Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell CarcinomaPhase 2TL-SBRT-nccRCCNCT07922928
Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
A Phase 2 study testing Toripalimab, Lenvatinib and Stereotactic Body Radiotherapy in people with Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma, run by Sun Yat-sen University.
Trial summary
This single-center, nonrandomized, two-cohort Phase II study will evaluate neoadjuvant toripalimab and lenvatinib with or without stereotactic body radiotherapy (SBRT) in patients with resectable, nonmetastatic locally advanced non-clear cell renal cell carcinoma. Approximately 36 participants will be enrolled. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
- What is being tested?
- Toripalimab, Lenvatinib and Stereotactic Body Radiotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- No sites listed yet
- Study dates
- 10 Nov 2026to 31 Dec 2030
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntary written informed consent.
- Age 18 years or older.
- ECOG performance status of 0 or 1 and life expectancy of at least 6 months.
- Histologically confirmed, resectable, nonmetastatic locally advanced non-clear cell renal cell carcinoma, excluding chromophobe and collecting duct carcinoma. Eligible disease includes T3aNxM0, T3bNxM0 without level III or IV venous tumor thrombus, T4NxM0, or TxN1M0.
- At least one measurable lesion according to RECIST version 1.1.
- Adequate organ function: hemoglobin ≥80 g/L; absolute neutrophil count ≥1.5 × 10^9/L; white blood cell count ≥3.5 × 10^9/L; platelets ≥80 × 10^9/L; ALT and AST ≤2.5 × upper limit of normal (ULN); total bilirubin ≤1.5 × ULN; serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min; APTT, INR, and PT ≤1.5 × ULN.
- Women of childbearing potential must be confirmed not pregnant before enrollment. All participants must use adequate contraception during treatment and for 4 weeks after treatment completion.
- Willingness and ability to comply with study procedures.
Who cannot join
- Known hypersensitivity to toripalimab, lenvatinib, or their excipients.
- Chromophobe or collecting duct renal cell carcinoma.
- Anticancer monoclonal antibody or another investigational drug within 4 weeks before enrollment; prior PD-1/PD-L1-directed treatment for metastatic disease; or prior lenvatinib or another antiangiogenic drug.
- Distant organ metastasis or inability to undergo surgery.
- Systemic immunosuppressive treatment, including prednisone >10 mg/day or equivalent, within 2 weeks before enrollment.
- Active autoimmune disease, a history of autoimmune disease, or congenital or acquired immunodeficiency.
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- Poorly controlled cardiac disease, uncontrolled hypertension, or clinically significant cardiovascular events within 6 months before enrollment.
- Chemotherapy, targeted therapy, or radiotherapy within 2 weeks before enrollment.
- Gastrointestinal perforation or major surgery within 4 weeks before enrollment.
- Arterial or venous thromboembolic event within 6 months before enrollment, except resolved catheter-associated thrombosis as judged by the investigator.
- Active bleeding or a significant bleeding tendency, including clinically significant hemoptysis of more than 50 mL/day within 3 months before enrollment.
- Urine dipstick protein ≥2+ or 24-hour urine protein ≥1.0 g.
- Corrected QT interval >470 ms, subject to the protocol-specified review for pacemaker-related QT prolongation.
- Suspected additional primary malignancy.
- Interstitial lung disease, noninfectious pneumonitis, or another uncontrolled systemic disease.
- Live attenuated vaccine within 28 days before first treatment or planned live attenuated vaccination during the study.
- Active hepatitis B (HBV DNA ≥500 IU/mL), active hepatitis C (HCV RNA above the assay detection limit), or hepatitis B and C coinfection.
- Severe infection within 4 weeks before first treatment; CTCAE grade ≥2 active infection requiring systemic antibiotics within 2 weeks before first treatment; unexplained fever >38.5°C during screening or before first treatment unless attributed to the tumor by the investigator; or evidence of active tuberculosis within the preceding year.
- Prior or planned allogeneic bone marrow or solid-organ transplantation.
- Peripheral neuropathy of grade ≥2, active brain metastases, leptomeningeal disease, or spinal cord compression.
- Inability to swallow oral medication, chronic diarrhea, clinically significant intestinal obstruction, or another condition substantially affecting oral-drug absorption.
- Pregnancy, breastfeeding, or plans to become pregnant during the study.
- Any other serious physical or psychiatric illness or laboratory abnormality that may increase study risk, interfere with results, or make participation inappropriate in the investigator's judgment.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Single-Center, Two-Cohort Phase II Study of Neoadjuvant Toripalimab and Lenvatinib With or Without Stereotactic Body Radiotherapy in Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
This single-center, nonrandomized, two-cohort Phase II study will evaluate neoadjuvant toripalimab and lenvatinib with or without stereotactic body radiotherapy (SBRT) in patients with resectable, nonmetastatic locally advanced non-clear cell renal cell carcinoma. Approximately 36 participants will be enrolled. Both cohorts will receive six 21-day cycles of toripalimab and lenvatinib; one cohort will also receive SBRT to the primary renal tumor. Surgery is planned after neoadjuvant treatment. The primary outcome is the percentage of necrotic tumor cells in the resected tumor specimen.
