Perioperative Trial With IO/TKI for Multi-stage Clear Cell Renal Cell Carcinoma

A Prospective, Open-label, Phase II Clinical Trial of Perioperative Toripalimab Plus Lenvatinib for Multi-stage Clear Cell Renal Cell Carcinoma (ccRCC)

Perioperative Trial With IO/TKI for Multi-stage Clear Cell Renal Cell Carcinoma (NCT07571551) is a Phase 2 interventional studying Clear Cell RCC, sponsored by Jinling Hospital, China. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

The IO/TKI regimens which combines Immune checkpoint inhibitors (IO) with Tyrosine Kinase Inhibitors (TKI) have become the standard first-line option for advanced ccRCC. Currently, IO/TKI regimens are serving as neoadjuvant treatment in arising clinical trials for ccRCC. Although anatomical change reflected by radiological response is reported in most neoadjuvant trials, only few studies focus on evaluation for pathological response in ccRCC. The TRIPLE-PATH trial is an investigator initiated prospective, open-label phase II trial with the main objective to evaluate the clinical activity of preoperative/neoadjuvant therapy of toripalimab plus lenvatinib as mesured by pathological response of resected primary lesion in multi-stage ccRCC. Patients with ccRCC will be enrolled into 3 different cohorts based on their clinical TNM at the time of screening: localized ccRCC (cT1-2N0M0), locally advanced ccRCC (cT3-4N0M0 or cTanyN1M0), and metastatic ccRCC (cTanyNanyM1). Toripalimab (240mg Q3W) will be administered intravenously on the 1st day, and lenvatinib (20mg QD) will be administered orally once daily of each 3 weeks cycle. Patients in all cohorts will receive 4 cycles of preopertive/neoadjuvant toripalimab (240mg Q3W IV) plus lenvatinib (20mg QD PO), and a subsequent partial/radical nephrectomy 7-10 days after the last cycle. For adjuvant/postoperative treatment, patients who undergo R0 resection presented with cT1-2aN0M0G4/cT2bN0M0G3-4/cT3-4N0M0Gany/cTanyN1M0Gany will receive adjuvant doses of toripalimab (240mg Q3W IV) for 17 cycles; patients who undergo simultaneous resection of all oligometastases considered as "no evidence of disease" (M1 NED) will also receive adjuvant doses of toripalimab (240mg Q3W IV) for 17 cycles; patients who undergo R1 resection or presented with M1 disease cannot be definitely resected will receive postoperative doses of toripalimab (240mg Q3W IV) plus lenvatinib (20mg QD PO) for 17 cycles. Specific follow-up for the enrolled patients is required in the TRIPLE-PATH trial. Longitudinal CT/MRI is utilized to assess the radiological response. Tissues and body fluid samples collected from the patients will be utilized for biomarker and multi-omic analysis. The primary endpoint of the TRIPLE-PATH trial is major pathological response (MPR) in the primary lesion according to the pathological response reporting guidelines by the International Neoadjuvant Kidney Cancer Consortium (INKCC). Simon's two-stage minimax design is adopted by TRIPLE-PATH. An initial of 12 patients per cohort (36 in total) will be recruited, following an interim analysis. Recruitment to any cohort will be suspended if MPR is not observed in any patient at the interim analysis. If MPR is observed in at least 1 patient, additional 9 patients will be recruited in each cohort to at most 21 patients. Considering potential 15% dropout rate in each cohort, an anticipation of 25 patients will be recruited for each cohort (75 in total) in this study.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Clear Cell RCC and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 75 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Clear Cell RCC subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - Patients have fully understood and give written willing to sign a consent form prior to receive neoadjuvant therapy. Patients with history of major psychiatric disease must be judged able to fully understand the trial, and the explicit consent of family members is required; - Patients with the ages range from 18 to 80 years old (at the time of signing willing to sign a consent form); - Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1; - Patients have at least 1 measurable target lesion according to RECIST v1.1. The target lesion can be biopsied as per protocol. - diagnosed by tissue sample (biopsy-confirmed) clear cell RCC; - Patients will be enrolled into 3 separate cohorts based on their clinical TNM at the time of baseline screening: 1. Cohort 1: localized ccRCC (cT1-2N0M0): the primary tumor in this cohort must meet the subsequent criteria: - The cT1a primary tumor should have ≥10 R.E.N.A.L. score, or locate in renal hilum close to renal artery or its main branch; - Patients with cT1b-2b primary tumors can be directly enrolled; - In case of necessary, patients will undergo dual radiological examinations using contrast-enhanced CT and MRI to rule out potential invasion of the renal pelvis or perirenal fat as per protocol. 2. Cohort 2: locally advanced ccRCC (cT3-4N0M0 or cTanyN1M0); 3. Cohort 3: metastatic ccRCC (cTanyNanyM1): the patients should be evaluated as suitable for cytoreductive nephrectomy. - Patient have no symptomatic metastatic lesions requiring urgent intervention; - The sum of the diameters of the other target lesions (excluding the primary tumor) does not exceed the longest diameter of the primary tumor. - The patients who are treatment-naive, and have not received systemic therapy for any tumor; - Adequate main organ function. The screening laboratory indicators must meet the following criteria: 1. blood count (hemoglobin) at least 90 g/L (Without blood transfusion); ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * Patients have fully understood and give written informed consent prior to receive neoadjuvant therapy. Patients with history of major psychiatric disease must be judged able to fully understand the trial, and the explicit consent of family members is required; * Patients with the ages range from 18 to 80 years old (at the time of signing informed consent); * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1; * Patients have at least 1 measurable target lesion according to RECIST v1.1. The target lesion can be biopsied as per protocol. * Histologically confirmed clear cell RCC; * Patients will be enrolled into 3 separate cohorts based on their clinical TNM at the time of baseline screening: 1. Cohort 1: localized ccRCC (cT1-2N0M0): the primary tumor in this cohort must meet the subsequent criteria: * The cT1a primary tumor should have ≥10 R.E.N.A.L. score, or locate in renal hilum close to renal artery or its main branch; * Patients with cT1b-2b primary tumors can be directly enrolled; * In case of necessary, patients will undergo dual radiological examinations using contrast-enhanced CT and MRI to rule out potential invasion of the renal pelvis or perirenal fat as per protocol. 