Effects of Belzutifan on 89Zr-DFO-girentuximab PET Uptake in Patients With Renal Cell Carcinoma (RCC)

NCT07179770 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 2 other identifiers: 24-012545K12CA270377-02
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to identify changes in Carbonic Anhydrase IX (CAIX) expression induced by hypoxia-inducible factor 2 alpha (HIF-2α) inhibition by initiating belzutifan single agent therapy and imaging CAIX expression with 89Zr-DFO-girentuximab PET before and 4 weeks after initiating treatment. This will be the first study to evaluate potential changes in CAIX expression altered by belzutifan. Information gained from this study will be leveraged to develop combinations of belzutifan with CAIX targeted agents including radioimmunotherapy in the future.

Conditions

Metastatic Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (3)

• Change in Standardized Uptake Value (SUV) max uptake on 89Zr-DFO-girentuximab PET in ccRCC lesions between baseline and 4 weeks after initiation of belzutifan treatment

  Baseline, Week 4

• Standardized Uptake Value (SUV) peak uptake on 89Zr-DFO-girentuximab PET in ccRCC lesions between baseline and 4 weeks after initiation of belzutifan treatment

  Baseline, Week 4

• Occurrence of one or more grade 3 or higher toxicities by CTCAE v5 criteria

  Week 4

Study Arms (1)

Previously treated metastatic clear cell RCC

EXPERIMENTAL

Patients will undergo imaging with \[89Zr\]Zr-DFO-girentuximab PET before and 28 days after treatment with belzutifan.

Drug: Belzutifan; Drug: 89Zr-DFO-girentuximab; Device: 89Zr-DFO-girentuximab PET

Interventions

Belzutifan DRUG

120 mg orally daily for 28 days

Also known as: Welireg®

Previously treated metastatic clear cell RCC

89Zr-DFO-girentuximab DRUG

10 mg single slow intravenous (IV) administration

Also known as: TLX250-CDx

Previously treated metastatic clear cell RCC

89Zr-DFO-girentuximab PET DEVICE

89Zr-DFO-Girentuximab PET before and after 4 weeks of treatment with standard-of-care (SOC) belzutifan.

Previously treated metastatic clear cell RCC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed advanced clear cell RCC
• 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
• Measurable disease per RECIST v1.1
• 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.
• Age\>18 years of age
• Karnofsky performance score ≥60%
• 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

You may not qualify if:

• 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.
• Patients who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to girentuximab.
• Patients with uncontrolled intercurrent illness at the discretion of the investigator.
• Pregnant women are excluded from this study because belzutifan is an agent with the potential for teratogenic or abortifacient effects.

Sponsors & Collaborators

• NYU Langone Health: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinoma

Interventions

belzutifan

Study Officials

• Minas Economides, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer Trials (NYU Langone Health Perlmutter Cancer Center)

CONTACT

212-263-4432; CancerTrials@nyulangone.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2025
• First Posted: September 18, 2025
• Study Start: September 15, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)