PLUTO: a Pilot Phase II Study of Perioperative TORIPALIMAB Plus LENVATINIB in Patients with Renal Cell Carcinoma Undergoing Nephrectomy
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 five 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, an additional patients will be recruited in the cohort to 18 patients. A maximum of 54 patients will be recruited for this study.
• 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.