Read the detailed description
Eligible participants with histologically confirmed, resectable, nonmetastatic locally advanced non-clear cell renal cell carcinoma will be enrolled into two nonrandomized cohorts. Cohort A will receive toripalimab 240 mg intravenously on day 1 of each 21-day cycle plus lenvatinib 12 mg orally once daily for six cycles. Cohort B will receive the same systemic treatment plus SBRT to the primary renal tumor at a total dose of 40 Gy in five fractions, delivered after completion of cycle 2 and before cycle 4. Tumor response will be assessed by imaging during and at the end of neoadjuvant treatment. Surgery will follow neoadjuvant treatment; the operating physician will determine the surgical approach based on imaging. Resected tumor specimens will be assessed for tumor cell necrosis and pathological response. Participants will be followed for recurrence, survival, and adverse events.
- Being tested
- Toripalimab, Lenvatinib, Stereotactic Body Radiotherapy
- Keywords
- Non-clear cell renal cell carcinoma; Neoadjuvant therapy; Toripalimab; Lenvatinib; Stereotactic body radiotherapy; Nephrectomy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToripalimabDrug
Toripalimab 240 mg by intravenous infusion on day 1 of each 21-day cycle for six cycles.
LenvatinibDrug
Lenvatinib 12 mg orally once daily during six 21-day cycles of neoadjuvant treatment.
Stereotactic Body RadiotherapyRadiation
SBRT to the primary renal tumor, 40 Gy in five fractions, after cycle 2 and before cycle 4.
| Study group | Role | What they receive |
|---|---|---|
| Toripalimab Plus Lenvatinib | Active comparator | Toripalimab 240 mg intravenously every 3 weeks plus lenvatinib 12 mg orally once daily for six 21-day cycles, followed by surgery. Receives: Drug: Toripalimab; Drug: Lenvatinib |
| Toripalimab Plus Lenvatinib and SBRT | Experimental | Toripalimab 240 mg intravenously every 3 weeks plus lenvatinib 12 mg orally once daily for six 21-day cycles. SBRT at 40 Gy in five fractions is delivered to the primary renal tumor after cycle 2 and before cycle 4, followed by surgery. Receives: Drug: Toripalimab; Drug: Lenvatinib; Radiation: Stereotactic Body Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Cell Necrosis Rate (TCNR)
Percentage of necrotic tumor cells in the resected tumor specimen, calculated from prespecified multisite pathological sampling.
Measured: At surgery following neoadjuvant treatment, approximately 5 to 6 months after the first dose.
Secondary outcomes (4)
R0 Resection Rate
Percentage of enrolled participants who undergo complete tumor resection with microscopically negative margins.
Measured: At surgery following neoadjuvant treatment, approximately 5 to 6 months after the first dose.
Objective Response Rate (ORR)
Percentage of participants with investigator-assessed complete or partial response according to RECIST version 1.1.
Measured: From baseline through the final preoperative tumor assessment, approximately 18 weeks.
Disease Control Rate (DCR)
Percentage of evaluable participants with complete response, partial response, or stable disease according to RECIST version 1.1.
Measured: From baseline through the final preoperative tumor assessment, approximately 18 weeks.
Major Pathological Response (MPR) Rate
Percentage of resected participants with no more than 10% residual viable tumor in the tumor bed.
Measured: At surgery following neoadjuvant treatment, approximately 5 to 6 months after the first dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2026
- Study start10 Nov 2026 (estimated)
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, ZHOU FANGJIAN, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07922928
- Sponsor's protocol ID
- 2024-FXY-233-Urology
- Other IDs
- 2024-FXY-233-Urology
- Acronym
- TL-SBRT-nccRCC
- Status last verified
- Nov 2026
- First submitted
- 2 Nov 2026
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared because this small study collects sensitive clinical, imaging, and molecular data that could increase the risk of participant re-identification. Study results will be reported in aggregate form.
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Center, Two-Cohort Phase II Study of Neoadjuvant Toripalimab and Lenvatinib With or Without Stereotactic Body Radiotherapy in Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT07922928
- Acronym / sponsor ID
- TL-SBRT-nccRCC / 2024-FXY-233-Urology
- Keywords
- Non-clear cell renal cell carcinoma; Neoadjuvant therapy; Toripalimab; Lenvatinib; Stereotactic body radiotherapy; Nephrectomy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 10 Nov 2026 (estimated)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 6 Nov 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.
This single-center, nonrandomized, two-cohort Phase II study will evaluate neoadjuvant toripalimab and lenvatinib with or without stereotactic body radiotherapy (SBRT) in patients with resectable, nonmetastatic locally advanced non-clear cell renal cell carcinoma. Approximately 36 participants will be enrolled. Both cohorts will receive six 21-day cycles of toripalimab and lenvatinib; one cohort will also receive SBRT to the primary renal tumor. Surgery is planned after neoadjuvant treatment. The primary outcome is the percentage of necrotic tumor cells in the resected tumor specimen.
