Actively Recruiting

Phase 2
Age: 18Years +
All Genders
NCT06794229

Neoadjuvant Zanzalintinib Plus Nivolumab in Patients With Locally Advanced and/or Inoperable Clear Cell Renal Cell Carcinoma With or Without Non-measurable Metastasis

Led by Qian Qin · Updated on 2026-04-03

69

Participants Needed

1

Research Sites

187 weeks

Total Duration

On this page

Sponsors

Q

Qian Qin

Lead Sponsor

E

Exelixis

Collaborating Sponsor

AI-Summary

What this Trial Is About

All subjects will receive zanzalintinib 100mg orally (PO) once daily plus nivolumab standard of care dosing (i.e., 240mg IV every 2 weeks or 480mg IV every 4 weeks) for a total of 12 weeks, followed by restaging scan/evaluation for surgical operability and an adaptive approach that includes (1) surgical resection if the participant is eligible for surgery (Cohort A), (2) up to 48 weeks total (from Cycle 1 Day 1) of zanzalintinib plus nivolumab if the participant has partial response or stable disease but remains inoperable (Cohort B1), or (3) stopping protocol mandated treatment to receive standard of care systemic therapy and continue follow up per protocol if the participant has disease progression (Cohort B2).

CONDITIONS

Official Title

Neoadjuvant Zanzalintinib Plus Nivolumab in Patients With Locally Advanced and/or Inoperable Clear Cell Renal Cell Carcinoma With or Without Non-measurable Metastasis

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Provided written informed consent and HIPAA authorization
  • Age 18 years or older at consent
  • ECOG Performance Status of 0 or 1 within 30 days prior to registration
  • Histologically confirmed clear cell renal cell carcinoma with or without sarcomatoid features
  • Locally advanced (cT3/T4, N0-1) or deemed surgically inoperable
  • Non-measurable soft tissue metastasis less than 10 mm or lymph nodes less than 15 mm allowed
  • Recovered to baseline or Grade 1 or less severity from prior treatment adverse events
  • Adequate organ and marrow function meeting specific lab criteria within 30 days before treatment
  • Negative pregnancy test for females of childbearing potential within 48 hours of treatment start
  • Willingness to use contraception or abstain from sexual intercourse if of childbearing potential
  • Able to understand and comply with study procedures for entire study duration
Not Eligible

You will not qualify if you...

  • Non-clear cell kidney cancer histology
  • Measurable metastatic disease or certain non-measurable lesions including bone metastasis
  • Prior systemic therapy for renal cell carcinoma including zanzalintinib or nivolumab
  • Prior surgery or radiation to the primary kidney tumor of interest within 4 weeks
  • Use of certain anticoagulants or platelet inhibitors not allowed
  • Use of complementary medications like herbal supplements within 2 weeks before treatment
  • Uncontrolled or recent serious illnesses including unstable heart conditions, uncontrolled hypertension, recent stroke or clotting events
  • Significant gastrointestinal disorders or recent abdominal complications
  • Active infection requiring systemic treatment
  • Known active hepatitis B or C infection
  • Known HIV infection unless stable on therapy with specific criteria
  • Serious non-healing wounds or fractures
  • Malabsorption syndrome
  • Uncontrolled hypothyroidism
  • Moderate to severe liver impairment
  • Need for dialysis
  • History of organ or stem cell transplant
  • Major surgery within 8 weeks or minor surgery within 5 days prior to treatment
  • Prolonged QTc interval on ECG
  • Psychiatric illness interfering with consent or compliance
  • Pregnant or breastfeeding females
  • Inability to swallow tablets or ingest medication by tube
  • Allergies to study drug components
  • Other malignancies requiring treatment interfering with study
  • Active or suspected autoimmune diseases except certain controlled conditions
  • Positive tuberculosis test with disease evidence
  • History or evidence of certain lung diseases or active pneumonitis
  • Abnormal thyroid hormone levels without approval
  • Immunodeficiency or recent systemic immunosuppressive therapy
  • Live vaccine within 30 days before treatment start

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 1 location

1

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

Actively Recruiting

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Research Team

Q

Qian Qin, MD

CONTACT

A

Ahran Lee

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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