Patients With Locally Advanced or Metastatic But Resectable Clear Cell Renal Cell CarcinomaPhase 2NCT07691476

A Phase 2 Multicenter Single-Arm Clinical Trial of Zanzalintinib and Pembrolizumab in Subjects With Resectable Clear Cell Renal Cell Carcinoma

A Phase 2 study testing Zanzalintinib and Pembrolizumab in people with Patients With Locally Advanced or Metastatic But Resectable Clear Cell Renal Cell Carcinoma, run by Yonsei University.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

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Trial summary

This is a multicenter, single-arm, phase 2 clinical trial designed to evaluate the clinical efficacy of combination therapy with zanzalintinib and pembrolizumab in patients with locally advanced intermediate- to high-risk, high-risk, or resectable metastatic clear cell renal cell carcinoma. Read more about this study

Who is it for?: Ages 19 years and older
Conditions the study is for: Patients With Locally Advanced or Metastatic But Resectable Clear Cell Renal Cell Carcinoma
What is being tested?: Zanzalintinib and Pembrolizumab
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 48 participants
Where: No sites listed yet
Study dates: 1 Oct 2026to 1 Feb 2029
Phase: Phase 2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 19 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects with clear cell renal cell carcinoma (clear cell RCC) confirmed by pathological or cytological diagnosis.
meeting one or more of the following criteria:
Locally advanced disease or resectable metastatic disease.
Resectable intermediate- to high-risk or high-risk patients are eligible for enrollment.
Resectability is determined by multidisciplinary Resectability will be determined based on multidisciplinary evaluation. Resectable metastatic disease is defined as cases in which, in the presence of a primary tumor, complete resection of both the primary tumor and all identifiable metastatic lesions is deemed feasible by multidisciplinary assessment. All metastatic lesions must be amenable to complete resection within the planned surgical schedule. Subjects will be excluded from enrollment if metastatic lesions have already been completely resected prior to study entry, are deemed unresectable, or are expected to have residual disease after attempted resection.
Intermediate-High Risk Group cT2· Grade 4· or· Sarcomatoid cT3, any Grade, N0 High Risk Group cT4, any Grade, N0 any cT, any Grade, N+ Resectable Metastatic Disease any cT, any cN, any Grade, M1

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Age 19 years or older on the day of consent
ECOG performance status 0~1
Female subjects of childbearing potential must have a negative result on a serum or urine pregnancy test conducted during the clinical trial screening period. If the urine test result is positive or cannot be confirmed as negative, a serum pregnancy test must be performed.
Sexually active fertile subjects and their partners must agree to use highly effective method of contraception (defined in Appendix E) during the course of the study and for a specified period after the last dose of treatment, as defined below. Subjects and their partners must consistently use highly effective contraception, and an additional contraceptive method (e.g., condom) is required.
Male subjects: Must use a condom during the treatment period and for 120 days after the last dose and must agree not to donate sperm during this period.
Female subjects: Women of childbearing potential (WOCBP) must comply with protocol-specified contraceptive methods during the treatment period and for 186 days after the last dose.
The durations reflect the longer washout period between Zanzalintinib and Pembrolizumab.
Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 as determined by the Investigator.
Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
Adequate organ and marrow function as defined by the table below.
Table 2. Organ function requirements for eligibility evaluation Organ System Laboratory Test Criteria Hematological Absolute neutrophil count (ANC) ≥1,500/μL Platelets ≥100,000/μL Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L Renal Creatinine OR creatinine clearance (CrCl) (If CrCl is used, estimated GFR may also be acceptable) ≤1.5 × ULN OR CrCl ≥60 mL/min (if applicable to the study population)
Urine protein-to-creatinine ratio (UPCR) ≤1.5 mg/mg Hepatic
Total bilirubin ≤1.5 × ULN OR, if subject has known Gilbert's syndrome:
direct bilirubin ≤1.5 × ULN (Subjects with other causes of hyperbilirubinemia: total bilirubin ≤3 × ULN and ALT <3 × ULN) AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (or ≤5 × ULN for subjects with liver metastasis) Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) ≤1.5 × ULN, or if the subject is receiving anticoagulant therapy within the treatment range, no restrictions apply.

Who cannot join

Concurrent anticancer treatments other than the investigational therapy, including chemotherapy, curative radiotherapy, surgery, immunotherapy, biological therapy, or tumor embolization.
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.
Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
History of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2 therapies, or vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors.
Any complementary medicine within 2 weeks prior to first dose of treatment.
History of another malignancy within the 2 years prior to the first dose of study treatment, except for basal cell carcinoma or squamous cell carcinoma treated solely by local excision, cervical carcinoma in situ, or completely resected papillary thyroid carcinoma.

