Perioperative TORIPALIMAB Plus LENVATINIB in Patients With Renal Cell Carcinoma Undergoing Nephrectomy (PLUTO)

NCT06114940 | Terminated Phase 2 FDA Drug

• 1 other identifier: 2025DZKY-005-02
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The PLUTO-trial is a single-center, open-label, phase II trial investigating Toripalimab plus Lenvatinib in patients with multi-stage clear-cell renal cell carcinoma. In this trial, patients will be enrolled in one of three cohorts according to the stage of their clear-cell renal-cell carcinoma: localized, locally advanced and metastatic RCC. Patients in all cohorts will receive four to five cycles of preoperative Toripalimab (240mg Q3W IV) plus Lenvatinib (20mg QD PO) and will undergo nephrectomy within four weeks after the last cycle. Patients in cohort 1 who are considered to be at high risk according to pathology results of surgery specimen, and all the patients in cohort 2 are supposed to receive postoperative doses of Toripalimab (240mg Q3W IV) for at most 17 doses. Patients in cohort 3 are supposed to continue Toripalimab plus Lenvatinib after surgery. The primary clinical endpoint of the study is immune-related pathological response to tumorigenesis, defined as the extent of tumor cell reduction in the tumor bed. Simon's two-stage design is used in this study. An initial cohort of 12 patients per cohort will be recruited, followed by an interim analysis. Recruitment to each cohort will be closed if a qualifying immune-related pathological response is not observed in any patient at an interim analysis. If qualifying immune-related pathological response is observed in at least one patient, additional 9 patients will be recruited in the cohort to 21 patients. Considering potential 10% dropout rate in the trial, an anticipation of 69 patients will be recruited for this study.

Conditions

Renal Cell Carcinoma (RCC)

Keywords

ccRCC; Perioperative therapy; Immunotherapy; Tyrosine Kinase Inhibitors; nephrectomy

Outcome Measures

Primary Outcomes (1)

• Immune-related pathologic reponse rate (irPR）

  IrPR is defined as the proportion of patients achieving a complete pathologic or major pathologic response. Complete or major pathological response are assessed according to the proportion of viable residual tumor in the initial tumor bed of HE sections from tumor tissue. Complete pathological response means no viable residue tumor in the initial tumor bed, and major pathological response with a ≤10% viable residue tumor in the initial tumor bed.

  Date of surgery

Secondary Outcomes (7)

• Adverse events

  From first dose to 28 days after last dose

• Surgical morbidity

  From date of surgery up to 28 days after surgery

• Objective response rate (ORR)

  Baseline to date of surgery

• Imaging density changes of lesions

  Baseline to date of surgery

• Down-staging rate of primary tumor T staging

  Baseline to date of surgery

Other Outcomes (1)

• Peripheral plasma and tissue-based biomarker analysis

  Up to 2 years after start of treatment

Study Arms (1)

Toripalimab + Lenvatinib followed by nephrectomy

EXPERIMENTAL

After 4-5 cycles of preoperative therapy, patients will undergo nephrectomy within 4 weeks. Patients with WHO/ISUP grading 4 RCC in cohort 1, and all patients of cohort 2 and 3 will receive postoperative dosing within 4 weeks for at most 17 doses. Subsequent follow-up will then be completed to assess adverse events and long-term outcomes. Cohort 1: Localized RCC (cT1b-T2bN0M0). Nephrectomy following preoperative therapy. For patients with WHO/ISUP grading 4 RCC in the resected tumor, postoperative dosing of Toripalimab beginning within 4 weeks after surgery for at most 17 doses. Cohort 2: Locally advanced RCC (cT3-4N0M0 or cTanyN1M0). Nephrectomy following preoperative therapy. Postoperative dosing of Toripalimab beginning within 4 weeks after surgery for at most 17 doses. Cohort 3: Metastatic RCC (cTanyNanyM1). Cytoreductive nephrectomy following preoperative therapy. Postoperative dosing of Toripalimab plus Lenvatinib beginning within 4 weeks after surgery for at most 17 doses.

Drug: Toripalimab; Drug: Lenvatinib

Interventions

Toripalimab DRUG

Preoperative: Toripalimab 240mg, IV on day 1 in a 3-week cycle. Preoperative Toripalimab contains 4-5 cycles. Postoperative: Toripalimab 240mg, IV on day 1 of a 3-week cycle. Postoperative Toripalimab following surgery within 4 weeks for patients mentioned above in cohort 1, 2 and 3.

Also known as: anti-PD-1 monoclonal antibody

Toripalimab + Lenvatinib followed by nephrectomy

Lenvatinib DRUG

Preoperative: Lenvatinib 20 mg orally, QD in a 3-week cycle. Preoperative Lenvatinib contains 4-5 cycles. Postoperative: Lenvatinib 20 mg orally, QD in a 3-week cycle. Postoperative Lenvatinib following surgery within 4 weeks for patients in cohort 3. Adjustment of dose: For patients with intolerable adverse reactions (CTCAE v5.0 grade 3 or grater), the dose could be reduced to 12mg for those who were suitable to continue taking the drug after systematic evaluation by the investigator. Patients who are assessed as intolerable and not suitable for continued medication will discontinue and undergo nephrectomy within 4 weeks.

Also known as: Lenvatinib mesylate (USAN), E7080, ER-203492-00, Multi-Kinase Inhibitor E7080

Toripalimab + Lenvatinib followed by nephrectomy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have fully understood and voluntarily signed the informed consent Form (ICF);
• Age: 18-80 years old (at the time of signing the informed consent); Both male and female; ECOG PS score: 0-1;
• RCC with clear cell component confirmed by histology or cytopathology, including locally advanced RCC with clear cell component;
• ECOG 0-1 points
• T1b-T2bN0M0, T3a-4N0M0, TanyN1M0 or M1RCC diagnosed by imaging at initial diagnosis:
• Cohort 1: T1b-T2bN0M0 RCC;
• Cohort 2: T3a-4N0M0 or TanyN1M0 RCC;
• Cohort 3: M1 RCC undergoing cytoreductive nephrectomy.
• Radical nephrectomy or partial nephrectomy or renal tumor enucleation was decided after the clinician made the treatment plan and communicated with the patient;
• Willingness and ability to comply with planned visits, therapeutic laboratory testing, and other procedures.

You may not qualify if:

• Signs of tumor metastasis involving the central nervous system;
• History of malignant tumors other than the study disease 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 had received other systemic treatment drugs, including targeted drugs, immunotherapy drugs and their combination regimens, or local anti-tumor therapy, or received investigational drugs or device therapy;
• Underwent major surgery (judged by the investigator) within 4 weeks before the first trial dose, were recovering, or were 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:
• Grade 2-4 immune myocarditis;
• Severe grade 4 proteinuria;
• Severe or life-threatening grade 4 immune hepatitis;
• Severe grade 3-4 immune pneumonitis;
• Severe inflammatory arthritis that significantly affects daily life or quality of life;
• Severe neurological toxicity:
• Myasthenia gravis grade 2-4;
• Guillain-Barre syndrome (GBS) or transverse myelitis of any grade;
• Grade 2-4 encephalitis;

Sponsors & Collaborators

• Jinling Hospital, China: lead

Study Sites (1)

Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China

Nanjing, Jiangsu, 210000, China

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

toripalimab; spartalizumab; lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate chief urologist

Study Record Dates

• First Submitted: September 3, 2023
• First Posted: November 2, 2023
• Study Start: December 20, 2022
• Primary Completion: January 10, 2026
• Study Completion: January 10, 2026
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

CN (1)