. Age\>18 years of age
6. Karnofsky performance score ≥60%
7. Patients must have adequate organ and marrow function as defined below:

   * absolute neutrophil count ≥1,000/mcL
   * platelets ≥100,000/mcL
   * total bilirubin ≤ institutional upper limit of normal (ULN)
   * Aspartate Aminotransferase (AST) (SGOT)/Alanine Aminotransferase (ALT) (SGPT ≤3 × institutional ULN
   * creatinine ≤ institutional ULN OR
   * glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2

     1. Patients with abnormal test results outside the allowable range, but are not clinically significant, may still enroll with PI's review and approval.
     2. Laboratory reference values should account for potential normal variations due to race, ethnicity, age, sex, and gender identity (e.g., due to surgical and/or hormonal changes).
8. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
9. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
10. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
11. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
12. Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
13. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
14. Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
15. Patients who agree to use an adequate method of contraception throughout the study period, starting with the administration of 89Zr-DFO-girentuximab,
16. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia.
2. Patients who are receiving any other investigational agents.
3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to girentuximab.
4. Patients with uncontrolled intercurrent illness at the discretion of the investigator.
5. Pregnant women are excluded from this study because belzutifan is an agent with the potential for teratogenic or abortifacient effects.

Where this trial is running

New York, New York

• NYU Langone Health — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: Minas Economides, MD — NYU Langone Health
• Study coordinator: Cancer Trials (NYU Langone Health Perlmutter Cancer Center)

Conditions Metastatic Clear Cell Renal Cell Carcinoma