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Diagnosis of immunodeficiency or is receiving systemic steroid therapy (> 10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment. Inhaled, intranasal, intraarticular, and topical corticosteroids and mineralocorticoids are allowed
Presence of untreated fistulas, irrespective of cancer status.
Presence of uncontrolled concomitant diseases, including but not limited to ongoing or active infections, symptomatic congestive heart failure, unstable angina, cardiac arrhythmias, immunosuppressive conditions, autoimmune diseases, underlying pulmonary disorders, or psychiatric or social conditions that may limit compliance with clinical trial requirements.
Active autoimmune diseases requiring systemic treatment (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years before the treatment of trial. Physiologic corticosteroid replacement for thyroid hormone, insulin, or adrenal/pituitary insufficiency is excluded from this criterion.
Thrombotic, embolic, venous, or arterial events (e.g., cerebrovascular accident including transient ischemic attack, deep vein thrombosis, pulmonary embolism) within 6 months before the treatment of trial.
Concomitant anticoagulation with oral anticoagulants and platelet inhibitors. Only low-dose aspirin and LMWH are permitted.
Subjects must have discontinued anticoagulant within 3 days or 5 half-lives prior to the first dose of treatment (whichever is longer)
History of non-infectious pneumonitis requiring corticosteroid therapy or presence of current pneumonitis.
Uncontrolled hypertension (>140 mmHg systolic or >90 mmHg diastolic despite optimal antihypertensive treatment
Prior history of myocarditis
Known gastric or esophageal varices
Ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks
Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 tsp of red blood, or other history of significant bleeding within 12 weeks before first dose of study treatment
Symptomatic cavitating pulmonary lesion(s) or endobronchial disease (asymptomatic or radiated lesions allowed)
Lesions invading or encasing any major blood vessels
Serious non-healing wound/ulcer/bone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions
Malabsorption syndrome
Pharmacologically uncompensated, symptomatic hypothyroidism
Moderate to severe hepatic impairment (Child-Pugh B-C)
Requirement for hemodialysis or peritoneal dialysis
History of solid organ or allogeneic stem cell transplant
Major surgery within 8 weeks or minor surgery within 14 days prior to study treatment. Subjects must have complete wound healing following major or minor surgery prior to the first dose of study treatment.
If a tumor biopsy is performed prior to treatment initiation, study treatment may only be initiated after at least 14 days have elapsed from the date of the biopsy and complete wound healing at the biopsy site has been clinically confirmed.
Complete wound healing is defined as closure of the biopsy site without the need for dressing, and absence of active bleeding, hematoma, infection, erythema, drainage, worsening pain, or wound dehiscence.
If complications such as bleeding, hematoma, infection, persistent pain, drainage, wound dehiscence, or any complication requiring additional intervention occur after biopsy, study treatment must not be initiated until such complications have resolved and complete wound healing has been confirmed.
The investigator may further delay the initiation of study treatment if additional waiting time is considered necessary, taking into account the biopsy location, procedure, and risk of bleeding.
History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
Inability to swallow tablets or ingest a suspension either orally or by a NG or PEG tube
Previously identified allergy or hypersensitivity to components of treatment
Other conditions, which in the opinion of the investigator, would compromise the safety of the patient or the patient's ability to complete the study
Known positive test for tuberculosis infection if supported by clinical or radiographic evidence of disease
History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field is permitted.
Free thyroxine (FT4) outside the laboratory normal reference range. Asymptomatic subjects with FT4 abnormalities can be eligible after Principal Investigator approval.
Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.
Pregnancy or breastfeeding. Negative serum or urine pregnancy test results must be confirmed within 1 week before the treatment of trial.
History of HIV infection or chronic or active hepatitis C requiring antiviral therapy. In cases of hepatitis B, enrollment is permitted if the patient is receiving appropriate antiviral treatment and viral DNA is undetectable.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Sang Joon Shin, Professor contact

02-2228-8138

ssj338@yuhs.ac

About this study

The neoadjuvant treatment period consists of a total of 6 cycles; pembrolizumab is administered every 3 weeks, and zanzalintinib is administered orally once daily. A drug washout period of at least 21 days is required prior to the last dose before surgery.

Surgery will be performed after completion of the neoadjuvant treatment and following a drug washout period of at least 21 days.

The adjuvant treatment period begins at least 28 days after surgery, and pembrolizumab is administered every 3 weeks for a total of 11 cycles.

Radiologic response assessments are conducted at predefined time points during the neoadjuvant period, and pathologic response is evaluated using resected tissue obtained at the time of surgery.

