TACTIC-RCC: Toripalimab Plus Axitinib Induction With Selective Deferred Cytoreductive Nephrectomy in TLS-Positive Advanced Clear Cell Renal Cell Carcinoma

Summary

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.

Conditions

• Metastatic Clear Cell Renal Cell Carcinoma
• Advanced Clear Cell Renal Cell Carcinoma

Interventions

DRUG

Toripalimab

Toripalimab 240 mg by intravenous infusion on Day 1 every 3 weeks, with four planned cycles during the approximately 12-week induction period. Dose reduction is not permitted. Treatment may be withheld or permanently discontinued for immune-related or other unacceptable toxicity. For participants without progression or unacceptable toxicity, toripalimab is generally resumed after adequate postoperative recovery (typically 2-6 weeks after surgery) or continued in non-surgical participants, for a total treatment duration of approximately 2 years.

DRUG

Axitinib

Axitinib 5 mg orally twice daily, administered continuously during induction. Routine dose escalation is not planned. For intolerance, axitinib may be interrupted and reduced stepwise to 3 mg twice daily and then 2 mg twice daily. For elective surgery, axitinib is stopped at least 2 days before surgery, with 3-5 days preferred depending on bleeding/thrombotic and surgical considerations, and is not restarted until at least 2 weeks after major surgery and adequate wound healing. After recovery, axitinib may continue until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision.

PROCEDURE

Deferred Cytoreductive Nephrectomy

Selective cytoreductive nephrectomy considered after approximately 12 weeks of induction therapy. Core conditions include clear clinical benefit or controlled systemic disease, ECOG 0-1, acceptable anesthetic/perioperative risk, technically resectable primary tumor, a meaningful clinical purpose for surgery, and informed participant preference after MDT discussion. Surgical approach (radical or partial nephrectomy; open, laparoscopic, or robotic; management of venous tumor thrombus and lymph nodes when indicated) is determined by the surgical MDT.

Sponsors & Collaborators

• Fudan University

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-20

Primary Completion

2027-12-31

Completion

2028-12-31