2. Cohort 2: locally advanced ccRCC (cT3-4N0M0 or cTanyN1M0); 3. Cohort 3: metastatic ccRCC (cTanyNanyM1): the patients should be evaluated as suitable for cytoreductive nephrectomy. * Patient have no symptomatic metastatic lesions requiring urgent intervention; * The sum of the diameters of the other target lesions (excluding the primary tumor) does not exceed the longest diameter of the primary tumor. * The patients who are treatment-naive, and have not received systemic therapy for any tumor; * Adequate main organ function. The screening laboratory indicators must meet the following criteria: 1. Hemoglobin ≥ 90 g/L (Without blood transfusion); 2. Platelets count ≥ 100 x 109/L; 3. Absolute neutrophil count ≥ 1.5 x 109/L; 4. Serum creatinine ≤ 1.5 x ULN, or eGFR \> 60 mL/min/1.73m2; 5. Total bilirubin ≤ 1.5 mg/dL; 6. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 x ULN for patients without evidence of liver metastases; AST and/or ALT ≤ 5 x ULN for patients with liver metastases; 7. Normal CK; 8. Normal Troponin T; 9. Normal LDH. * Willingness and ability to comply with planned visits, therapeutic laboratory testing, and other procedures. Exclusion Criteria: * Signs of tumor metastasis involving the central nervous system, or radiological evidence of brain metastasis; * History of malignant tumors other than ccRCC within the previous 5 years, with the exception of malignant tumors that can be expected to be cured with treatment (including but not limited to adequately treated thyroid cancer, carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated with radical surgery); * Prior to participating in the study, patients have received prior immune checkpoint inhibitors, investigational drugs or device therapy; * History of undergoing major surgery (judged by the investigator) within 4 weeks before the first trial dose, are recovering, or are unable to undergo baseline puncture; * History of severe drug allergy, including but not limited to antibody drugs; * Patients with contraindications to immunotherapy restart, including but not limited to: 1. Grade 2-4 immune myocarditis; 2. Severe grade 4 proteinuria; 3. Severe or life-threatening grade 4 immune hepatitis; 4. Severe grade 3-4 immune pneumonitis; 5. Severe inflammatory arthritis that significantly affects daily life or quality of life; 6. Severe neurological toxicity: 7. Myasthenia gravis grade 2-4; 8. Guillain-Barre syndrome (GBS) or transverse myelitis of any grade; 9. Grade 2-4 encephalitis; 10. Severe or life-threatening grade 3-4 pancreatitis; 11. Severe or life-threatening bullous disease (grade 3-4); 12. Severe grade 3-4 uveitis or episcleritis. * Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation or long-term corticosteroid therapy. * Non-resolution of toxicity after previous antineoplastic therapy, i.e., resolution to baseline, CTCAE v5.0 grade 0-1 (excluding alopecia), or inclusion/exclusion criteria. Irreversible toxicities (e.g., hearing loss) that would not reasonably be expected to be exacerbated by the study drug can be included in the study; * Known history of clinically significant liver disease, including active viral hepatitis (hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HbcAb) positive, HBV DNA\>10000 copies /mL or \>2000 IU/mL; Hepatitis C virus (HCV) antibody positive and HCV RNA positive), or other active hepatitis, clinically significant moderate to severe cirrhosis; * Patients with uncontrolled third space effusion requiring repeated drainage, such as pleural effusion, ascites, pericardial effusion, etc. (Patients who do not need drainage of effusion or stop drainage for 3 days without significant increase in effusion can be enrolled); * Receiving a systemic corticosteroid (prednisone \> 10mg/ day or equivalent) or other immunosuppressive medication within 14 days before the first study medication; * Patients with any severe and/or uncontrolled disease, including: 1. Hypertension that is not well controlled by antihypertensive medication; 2. Unstable angina pectoris or myocardial infarction, coronary artery bypass grafting or stent implantation within 6 months before study medication; 3. Grade I or above myocardial ischemia or myocardial infarction, arrhythmia (including QTc≥480ms) and ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification); Degree II or above heart block; Left ventricular ejection fraction (LVEF) \< 50%; 4. Poorly controlled diabetes (fasting blood glucose \> 10 mmol/L); 5. Patients with urinary protein ≥++ and confirmed 24-hour urinary protein \> 1.0g; 6. Severe active or uncontrolled infection. * Patients with or suspected to have active autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, etc.; * Renal failure requiring hemodialysis or peritoneal dialysis; * Patients with a history of immunodeficiency, including HIV positive patients, other acquired immunodeficiency diseases, congenital immunodeficiency diseases, or organ transplantation history; * History of live attenuated vaccine inoculation within 4 weeks before the first study drug or the expected vaccination during the study period; * History of psychiatric drug abuse and can not quit or have a history of mental disorders; * Women who are of childbearing potential. Women of childbearing potential must have a negative serum or urine pregnancy test, and must use appropriate methods of contraception. * The presence of any other severe, acute or chronic medical disease or mental illness or laboratory abnormality, as judged by the investigator, that may increase the risk associated with participation in the study or that may interfere with the interpretation of the results of the study.