Study duration: Approximately 30 months (18 months for enrollment + 12 months for treatment and follow-up)
Planned sample size: 48 patients (including an estimated 10% dropout rate) Tumor size and disease stage will be assessed using baseline imaging performed prior to treatment, and tumor response will be evaluated through predefined scheduled imaging assessments conducted during treatment. Tumor response will be evaluated during treatment via imaging at regular intervals per cycle. Surgery will be scheduled after the completion of 6 cycles, following a minimum 21-day washout period (±7 days at the investigator's discretion). If postoperative recovery is adequate (at least 28 days, ±14 days at the investigator's discretion), adjuvant Pembrolizumab treatment will commence.

Conditions: Patients With Locally Advanced or Metastatic But Resectable Clear Cell Renal Cell Carcinoma
Being tested: Zanzalintinib and Pembrolizumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Zanzalintinib and PembrolizumabDrug
Treatment consists of a neoadjuvant and an adjuvant phase, during which Zanzalintinib and Pembrolizumab are administered. Patients will receive a total of 6 cycles (21 days per cycle) of combination therapy as neoadjuvant treatment, followed by surgery. After srugery, patients will receive 11 additional cycles of adjuvant Pembrolizumab.

Study groups in NCT07691476
Study group	Role	What they receive
Combination Therapy of Zanzalintinib and Pembrolizumab	Experimental	Treatment consists of a neoadjuvant and an adjuvant phase, during which Zanzalintinib and Pembrolizumab are administered. Patients will receive a total of 6 cycles (21 days per cycle) of combination therapy as neoadjuvant treatment, followed by surgery. After srugery, patients will receive 11 additional cycles of adjuvant Pembrolizumab. Receives: Drug: Zanzalintinib and Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall Response Rate
Tumor response will be evaluated radiologically in accordance with RECIST version 1.1 and defined as the proportion of complete response (CR) or partial response (PR). As a primary endpoint, the objective response rate will be assessed every 9 weeks (±7 days) during the neoadjuvant treatment period.
Measured: Preoperatively, up to 22 weeks

Secondary outcomes (10)

safety and tolerability
Incidence of adverse events (AEs) and serious adverse events (SAEs) based on CTCAE version 5.0 criteria.
Measured: Perioperatively, up to 59 weeks
major pathologic response
Defined as 10% or less residual viable tumor in the resected specimen.
Measured: Major pathological response (MPR) will be assessed during the surgical period.
event-free survival, EFS
Time from treatment initiation to the occurrence of the first event, including relapse, progression, or death.
Measured: Up to 5 years
overall survival, OS
Time from treatment initiation to death from any cause.
Measured: Up to 5 years
Surgery completion rate
Proportion of subjects who underwent the planned surgery after initiation of neoadjuvant therapy.
Measured: From treatment initiation to surgery
Pathologic complete resection rate (R0)
Proportion of subjects with microscopically margin-negative (R0) resection confirmed by pathological assessment.
Measured: At the time of surgery
Surgery delay rate (>4 weeks)
Proportion of subjects whose surgery was delayed by more than 4 weeks from the initially planned date due to treatment-related adverse events or medical reasons.
Measured: From planned surgery date to actual surgery date (up to 4 weeks after the planned surgery date)
Reoperation rate
Proportion of subjects who required reoperation due to postoperative complications or residual disease.
Measured: Within 12 weeks after surgery
Postoperative Complications
Incidence of complications occurring within 12 weeks following surgery.
Measured: Within 12 weeks after surgery
Surgery-related mortality
Proportion of subjects who died due to surgery-related causes within 12 weeks after surgery.
Measured: Within 12 weeks after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Oct 20261 Feb 2029

First posted9 Jul 2026
Study start1 Oct 2026 (estimated)
Primary completion31 Oct 2028 (estimated)
Study completion1 Feb 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Patients With Locally Advanced or Metastatic But Resectable Clear Cell Renal Cell CarcinomaStudies of the same condition, open and under way.
More trials run by Yonsei UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 48 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07691476
Sponsor's protocol ID: 4-2025-1718
Status last verified: Jul 2026
First submitted: 14 Jun 2026
Last updated: 9 Jul 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2 Multicenter Single-Arm Clinical Trial of Zanzalintinib and Pembrolizumab in Subjects With Resectable Clear Cell Renal Cell Carcinoma
ClinicalTrials.gov ID: NCT07691476
Acronym / sponsor ID: 4-2025-1718
Conditions: Patients With Locally Advanced or Metastatic But Resectable Clear Cell Renal Cell Carcinoma
Phase: Phase 2
Study type: Interventional
Recruitment status: Not yet recruiting
Enrolment: 48 participants (estimated)
Lead sponsor: Yonsei UniversityUniversity, hospital or other
Study start: 1 Oct 2026 (estimated)
Primary completion: 31 Oct 2028 (estimated)
Study completion: 1 Feb 2029 (estimated)
First posted: 9 Jul 2026 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Surgery will be performed after completion of the neoadjuvant treatment and following a drug washout period of at least 21 days.

