This prospective, open-label, single-arm Phase 2 study is evaluating toripalimab plus axitinib as induction therapy for adults with newly diagnosed metastatic clear cell renal cell carcinoma whose primary kidney tumor remains in place and whose baseline kidney-tumor core biopsy contains a biopsy-detectable tertiary lymphoid structure (TLS). TLS are organized immune-cell structures that may reflect an active anti-tumor immune environment.
Participants will receive approximately 12 weeks of toripalimab 240 mg by intravenous infusion every 3 weeks together with axitinib 5 mg by mouth twice daily. At Week 12, an independent multidisciplinary team will review treatment response, performance status, surgical risk, primary-tumor burden, metastatic burden, and the participant's preference to determine whether deferred cytoreductive nephrectomy is clinically appropriate. Surgery is not mandatory, and participants who do not undergo surgery will remain in the study's clinical follow-up cohort.
For participants who undergo deferred cytoreductive nephrectomy and still have at least one measurable metastatic lesion that has not been locally treated, the main clinical outcome is the proportion who are alive and free from disease progression 24 weeks after surgery. The study will also investigate whether the functional state of TLS in the treated primary kidney tumor and the persistence of TLS-associated T-cell and B-cell clones in blood after surgery are associated with longer control of remaining metastatic disease. Translational analyses may include pathology, multiplex immunofluorescence, T-cell and B-cell receptor sequencing, single-cell or single-nucleus sequencing, spatial transcriptomics, and serial blood sampling.
Age ≥18 years; able to understand the study and provide written informed consent before any study-specific procedure.
Newly diagnosed and previously untreated with systemic anticancer therapy for advanced renal cell carcinoma; the primary renal tumor remains in situ.
Histologically confirmed renal cell carcinoma containing a clear-cell component. Tissue used for diagnosis and TLS screening must be obtained from a core-needle biopsy of the primary renal tumor.
Clinical Stage IV disease according to the AJCC 8th edition, with synchronous distant metastasis confirmed radiologically or pathologically.
Prior systemic treatment for advanced renal cell carcinoma with an immune checkpoint inhibitor, VEGF/VEGFR-targeted therapy, mTOR inhibitor, chemotherapy, or other systemic anticancer therapy.
An urgent clinical indication for immediate surgery or local intervention because of uncontrolled bleeding, infection, urinary obstruction, pain, renal-function crisis, or another emergency that prevents safe completion of induction systemic therapy.
A rapidly life-threatening metastatic lesion that, in the investigator's judgment, requires immediate radiotherapy, surgery, or another local treatment before study therapy.
Active central nervous system metastases causing unstable symptoms. Participants with previously locally treated and stable CNS disease who are off corticosteroids or receiving a stable low physiologic/low dose may be considered individually by the MDT.