Phase 1b/2 Study of Combination 177Lu Girentuximab Plus Cabozantinib and Nivolumab in Treatment naïve Patients With Advanced Clear Cell RCC

NCT05663710 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 2021-0911NCI-2022-10595CDMRP-KC210253
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if giving 177Lu girentuximab in combination with cabozantinib plus nivolumab can help to control advanced clear cell renal cell carcinoma (ccRCC).

Conditions

Advanced Cancer; Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year

Study Arms (3)

Cohort 1 (Biopsy)

EXPERIMENTAL

Participants within 2 weeks of starting the first dose of 177Lu-girentuximab

Drug: 177Lu girentuximab; Drug: Nivolumab; Drug: Cabozantinib; Drug: ArabinoFuranosylGuanine [18F]F-AraG

Cohort 2 (Biopsy)

EXPERIMENTAL

Participants within 2 weeks of Cycle 4

Drug: 177Lu girentuximab; Drug: Nivolumab; Drug: Cabozantinib; Drug: ArabinoFuranosylGuanine [18F]F-AraG

Cohort 3 (Biopsy)

EXPERIMENTAL

Participants at the time of progression or at 20 months post treatment

Drug: 177Lu girentuximab; Drug: Nivolumab; Drug: Cabozantinib; Drug: ArabinoFuranosylGuanine [18F]F-AraG

Interventions

177Lu girentuximab DRUG

Given by IV (vein)

Cohort 1 (Biopsy); Cohort 2 (Biopsy); Cohort 3 (Biopsy)

Nivolumab DRUG

Given by IV (vein)

Also known as: BMS-936558, Opdivo

Cohort 1 (Biopsy); Cohort 2 (Biopsy); Cohort 3 (Biopsy)

Cabozantinib DRUG

Given by PO

Also known as: XL-184, XL184

Cohort 1 (Biopsy); Cohort 2 (Biopsy); Cohort 3 (Biopsy)

ArabinoFuranosylGuanine [18F]F-AraG DRUG

Given by IV (vein)

Cohort 1 (Biopsy); Cohort 2 (Biopsy); Cohort 3 (Biopsy)

Eligibility Criteria

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

You may qualify if:

• Has the ability to understand and willingness to sign a written ICF before the performance of any study-specific procedures on this protocol and 2022-0515
• Age ≥ 18 years
• Has locally advanced or metastatic RCC with predominantly clear cell subtype
• Has at least one measurable lesion as defined by RECIST version 1.1
• Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
• Has adequate organ function defined as follows:
• a. Absolute neutrophil count ≥ 1,500/µL, Hgb level ≥ 9 g/dL and platelet count (Plt) i. ≥ 100,000/µL without transfusion or growth factor support within 2 weeks prior to obtaining the hematology values at screening; b. Creatinine clearance ≥ 40 mL/min/1.73m2 c. Transaminase levels (AST/ALT) ≤ 3.0 × upper limit of normal (ULN); total bilirubin i. (TBILI) ≤ 1.5 mg/dL in the absence of Gilbert's disease
• Women of child beariring potential must have a negative serum preganancy test within 7 days before first study drug administration
• Female patients of child bearing potential, or a male patients with a female partner of child-bearing potential (defined as all women physiologically capable of becoming pregnant), must agree to use a highly effective method of contraception during screening, during the period of drug administration and for 120 days after stopping study drug administration. Highly effective contraception methods include the following:
• Total abstinence (defined as refraining from heterosexual intercourse during the entire period outlined above),
• Male or female sterilization, or
• Use of at least one of the following:
• Use of oral, injectable, transdermal, intravaginal, or implantable hormonal methods of contraception i. Combined estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation ii. Progestogen-only hormonal contraception associated with inhibition of ovulation c. Placement of an intrauterine device or intrauterine system
• Able to swallow oral medications
• Able to provide tumor tissue sample (archival or recent acquisition)

You may not qualify if:

• Has received treatment with any frontline systemic therapy for metastatic RCC
• Has a history of leptomeningeal disease or spinal cord compression
• Has a history of autoimmune disease requiring active therapy
• Has a history of brain metastases except:
• Patients may be enrolled if they have treated brain metastases with no evidence of progression or hemorrhage after therapy for brain metastases (e.g. radiation therapy, surgery, radiosurgery) AND
• Patients may be enrolled if they do not require ongoing treatment with dexamethasone or anti-epileptic drugs
• Has had radiation therapy for bone metastases within 2 weeks, or any other external radiation therapy (5 days or longer) to sites other than bone, within 4 weeks before administration of the first dose of study treatment. Patients with clinically relevant ongoing major complications from prior radiation therapy are not eligible.
• Has uncontrolled or poorly controlled hypertension, as defined by a sustained blood pressure (BP) \> 140/90 with or without antihypertensive treatment
• Has had any major cardiovascular event within 6 months prior to study drug administration including but not limited to myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, pulmonary embolism, clinically significant ventricular arrhythmias (e.g. sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes) or New York Heart Association Class III or IV heart failure
• Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results, in the opinion of the investigator or medical monitor
• Has an active infection requiring systemic treatment
• Is participating in another therapeutic clinical trial
• Is receiving chronic concomitant treatment with strong CYP3A4 inducers or CYP3A4 inhibitors
• Has manifestations of malabsorption due to prior gastrointestinal (GI) surgery or GI disease
• Has GI disorders including those associated with a high risk of perforation or fistula formation:

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• United States Department of Defense: collaborator
• Telix Pharmaceuticals (Innovations) Pty Limited: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Nivolumab; cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Eric Jonasch, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eric Jonasch, MD

CONTACT

(713) 563-7232; ejonasch@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: December 15, 2022
• First Posted: December 23, 2022
• Study Start: June 30, 2023
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (1)