Detailed description
Eligible participants with histologically confirmed, resectable, nonmetastatic locally advanced non-clear cell renal cell carcinoma will be enrolled into two nonrandomized cohorts. Cohort A will receive toripalimab 240 mg intravenously on day 1 of each 21-day cycle plus lenvatinib 12 mg orally once daily for six cycles. Cohort B will receive the same systemic treatment plus SBRT to the primary renal tumor at a total dose of 40 Gy in five fractions, delivered after completion of cycle 2 and before cycle 4. Tumor response will be assessed by imaging during and at the end of neoadjuvant treatment. Surgery will follow neoadjuvant treatment; the operating physician will determine the surgical approach based on imaging. Resected tumor specimens will be assessed for tumor cell necrosis and pathological response. Participants will be followed for recurrence, survival, and adverse events.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Toripalimab Plus Lenvatinib | Active comparator | Drug: Toripalimab, Drug: LenvatinibToripalimab 240 mg intravenously every 3 weeks plus lenvatinib 12 mg orally once daily for six 21-day cycles, followed by surgery. |
| Toripalimab Plus Lenvatinib and SBRT | Experimental | Drug: Toripalimab, Drug: Lenvatinib, Radiation: Stereotactic Body RadiotherapyToripalimab 240 mg intravenously every 3 weeks plus lenvatinib 12 mg orally once daily for six 21-day cycles. SBRT at 40 Gy in five fractions is delivered to the primary renal tumor after cycle 2 and before cycle 4, followed by surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Voluntary written informed consent.
- Age 18 years or older.
- ECOG performance status of 0 or 1 and life expectancy of at least 6 months.
- Histologically confirmed, resectable, nonmetastatic locally advanced non-clear cell renal cell carcinoma, excluding chromophobe and collecting duct carcinoma. Eligible disease includes T3aNxM0, T3bNxM0 without level III or IV venous tumor thrombus, T4NxM0, or TxN1M0.
- At least one measurable lesion according to RECIST version 1.1.
Key exclusion criteria (23 listed)
- Known hypersensitivity to toripalimab, lenvatinib, or their excipients.
- Chromophobe or collecting duct renal cell carcinoma.
- Anticancer monoclonal antibody or another investigational drug within 4 weeks before enrollment; prior PD-1/PD-L1-directed treatment for metastatic disease; or prior lenvatinib or another antiangiogenic drug.
- Distant organ metastasis or inability to undergo surgery.
- Systemic immunosuppressive treatment, including prednisone >10 mg/day or equivalent, within 2 weeks before enrollment.
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 |
|---|---|---|
| ToripalimabToripalimab 240 mg by intravenous infusion on day 1 of each 21-day cycle for six cycles. | Drug | Toripalimab Plus Lenvatinib, Toripalimab Plus Lenvatinib and SBRT |
| LenvatinibLenvatinib 12 mg orally once daily during six 21-day cycles of neoadjuvant treatment. | Drug | Toripalimab Plus Lenvatinib, Toripalimab Plus Lenvatinib and SBRT |
| Stereotactic Body RadiotherapySBRT to the primary renal tumor, 40 Gy in five fractions, after cycle 2 and before cycle 4. | Radiation | Toripalimab Plus Lenvatinib and SBRT |
Primary outcome
Tumor Cell Necrosis Rate (TCNR)
Time frame: At surgery following neoadjuvant treatment, approximately 5 to 6 months after the first dose.
Percentage of necrotic tumor cells in the resected tumor specimen, calculated from prespecified multisite pathological sampling.
4 secondary outcomes
R0 Resection Rate
Time frame: At surgery following neoadjuvant treatment, approximately 5 to 6 months after the first dose.
Objective Response Rate (ORR)
Time frame: From baseline through the final preoperative tumor assessment, approximately 18 weeks.
Disease Control Rate (DCR)
Time frame: From baseline through the final preoperative tumor assessment, approximately 18 weeks.
Major Pathological Response (MPR) Rate
Time frame: At surgery following neoadjuvant treatment, approximately 5 to 6 months after the first dose.
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 6 Nov 2026.
- Individual participant dataSharing planned: No. Individual participant data will not be shared because this small study collects sensitive clinical, imaging, and molecular data that could increase the risk of participant re-identification. Study results will be reported in aggregate form.
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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Toripalimab, Lenvatinib and Stereotactic Body Radiotherapy in people with Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma, run by Sun Yat-sen 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 8 inclusion and 23 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 6 Nov 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 Yulu Peng (02087342318, pengyl1@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor Cell Necrosis Rate (TCNR) (time frame: At surgery following neoadjuvant treatment, approximately 5 to 6 months after the first dose.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Nov 2026.