Treatments Being Tested

DRUG

Toripalimab

Patients will receive 4 cycles of preoperative/neoadjuvant toripalimab (240mg Q3W IV) followed by a partial/radical nephrectomy 7-10 days after the last cycle. Patients who undergo R0 resection but presented with cT1-2aN0M0G4/cT2bN0M0G3-4/cT3-4N0M0Gany/cTanyN1M0Gany, or undergo simultaneous resection of all oligometastases considered as "no evidence of disease" (M1 NED), will receive 17 cycles of adjuvant toripalimab (240mg Q3W IV), starting at 4-8 weeks after surgery. Patients who undergo R1 resection or presented with M1 disease cannot be definitely resected will receive 17 cycles of postoperative toripalimab (240mg Q3W IV), starting at 4-8 weeks after surgery. Adjustment of dose: For patients with grade 3 or greater adverse events according to CTCAE v5.0 suspected to be caused by toripalimab, the dose can be postponed. In case of SAE, the dose can be discontinued. Dose de-escalation can be decided in patients who achieve MPR in primary lesions by investigators as per protocol.

DRUG

Lenvatinib

Patients will receive 4 cycles of preoperative/neoadjuvant lenvatinib (20mg QD PO) of each 3 weeks cycle followed by a partial/radical nephrectomy 7-10 days after the last cycle. Patients who undergo R1 resection or presented with M1 disease cannot be definitely resected will receive 17 cycles of postoperative lenvatinib (20mg) orally once daily of each 3 weeks cycle, starting at 4-8 weeks after surgery. Adjustment of dose: For patients with grade 3 or greater adverse events according to CTCAE v5.0 suspected to be caused by lenvatinib, the dosage can be gradually reduced to 16mg, 12mg and a minimal of 8mg. In case of SAE, the dose can be discontinued. Dose de-escalation can be decided in patients who achieve MPR in primary lesions by investigators as per protocol.

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University

Nanjing, Jiangsu, China

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT07571551), the sponsor (Jinling Hospital, China), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT07571551 clinical trial studying?

Who can participate in NCT07571551?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT07571551?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT07571551. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT07571551. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-26 · Data from ClinicalTrials.gov.