Trial of Zanzalintinib (XL092) in Combination With Immunotherapy in Patients Who Progress on Adjuvant Therapy in Clear Cell RCC

NCT06863311 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN-GU22-595
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Advanced Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR is defined as the proportion of patients with partial response and complete response per RECIST version 1.1 criteria at any time prior to 6 months

  6 months

Secondary Outcomes (4)

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  2 years

• Progression Free Survival (PFS)

  2 years

• Overall Survival (OS)

  2 years

• Duration of Response (DoR)

  2 years

Study Arms (2)

Arm A: XL092

EXPERIMENTAL

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.

Drug: XL092

Arm B: XL092 and Nivolumab

EXPERIMENTAL

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.

Drug: XL092; Drug: Nivolumab

Interventions

XL092 DRUG

100 mg orally

Arm A: XL092; Arm B: XL092 and Nivolumab

Nivolumab DRUG

480 mg intravenously.

Arm B: XL092 and Nivolumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• Prior treatment with Zanzalintinib.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days prior to study treatment initiation.
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 28 days prior to study treatment initiation unless otherwise specified.
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• \. Radiation therapy for bone metastasis within 14 days, any other radiation therapy within 28 days prior to study treatment initiation. Systemic treatment with radionuclides within 6 weeks prior to study treatment initiation. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• \. Known brain metastases or cranial epidural disease. Subjects adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 28 days prior to study treatment initiation may be eligible. NOTE: Subjects with an incidental finding of an isolated brain lesion \< 1 cm in diameter may be eligible after sponsor-investigator approval if the lesion is radiographically stable for 28 days prior to study treatment initiation and does not require treatment per Investigator judgement. NOTE: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of study treatment initiation.
• \. Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 14 days prior to study treatment initiation.
• \. Active infection requiring systemic therapy. NOTE: Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• \. Positive TB test with active mycobacterial infection requiring systemic treatment.
• \. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• \. History of severe allergic anaphylactic reactions to study drug(s) or any of their excipients.
• \. Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial.
• \. Administration of a live, attenuated vaccine within 30 days prior to study treatment initiation.
• \. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis.
• \. Prior organ allograft including allogeneic stem cell transplant

Sponsors & Collaborators

• Karie Runcie: lead
• Exelixis: collaborator
• Columbia University: collaborator

Study Sites (2)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Nivolumab

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

• Karie Runcie, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karie Runcie, MD

CONTACT

212-305-5098; kr2836@cumc.columbia.edu

Allison Lipps

CONTACT

317-634-5842; alipps@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: March 3, 2025
• First Posted: March 7, 2025
• Study Start: March 13, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

US (2)