Ipilimumab N01 Plus Sintilimab and Lenvatinib as First-line Therapy for Locally Advanced or Metastatic TFE3-Rearranged Renal Cell Carcinoma: A Prospective, Multicenter, Single-Arm, Phase II Clinical Trial

NCT07715565 | Not Yet Recruiting Phase 2

• 1 other identifier: LIST
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II, multicenter, single-arm, open-label study evaluates first-line ipilimumab N01 plus sintilimab and lenvatinib in patients with locally advanced or metastatic TFE3-rearranged renal cell carcinoma (TFE3-rRCC), a rare subtype lacking established first-line systemic therapy. Eligible patients (age ≥14 years, ECOG ≤2, measurable disease per RECIST v1.1, no prior systemic therapy) will receive ipilimumab N01 1 mg/kg Q6W for 4 cycles, sintilimab 200 mg Q3W for up to 35 cycles, and lenvatinib 12 mg or 8 mg QD continuously. The primary endpoint is objective response rate (ORR) per RECIST v1.1. Secondary endpoints include disease control rate, duration of response, progression-free survival, overall survival, safety per NCI CTCAE v5.0, and quality of life. Exploratory biomarker analyses will assess potential predictors of treatment response.

Conditions

Renal Cell Carcinoma (Kidney Cancer); Immunotherapy; Molecular Targeted Therapy

Keywords

Sintilimab; ipilimumab; lenvatinib

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective response rate is the proportion of participates with complete response (CR) or partial response (PR), based on RECIST1.1.

  3 years

Secondary Outcomes (10)

• Adverse Events (AEs)

  3 years

• Overall Survival (OS)

  3 years

• Progression-Free Survival (PFS)

  3 years

• Disease Control Rate (DCR)

  3 years

• Duration of Response (DoR)

  3 years

Study Arms (1)

Combination treatment group

EXPERIMENTAL

Participants receive ipilimumab 1 mg/kg intravenously every 6 weeks for the first 4 cycles (induction phase) in combination with sintilimab 200 mg intravenously every 3 weeks for up to 35 cycles (approximately 2 years), plus lenvatinib 12 mg (body weight ≥60 kg) or 8 mg (body weight \<60 kg) orally once daily continuously until disease progression, unacceptable toxicity, or loss of clinical benefit.

Drug: Ipilimumab Injection; Drug: Sintilimab injection; Drug: Lenvatinib

Interventions

Ipilimumab Injection DRUG

A human monoclonal antibody targeting CTLA-4.

Also known as: Ipilimumab

Combination treatment group

Lenvatinib DRUG

A multi-target tyrosine kinase inhibitor (VEGFR1-3, FGFR1-4, PDGFRα, KIT, RET).

Combination treatment group

Sintilimab injection DRUG

Recombinant human-derived immunoglobulin G (IgG4)-type anti-programmed cell death receptor-1 (PD-1) monoclonal antibody, by binding to PD-1 and blocking PD-1 binding to PD-L1 and PD-L2, disarms the immunosuppressive effect, activates T-cell function, and enhances T-cell immunosurveillance and killing ability against tumors to generate tumor immune response.

Also known as: Sintilimab

Combination treatment group

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥14 years, any gender.
• Histologically confirmed locally advanced or metastatic TFE3-rearranged renal cell carcinoma (TFE3-rRCC) by FISH and/or next-generation sequencing.
• Stage IV disease per the 2017 8th edition TNM staging system.
• No prior systemic therapy with immune checkpoint inhibitors (PD-1/PD-L1 inhibitors) or targeted agents (TKI, mTORi); prior targeted therapy ≤1 month is allowed after an adequate washout (5.5 half-lives).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Life expectancy ≥3 months.
• Signed informed consent and ability to comply with study visits and procedures.
• Willingness to provide tumor tissue and blood specimens for correlative studies.
• Adequate organ and bone marrow function within 14 days prior to enrollment:
• Hematology: ANC ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥90 g/L. Hepatic: TBIL ≤1.5×ULN, ALT/AST ≤2.5×ULN, albumin ≥20 g/L. Renal: serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min.

You may not qualify if:

• Active central nervous system metastases.
• History of other malignancies within 3 years (different primary site or histology), except well-controlled basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma in situ.
• Major surgery or severe trauma within 4 weeks prior to enrollment.
• Systemic corticosteroids (\>10 mg/day prednisone equivalent) or other immunosuppressive agents within 14 days before first dose (topical, ophthalmic, intra-articular, intranasal, inhaled, or physiologic replacement steroids are permitted).
• Known or suspected active autoimmune disease (e.g., interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, thyroiditis), except type 1 diabetes, hypothyroidism requiring hormone replacement only, or skin conditions not requiring systemic treatment. Known allogeneic organ transplant (except corneal) or allogeneic hematopoietic stem cell transplant.
• Known hypersensitivity to ipilimumab N01, sintilimab, or lenvatinib.
• Uncontrolled severe comorbidities including:
• Active or poorly controlled severe infection. HIV infection. Active hepatitis B (HBsAg-positive and HBV DNA \>1×10³ IU/mL) or active hepatitis C (HCV antibody-positive and HCV RNA \>15 IU/mL).
• Active pulmonary tuberculosis. New York Heart Association Class III-IV congestive heart failure, symptomatic arrhythmia, uncontrolled atrial fibrillation, or left ventricular ejection fraction below the lower limit of normal.
• Uncontrolled arterial hypertension (systolic ≥160 mmHg or diastolic ≥100 mmHg). Arterial thrombosis, embolism, or ischemia within 6 months (e.g., myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack).
• Uncontrolled adrenal insufficiency. Severe, non-healing wounds or ulcers; gastrointestinal disorders impairing absorption; active uncontrolled bleeding or high bleeding risk (e.g., esophageal/gastric varices requiring intervention); or unstable anticoagulation with clinically significant bleeding.
• Any other acute or chronic medical or psychiatric condition, or laboratory abnormality, that in the opinion of the investigator increases the risk associated with study participation, may interfere with interpretation of study results, or makes the patient unsuitable for the study.
• Pregnant or lactating women.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital, Chengdu, Sichuan 610000

Chengdu, China

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

Ipilimumab; sintilimab; lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; 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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hao Zeng, Doctor

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hao Zeng, Doctor

CONTACT

+86-18980602129; kucaizeng@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 15, 2026
• First Posted: July 20, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: July 20, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Data would be available starting from the time when summary data are published or otherwise made available, for 3 years.
• Access Criteria: Other researchers access the data by sending an email to our PI.

Locations

CN (1)