EXACT: Randomized Phase II Trial of Zanzalintinib (XL092) in Combination With Immunotherapy in Patients Who Progress on Adjuvant Therapy in Clear Cell RCC

Status: Recruiting
Location: See all (2) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

The study population for this Phase 2 study will include men and women ≥ 18 with confirmed renal cell carcinoma who have progressed on adjuvant anti-PD-1/PD-L1 therapy, the current standard of care. Subjects will be randomized to Arm A or Arm B. Study treatment will be given in 28-day (4 week) cycles. Arm A treatment will consist of zanzalintinib (XL092) alone and will be taken once daily continuously (Day 1-Day 28). Arm B treatment will consist of XL092 plus nivolumab. XL092 will be taken once daily continuously (Day 1-Day 28) and nivolumab will be administered every 4 weeks (Day 1). Treatment will continue until progression by RECIST 1.1, toxicity, or other reasons as appropriate.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
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• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

• Age ≥ 18 years at the time of consent.

• ECOG Performance Status of 0-1 within 28 days prior to registration.

• Advanced or metastatic RCC with a clear cell component.

• Prior treatment must have included an anti-PD-1. Subjects must have progressed on or after adjuvant anti-PD-1 therapy. A washout period of 14 days prior to study treatment initiation is required. Subjects must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to Grade ≤ 1 or baseline. Unresolved grade 2 or greater toxicity from prior checkpoint inhibitor therapy will exclude a subject from enrolling. Subjects that received other systemic therapy after anti-PD1 are not eligible.

• Measurable disease per RECIST 1.1.

• Demonstrate adequate organ function as defined below. All screening labs are to be obtained within 2 weeks prior to registration.

‣ Absolute Neutrophil Count (ANC): ≥ 1500/mm3 without granulocytes colony-stimulating factor support within 2 weeks of screening laboratory collection

⁃ Platelet Count (PLT): ≥ 100,000/mm3; without transfusion within 2 weeks of screening laboratory sample collection.

⁃ Hemoglobin (Hgb): ≥ 9 g/dL

⁃ Serum Creatinine OR Calculated CrCl using Cockgroft Gault equation: Serum creatinine \< 1.5 upper limit of normal (ULN) OR calculated Cr Clearance \>40mL/min

⁃ Urine protein-to-creatinine ratio (UPCR): ≤1mg/mg (≤ 113.2mg/mmol) creatinine

⁃ Bilirubin: ≤ 1.5 × ULN (for subjects with Gilbert's disease \< 3 x ULN)

⁃ Aspartate aminotransferase (AST): ≤ 3 × ULN

⁃ Alanine aminotransferase (ALT): ≤ 3 × ULN

⁃ Alkaline phosphatase (ALP): ≤ 3 × ULN. For subjects with documented bone metastasis ALP ≤ 5x ULN

⁃ International Normalized Ratio (INR): ≤ 1.5 x ULN

⁃ Activated Partial Thromboplastin Time (aPTT): ≤ 1.2 × ULN

• Females of childbearing potential must have a negative urine or serum pregnancy test within 2 weeks prior to registration. If a urine test is done and it is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

• Females of childbearing potential who are sexually active with a male able to father a child must be willing to abstain from penile-vaginal intercourse or to use an effective method(s) of contraception. Males able to father a child who are sexually active with female of childbearing potential must be willing to abstain from penile-vaginal intercourse or to use an effective method(s) of contraception.

⁃ Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial. Testing is not required at screening unless mandated by local policy.

⁃ Patients with known chronic hepatitis B virus (HBV) infection, must have an undetectable HBV viral load on suppressive therapy, if indicated. 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, the HCV viral load must be undetectable to be eligible for this trial. Testing is not required at screening unless mandated by local policy.

⁃ As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Locations
United States
Missouri
Washington University School of Medicine
RECRUITING
St Louis
New York
Columbia University Irving Medical Center
RECRUITING
New York
Contact Information
Primary
Karie Runcie, MD
kr2836@cumc.columbia.edu
212-305-5098
Backup
Gabrielle Tiggs
gtiggs@hoosiercancer.org
317-634-5842
Time Frame
Start Date: 2025-12
Estimated Completion Date: 2028-12
Participants
Target number of participants: 70
Treatments
Experimental: Arm A: XL092
Study treatment will be given in 28-day (4 week) cycles. Arm A treatment will consist of XL092 60 mg orally alone and will be taken once daily continuously (Day 1-Day 28). Treatment will continue until progression by RECIST 1.1, toxicity, or other reasons as appropriate.
Experimental: Arm B: XL092 and Nivolumab
Study treatment will be given in 28-day (4 week) cycles. Arm B treatment will consist of XL092 60 mg plus nivolumab 480 mg intravenously. XL092 will be taken once daily continuously (Day 1-Day 28) and nivolumab will be administered every 4 weeks (Day 1). Treatment will continue until progression by RECIST 1.1, toxicity, or other reasons as appropriate.
Related Therapeutic Areas
Sponsors
Collaborators: Columbia University, Exelixis
Leads: Karie Runcie

This content was sourced from clinicaltrials.gov