Renal cell carcinoma
Conditions
Interventions
Combined therapy group:Iparolimab and Tuvonralimab (QL1706) Combined with Lenvatinib
Sponsors
The Third Medical Centre, Chinese PLA General Hospital, Beijing, China
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Patients must be aged 18 years or older at the time of consent. 2. Patients must have histopathological confirmation of renal cell carcinoma (RCC), including non-clear cell RCC as determined by initial IHC screening. For mixed histologies, the non-clear cell component must represent at least 50%. For patients diagnosed at outside institutions, tumor tissue (archival FFPE specimens or recently obtained samples) must be submitted to the Pathology Department of the Chinese PLA General Hospital for diagnostic confirmation. 3. Patients must have unresectable or advanced non-clear cell RCC (T3b–4NxMx, TxN1Mx, or TxNxM1) with radiographic or pathological evidence of distant metastasis. At least one measurable lesion, as defined by RECIST v1.1, must be present, and this lesion must either be untreated or must have demonstrated unequivocal progression following prior local therapy. 4. Patients must not have received prior systemic therapy for RCC, including cytokines, targeted agents, or investigational drugs. Patients who have received targeted monotherapy are eligible if treatment was limited to NCCN 2025 guideline–recommended first-line targeted agents, the treatment duration did not exceed one month, and an appropriate washout period has been completed. 5. Patients must have a life expectancy of more than 3 months. 6. Patients must have an adequate performance status, defined as a Karnofsky Performance Status (KPS) score greater than 70% or an ECOG performance status score of 0 or 1. 7. Patients must provide written informed consent and be able to comply with all protocol-specified visits, treatment schedules, and procedures. 8. Patients must agree to provide tumor tissue, blood, urine, stool, and other biological specimens as required by the study, and consent to their use for related research purposes. 9. Patients must have adequate hematologic, hepatic, and renal function, defined as follows: Absolute neutrophil count (ANC) >= 1.0 × 10^9/L, platelet count (PLT) >= 50 × 10^9/L, and hemoglobin (HGB) >= 80 g/L; Total bilirubin (TBIL) = 20 g/L; Serum creatinine (Cr) <= 3 × ULN.
Exclusion criteria
Exclusion criteria: 1. Patients who have received prior treatment with anti–PD-1, anti–PD-L1, anti–PD-L2 antibodies, anti–CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. 2. Patients with active brain metastases. 3. Patients with a history of a second primary malignancy within the past 2 years, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. Any second malignancy must be of a different origin or histology from the cancer under investigation in this study. 4. Patients who have undergone major surgery or experienced severe trauma within 4 weeks prior to enrollment. 5. Patients who require systemic glucocorticoid therapy exceeding 10 mg/day of prednisone (or equivalent) or other immunosuppressive drugs within 14 days before the first dose of study treatment. The use of topical, ocular, intra-articular, intranasal, or inhaled corticosteroids, as well as adrenal replacement therapy (>10 mg/day prednisone equivalent), is permitted in the absence of active autoimmune disease. 6. Patients with a known or suspected active autoimmune disease (congenital or acquired), such as interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, or thyroiditis. Patients with type 1 diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, skin disorders not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia), or conditions not expected to recur in the absence of an external trigger may be eligible. 7. Patients with a history of allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation will be excluded. 8. Patients with a known allergy to any component of monoclonal antibodies. 9. Patients with other uncontrolled or serious illnesses, including but not limited to the following: (1) Poorly controlled or severe active infections; (2) HIV infection (positive HIV antibody test); (3) Acute or chronic active hepatitis B (HBsAg positive and HBV DNA > 1 × 10³ copies/mL) or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA > 15 IU/mL); (4) Active tuberculosis. 10. Patients with New York Heart Association (NYHA) Class III–IV congestive heart failure or poorly controlled, clinically significant arrhythmia. 11. Patients with uncontrolled hypertension, defined as systolic blood pressure >= 160 mmHg or diastolic blood pressure >= 100 mmHg. 12. Patients with a history of arterial thrombotic, embolic, or ischemic events within 6 months prior to enrollment, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack. 13. Patients requiring anticoagulation therapy with warfarin (coumadin). 14. Patients with uncontrolled hypercalcemia, defined as ionized calcium > 1.5 mmol/L, total calcium > 12 mg/dL, or corrected serum calcium above the upper limit of normal (ULN), or symptomatic hypercalcemia requiring ongoing bisphosphonate therapy. 15. Patients with any other acute or chronic medical condition, psychiatric disorder, or abnormal laboratory finding that, in the judgment of the investigator, may increase the risks associated with study participation or administration of the study drug, interfere with the interpretation of study results, or otherwise render the patient unsuitable for participation. 16. Pregnant or breastfeeding women. 17. Patient
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate, ORR;Progression-Free Survival, PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease Control Rate, DCR;Time to Progression, TTP;Overall Survival, OS; | — |
Countries
China
Contacts
Public ContactGu Liangyou
The Third Medical Centre, Chinese PLA General Hospital, Beijing 100039, China.
Outcome results
None listed