None listed
Conditions
Interventions
Drug : In this study, treatment consists of a neoadjuvant and an adjuvant phase, during which Zanzalintinib and Pembrolizumab are administered. Patients will receive a total of 6 cycles (21 days per c
Sponsors
Yonsei University Health System, Severance Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1) Subjects with clear cell renal cell carcinoma (clear cell RCC) confirmed by pathological or cytological diagnosis. meeting one or more of the following criteria: ? Locally advanced disease or resectable metastatic disease. ? Resectable intermediate- to high-risk or high-risk patients are eligible for enrollment. ? Resectability is determined by multidisciplinary Resectability will be determined based on multidisciplinary evaluation. Resectable metastatic disease is defined as cases in which, in the presence of a primary tumor, complete resection of both the primary tumor and all identifiable metastatic lesions is deemed feasible by multidisciplinary assessment. All metastatic lesions must be amenable to complete resection within the planned surgical schedule. Subjects will be excluded from enrollment if metastatic lesions have already been completely resected prior to study entry, are deemed unresectable, or are expected to have residual disease after attempted resection. Intermediate-High Risk Group cT2· Grade 4· or· Sarcomatoid cT3, any Grade, N0 High Risk Group cT4, any Grade, N0 any cT, any Grade, N+ Resectable Metastatic Disease any cT, any cN, any Grade, M1 (2) Age 19 years or older on the day of consent (3) ECOG performance status 0~1 (4) Female subjects of childbearing potential must have a negative result on a serum or urine pregnancy test conducted during the clinical trial screening period. If the urine test result is positive or cannot be confirmed as negative, a serum pregnancy test must be performed. (5) Sexually active fertile subjects and their partners must agree to use highly effective method of contraception (defined in Appendix E) during the course of the study and for a specified period after the last dose of treatment, as defined below. Subjects and their partners must consistently use highly effective contraception, and an additional contraceptive method (e.g., condom) is required. • Male subjects: Must use a condom during the treatment period and for 120 days after the last dose and must agree not to donate sperm during this period. • Female subjects: Women of childbearing potential (WOCBP) must comply with protocol-specified contraceptive methods during the treatment period and for 186 days after the last dose. The durations reflect the longer washout period between Zanzalintinib and Pembrolizumab. (6) Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 as determined by the Investigator. (7) Adequate organ and marrow function as defined by the table below. Table 2. Organ function requirements for eligibility evaluation Organ System Laboratory Test Criteria Hematological Absolute neutrophil count (ANC) =1,500/µL Platelets =100,000/µL Hemoglobin =9.0 g/dL or =5.6 mmol/L Renal Creatinine OR creatinine clearance (CrCl) (If CrCl is used, estimated GFR may also be acceptable) =1.5 × ULN OR for subjects with creatinine>1.5 × ULN , CrCl =40 mL/min Urine protein-to-creatinine ratio (UPCR) =1.5 mg/mg Hepatic Total bilirubin =1.5 × ULN OR, For subjects with total bilirubin>1.5 × ULN, direct bilirubin=ULN (For subject with known Gilbert’s syndrome, as an exception: total bilirubin <3 × ULN and ALT <3 × ULN) AST (SGOT) and ALT (SGPT) =2.5 × ULN (or =5 × ULN for subjects with liver metastasis) Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) =1.5 × ULN, or if the subject is receiving anticoagulant ther
Exclusion criteria
Exclusion criteria: (1) Concurrent anticancer treatments other than the investigational therapy, including chemotherapy, curative radiotherapy, surgery, immunotherapy, biological therapy, or tumor embolization. (2) Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible. (3) Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. (4) History of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2 therapies, or vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors. (5) Any complementary medicine within 2 weeks prior to first dose of treatment. (6) History of another malignancy within the 2 years prior to the first dose of study treatment, except for basal cell carcinoma or squamous cell carcinoma treated solely by local excision, cervical carcinoma in situ, or completely resected papillary thyroid carcinoma. (7) Diagnosis of immunodeficiency or is receiving systemic steroid therapy (> 10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment. Inhaled, intranasal, intraarticular, and topical corticosteroids and mineralocorticoids are allowed (8) Presence of untreated fistulas, irrespective of cancer status. (9) Presence of uncontrolled concomitant diseases, including but not limited to ongoing or active infections, symptomatic congestive heart failure, unstable angina, cardiac arrhythmias, immunosuppressive conditions, autoimmune diseases, underlying pulmonary disorders, or psychiatric or social conditions that may limit compliance with clinical trial requirements. (10) Active autoimmune diseases requiring systemic treatment (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years before the treatment of trial. Physiologic corticosteroid replacement for thyroid hormone, insulin, or adrenal/pituitary insufficiency is excluded from this criterion. (11) Thrombotic, embolic, venous, or arterial events (e.g., cerebrovascular accident including transient ischemic attack, deep vein thrombosis, pulmonary embolism) within 6 months before the treatment of trial. (12) Concomitant anticoagulation with oral anticoagulants and platelet inhibitors. Only low-dose aspirin and LMWH are permitted. (13) Subjects must have discontinued anticoagulant within 3 days or 5 half-lives prior to the first dose of treatment (whichever is longer) (14) History of non-infectious pneumonitis requiring corticosteroid therapy or presence of current pneumonitis. (15) Uncontrolled hypertension (>140 mmHg systolic or >90 mmHg diastolic despite optimal antihypertensive treatment (16) Prior history of myocarditis (17) Known gastric or esophageal varices (18) Ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks (19) Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 tsp of red blood, or other history of significant bleeding within 12 weeks before first dose of study treatment (20) Symptomatic cavitating pulmonary lesion(s) or endobronchial disease (asymptomatic or radiated lesions allowed) (21) Lesions i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective response rate | — |
Secondary
| Measure | Time frame |
|---|---|
| safety and tolerability;major pathologic response;event-free survival, EFS;overall survival, OS;Surgery-related Endpoints(Surgery completion rate, Pathologic complete resection rate, Surgery delay rate, Reoperation rate, Postoperative complications, Surgery-related mortality) | — |
Countries
Korea, Republic of
Contacts
Public ContactSang Joon Shin
Yonsei University Health System, Severance Hospital
Outcome results
None listed