Pucotenlimab, Lenvatinib, and SBRT Before Surgery for Localized Clear Cell Renal Cell Carcinoma (PLS-NEO-RCC)

November 2, 2026 updated by: ZHOU FANGJIAN, Sun Yat-sen University

A Single-Arm Phase II Study of Neoadjuvant Pucotenlimab, Lenvatinib, and Stereotactic Body Radiotherapy in Patients With Localized Clear Cell Renal Cell Carcinoma and High-Risk Partial Nephrectomy

This single-arm Phase II study will evaluate the efficacy and safety of neoadjuvant pucotenlimab, lenvatinib, and stereotactic body radiotherapy (SBRT) in adults with localized clear cell renal cell carcinoma who are candidates for partial nephrectomy but have tumors that make the operation technically difficult. Approximately 24 participants will receive up to six cycles of pucotenlimab with daily lenvatinib. SBRT will be delivered to the primary renal tumor during neoadjuvant treatment. Surgery is planned after neoadjuvant treatment. The primary outcome is objective response rate.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a prospective, single-arm Phase II study using a Simon optimal two-stage design. The study plans to enroll 24 participants. In stage 1, eight participants will be enrolled; if no more than three have an objective response, the study will stop for futility. Otherwise, 16 additional participants will be enrolled.

Participants will receive pucotenlimab 200 mg by intravenous infusion every 3 weeks for up to six cycles and lenvatinib 12 mg orally once daily during neoadjuvant treatment. SBRT will be delivered to the primary renal tumor at a total dose of 40 Gy in five fractions after completion of the second pucotenlimab cycle and before the fourth cycle. Tumor imaging will be performed during neoadjuvant treatment. Surgery, preferably partial nephrectomy when feasible, is planned 2 to 4 weeks after the sixth pucotenlimab cycle. Efficacy, surgical outcomes, and adverse events will be evaluated.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Voluntary written informed consent.
  • Age 18 years or older.
  • ECOG performance status of 0 or 1.
  • Life expectancy of at least 3 months.
  • Preoperative biopsy confirming clear cell renal cell carcinoma or renal cell carcinoma with a predominant clear cell component.
  • Willingness to undergo partial nephrectomy.
  • A localized renal tumor for which partial nephrectomy is indicated but technically difficult: a 4-7 cm hilar tumor; a 4-7 cm tumor that is at least 75% endophytic; or a tumor larger than 7 cm.
  • At least one measurable lesion suitable for repeated, accurate measurement.
  • Adequate organ function: absolute neutrophil count ≥1.5 × 10^9/L; platelet count ≥100 × 10^9/L; hemoglobin ≥90 g/L; total bilirubin ≤1.5 × upper limit of normal (ULN); ALT and AST ≤2.5 × ULN, or ≤5 × ULN for participants with liver metastases; albumin ≥28 g/L; INR and APTT ≤1.5 × ULN. No blood component transfusion or hematopoietic growth-factor support is permitted within 2 weeks before treatment.
  • Willingness and ability to comply with study visits, treatment, laboratory assessments, and other study requirements.

Exclusion Criteria:

  • Lymph node metastasis or metastatic renal cell carcinoma.
  • Tumor encasement of the renal artery, tumor thrombus in the renal vein, or diffuse tumor growth without a clear boundary from normal renal parenchyma.
  • Inability to tolerate general anesthesia according to the preoperative assessment.
  • Severe cardiovascular or cerebrovascular disease, or uncontrolled hypertension or diabetes.
  • Long-term immunosuppressive therapy after organ transplantation, or current use of immunosuppressive medication.
  • Active infection or fever.
  • T-cell lymphoma or multiple myeloma.
  • Concurrent malignancy, current treatment for another benign or malignant tumor, or a history of another malignancy within the previous 6 months.
  • Use of herbal medicines with an anticancer indication or systemic immunomodulatory agents, including thymosin, interferon, or interleukin, within 14 days before the first study treatment; local use to control pleural effusion is permitted.
  • Active or potentially recurrent autoimmune disease, except vitiligo, alopecia, psoriasis, or eczema not requiring systemic therapy; hypothyroidism due to autoimmune thyroiditis requiring only a stable dose of hormone replacement; or type 1 diabetes requiring only a stable dose of insulin.
  • Concurrent enrollment in another interventional clinical study, except participation in its follow-up period; participation in a noninterventional observational study is permitted.
  • Known psychiatric illness or a history of drug abuse, alcohol abuse, or illicit drug use.
  • Pregnancy or breastfeeding.
  • Any other disease, treatment, or laboratory abnormality that may confound the study results, prevent full participation, or make participation contrary to the participant's best interests.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Pucotenlimab Plus Lenvatinib and SBRT

Participants will receive neoadjuvant pucotenlimab 200 mg intravenously every 3 weeks for up to six cycles and lenvatinib 12 mg orally once daily. SBRT at 40 Gy in five fractions will be delivered to the primary renal tumor after cycle 2 and before cycle 4. Surgery is planned after neoadjuvant treatment, with partial nephrectomy preferred when feasible.
Drug: Pucotenlimab

200 mg administered by intravenous infusion once every 3 weeks for up to six cycles.

Drug: Lenvatinib

Lenvatinib 12 mg taken orally once daily during neoadjuvant treatment; treatment is stopped at least 3 days before surgery.

Radiation: Stereotactic Body Radiotherapy

SBRT to the primary renal tumor at a total dose of 40 Gy in five fractions, delivered after completion of pucotenlimab cycle 2 and before cycle 4.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: From baseline through completion of neoadjuvant treatment, approximately 18 weeks.

Percentage of participants with a complete response or partial response of the primary renal tumor according to RECIST version 1.1 during neoadjuvant treatment.
From baseline through completion of neoadjuvant treatment, approximately 18 weeks.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Major Pathological Response (MPR) Rate
Time Frame: At surgery, approximately 20 to 22 weeks after treatment initiation.

Percentage of participants with major pathological response in the resected primary tumor.
At surgery, approximately 20 to 22 weeks after treatment initiation.
Partial Nephrectomy Success Rate
Time Frame: At surgery, approximately 20 to 22 weeks after treatment initiation.

Percentage of participants who undergo partial nephrectomy after neoadjuvant treatment.
At surgery, approximately 20 to 22 weeks after treatment initiation.
R0 Resection Rate
Time Frame: At surgery, approximately 20 to 22 weeks after treatment initiation.

Percentage of surgically treated participants with microscopically negative surgical margins.
At surgery, approximately 20 to 22 weeks after treatment initiation.
Surgical Complications
Time Frame: From surgery through the 3-month postoperative visit.

Number and percentage of participants with surgical complications, including bleeding and urinary leakage.
From surgery through the 3-month postoperative visit.
Adverse Events
Time Frame: From informed consent through 30 days after the last dose of study medication.

Number and percentage of participants with adverse events, graded according to NCI-CTCAE version 4.0.
From informed consent through 30 days after the last dose of study medication.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 10, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 2, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 2, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 6, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 6, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2024-FXY-321-Urology
  • 2024-FXY-321-Urology (Other Identifier: Sun Yat-sen University cancer center)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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