High-risk localized and locally advanced clear cell renal cell carcinoma (ccRCC)
Conditions
Interventions
Intervention group:Iparomlimab and Tuvonralimab in combination with Lenvatinib
Sponsors
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Ability to understand and agree to comply with the study requirements and assessment schedule, and voluntarily provide written informed consent (ICF) prior to any trial-related procedures. 2. Age >= 18 years and = 3 months. 8. At least one measurable lesion according to RECIST v1.1. 9. Planned to receive neoadjuvant therapy and surgical resection. 10. Adequate major organ function within 7 days prior to treatment, meeting the following criteria: (1) Hematology: absolute neutrophil count >= 1.5 x 10^9/L; hemoglobin >= 80 g/L; platelet count >= 90 x 10^9/L. (2) Blood biochemistry: total bilirubin = 50 mL/min. (3) Left ventricular ejection fraction >= 50%. (4) Activated partial thromboplastin time (APTT), international normalized ratio (INR), and prothrombin time (PT) <= 1.5 x ULN. (5) Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects with total T3 (or free T3) and free T4 within the normal range are also eligible. (6) Cardiac enzymes and troponin within normal limits (isolated laboratory abnormalities deemed clinically insignificant by the investigator are also allowed). 11. Female subjects of childbearing potential must agree to use effective contraception (e.g., intrauterine device, contraceptive pill, or condom) during the study and for 6 months after study completion; serum pregnancy test must be negative within 72 hours prior to the first dose, and they must not be breastfeeding. Male subjects must agree to use effective contraception during the study and for 6 months after study completion.
Exclusion criteria
Exclusion criteria: 1.Presence of symptomatic or untreated known brain metastases or other central nervous system (CNS) metastases. CNS metastases that have been completely resected and/or irradiated with documented stability or improvement are not exclusionary, provided that computed tomography (CT) shows stability for at least 4 weeks prior to screening, with no evidence of cerebral edema and no requirement for glucocorticoids or anticonvulsants; 2.Patients with advanced or metastatic renal cell carcinoma, or non-clear cell renal cell carcinoma; 3.Known hypersensitivity to the investigational product or any of its excipients; or previous allergy to Chinese hamster ovary cell products or other recombinant human or humanized antibodies. 4.Prior discontinuation of immunotherapy due to severe and/or life-threatening immune-related adverse events; 5.Adverse events from prior anti-tumor therapy have not recovered to = Grade 1 per NCI-CTCAE v5.0 at enrollment (except for alopecia or other toxicities deemed by the investigator to be tolerable and not clinically significant); 6.Presence of any active autoimmune disease or history of autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (patients on hormone replacement therapy may be considered for inclusion); patients with psoriasis or childhood asthma/allergy that has completely resolved and requires no intervention in adulthood may be considered, but those requiring bronchodilators for medical intervention are excluded; 7.History of immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation or allogeneic bone marrow transplantation. 8.Presence of poorly controlled cardiac symptoms or diseases, including but not limited to: heart failure = NYHA class II, unstable angina, myocardial infarction within 1 year, and clinically significant supraventricular or ventricular arrhythmias that have not been clinically intervened or remain poorly controlled after intervention; 9.Severe infection (CTCAE > Grade 2) within 4 weeks prior to the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, infectious complications, etc.; active pulmonary inflammation on baseline chest imaging; signs or symptoms of infection or need for oral or intravenous antibiotic therapy within 14 days prior to the first dose of study drug (prophylactic antibiotics are allowed). 10.Active pulmonary tuberculosis infection identified by history or CT, or history of active pulmonary tuberculosis infection within 1 year prior to enrollment, or history of active tuberculosis infection more than 1 year ago without adequate treatment. 11.Positive HBV DNA test; hepatitis C (positive anti-HCV antibody with HCV RNA above the lower limit of quantification of the assay). 12.Diagnosis of another malignancy within 5 years prior to the first dose of study drug, except for malignancies with low risk of metastasis or death, such as adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or cervical carcinoma in situ, which may be considered for enrollment. 13.Known hereditary or acquired bleeding or thrombotic tendency (e.g., hemophilia, coagulation disorders, thrombocytopenia, etc.), or currently receiving thrombolytic or anticoagulant therapy. 14.Clinically significant bleeding symptoms or clear bleeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate;12?month / 24?month DFS rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pathological Complete Response Rate;12?month / 24?month overall survival (OS) rate;Disease?Free Survival; | — |
Countries
China
Contacts
Public ContactHongqian Guo
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
Outcome results
None listed