The adjuvant treatment period begins at least 28 days after surgery, and pembrolizumab is administered every 3 weeks for a total of 11 cycles.

Radiologic response assessments are conducted at predefined time points during the neoadjuvant period, and pathologic response is evaluated using resected tissue obtained at the time of surgery.

Study duration: Approximately 30 months (18 months for enrollment + 12 months for treatment and follow-up)
Planned sample size: 48 patients (including an estimated 10% dropout rate) Tumor size and disease stage will be assessed using baseline imaging performed prior to treatment, and tumor response will be evaluated through predefined scheduled imaging assessments conducted during treatment. Tumor response will be evaluated during treatment via imaging at regular intervals per cycle. Surgery will be scheduled after the completion of 6 cycles, following a minimum 21-day washout period (±7 days at the investigator's discretion). If postoperative recovery is adequate (at least 28 days, ±14 days at the investigator's discretion), adjuvant Pembrolizumab treatment will commence.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Combination Therapy of Zanzalintinib and Pembrolizumab	Experimental	Drug: Zanzalintinib and PembrolizumabTreatment consists of a neoadjuvant and an adjuvant phase, during which Zanzalintinib and Pembrolizumab are administered. Patients will receive a total of 6 cycles (21 days per cycle) of combination therapy as neoadjuvant treatment, followed by surgery. After srugery, patients will receive 11 additional cycles of adjuvant Pembrolizumab.

Who may qualify

Ages: 19 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (20 listed)

Subjects with clear cell renal cell carcinoma (clear cell RCC) confirmed by pathological or cytological diagnosis.
Intermediate-High Risk Group cT2· Grade 4· or· Sarcomatoid cT3, any Grade, N0 High Risk Group cT4, any Grade, N0 any cT, any Grade, N+ Resectable Metastatic Disease any cT, any cN, any Grade, M1
Age 19 years or older on the day of consent
ECOG performance status 0~1
Female subjects of childbearing potential must have a negative result on a serum or urine pregnancy test conducted during the clinical trial screening period. If the urine test result is positive or cannot be confirmed as negative, a serum pregnancy test must be performed.

Key exclusion criteria (42 listed)

Concurrent anticancer treatments other than the investigational therapy, including chemotherapy, curative radiotherapy, surgery, immunotherapy, biological therapy, or tumor embolization.
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.
Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
History of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2 therapies, or vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors.
Any complementary medicine within 2 weeks prior to first dose of treatment.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Zanzalintinib and PembrolizumabTreatment consists of a neoadjuvant and an adjuvant phase, during which Zanzalintinib and Pembrolizumab are administered. Patients will receive a total of 6 cycles (21 days per cycle) of combination therapy as neoadjuvant treatment, followed by surgery. After srugery, patients will receive 11 additional cycles of adjuvant Pembrolizumab.	Drug	Combination Therapy of Zanzalintinib and Pembrolizumab

Primary outcome

Overall Response Rate
Time frame: Preoperatively, up to 22 weeks
Tumor response will be evaluated radiologically in accordance with RECIST version 1.1 and defined as the proportion of complete response (CR) or partial response (PR). As a primary endpoint, the objective response rate will be assessed every 9 weeks (±7 days) during the neoadjuvant treatment period.

10 secondary outcomes

safety and tolerability
Time frame: Perioperatively, up to 59 weeks
major pathologic response
Time frame: Major pathological response (MPR) will be assessed during the surgical period.
event-free survival, EFS
Time frame: Up to 5 years
overall survival, OS
Time frame: Up to 5 years
Surgery completion rate
Time frame: From treatment initiation to surgery
Pathologic complete resection rate (R0)
Time frame: At the time of surgery
Surgery delay rate (>4 weeks)
Time frame: From planned surgery date to actual surgery date (up to 4 weeks after the planned surgery date)
Reoperation rate
Time frame: Within 12 weeks after surgery
Postoperative Complications
Time frame: Within 12 weeks after surgery
Surgery-related mortality
Time frame: Within 12 weeks after surgery

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2026.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Sang Joon Shin, Professor contact

02-2228-8138

ssj338@yuhs.ac

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zanzalintinib and Pembrolizumab in people with Patients With Locally Advanced or Metastatic But Resectable Clear Cell Renal Cell Carcinoma, run by Yonsei University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sang Joon Shin, Professor (02-2228-8138, ssj338@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (time frame: Preoperatively, up to 22 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07691476.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2026.