Study on MRD Prediction of Efficacy of Toripalimab in the Treatment of High-risk Recurrent Renal Carcinoma

Official title

Predictive Value of Minimal Residual Disease for Efficacy of Toripalimab in High-risk Recurrent Renal Cell Carcinoma Following Nephrectomy: A Prospective Single-arm Study

Overview

This is a prospective cohort study aimed at clarifying the predictive value of MRD for postoperative DFS and OS in high-risk recurrent renal cell carcinoma patients who have undergone radical nephrectomy and received adjuvant treatment with Toripalimab. Further differentiating patients who need adjuvant immunotherapy.

Detailed description

The study population is high-risk recurrent renal cell carcinoma patients who have undergone radical nephrectomy and meet the criteria of ECOG Score 0-1, no residual tumor on imaging. The study subjects will undergo MRD testing about 3 weeks after surgery, and the drug will be started within 4 weeks of surgery. Imaging (CT, MRI) will be performed from the first dose of Toripalimab, every 12 weeks, and DFS will be evaluated. Survival will be recorded every 3 months. The study aims to investigate the predictive value of MRD technology for DFS and OS in these patients after surgery and provide reference for distinguishing patients who need adjuvant immunotherapy.

Interventions

• Drug Toripalimab
  Toripalimab is a newly developed recombinant humanized (with a degree of 97%) anti-PD-1 monoclonal antibody (Chinese patent authorization number CN104250302B, PCT patent publication number (WO2014/206107A1)), belonging to the human IgG4/Kappa subtype. A point mutation of proline (S228P) has been introduced at the serine protein site 228 in the IgG4 hinge region to increase antibody stability and reduce possible IgG4 Fab chain substitutions. It can specifically bind to PD-1 and effectively block

Primary outcome measures

• Effect on the disease-free survival in the trial patients. [Time frame: Imaging (CT, MRI) was evaluated at 12 weeks after the first dose of Toripalimab and every 12 weeks. Until the tumor recurred or could not tolerate the side effects or the drug for 1 year.]

Secondary outcome measures (1)

• Effect on the overall survival in the trial patients. [Time frame: Imaging (CT, MRI) was evaluated 12 weeks after initial dosing and every 12 weeks until the tumor recurred or could not tolerate side effects or drugs for 1 year, and survival was recorded every 3 months.]

Eligibility criteria

• There must be a histological diagnosis of renal cell carcinoma, with or without sarcomatoid features of clear cell components.
• On the day of signing the informed consent form, both males and females must be at least 18 years old.
• The participants provide written informed consent for the trial before enrollment.
• Have high risk or M1 NED renal cell carcinoma as defined by the following pathological tumor-node-metastasis and Fuhrman grading status.

• High risk RCC

• pT4, Any Gr. N0, M0
• pT Any stage, Any Gr., N+, M0
• M1 NED RCC (participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at the time of nephrectomy)
• No previous systemic treatment for advanced RCC (except nephrectomy or pyelectomy) has been performed.
• Radical nephrectomy (and complete resection of metastatic lesions in M1 NED participants) was performed with a negative surgical margin.
• It must be evaluated by the investigator as tumor-free and verified by imaging such as CT or MRI. No suspicious brain metastases.
• Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
• Non-surgical sterilization or female participants of childbearing potential who are required to use a medically approved contraceptive method (such as an IUD, contraceptive pill or condom) during the study treatment period and for 3 months after the end of the study treatment period; Serum or urine HCG tests must be negative for women of non-surgical sterilization or childbearing age within 7 days prior to study enrollment; And must be non-lactation period; Non-surgical sterilization or male patients of childbearing age who consent to use a medically approved contraceptive method with their spouse during the study treatment period and for 3 months after the end of the study treatment period.
• Vital organ function meets the following requirements (excluding use of any blood components and cell growth factors within 14 days) : normal bone marrow reserve function; Absolute neutrophil count (ANC)≥1500/µL, Platelets≥100 000/µL, Hemoglobin ≥5.6 mmol/L (9g/dL); Normal renal function or serum creatinine ≤1.5 mg/d and/or creatinine clearance ≥30 mL/min for participants with creatinine levels \>1.5×institutional ULN; Normal liver function or Total bilirubin ≤1.5xULN, or direct bilirubin≤ULN for participants with total bilirubin levels \>1.5×ULN; AST (SGOT) and ALT (SGPT) ≤2.5×ULN; International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Changyi Quan — Tianjin

Identifiers

NCT: NCT07657325 · MRD-RCC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