Primary Disease: Unresectable or Metastatic Renal Cell Carcinoma Focus of the Study:PFS Assessed by IRC Per RECIST 1.1
Conditions
Brief summary
This is a randomized, open-label, controlled, multicenter, phase III trial to compare the efficacy and safety of Toripalimab in combination with axitinib to sunitinib monotherapy as a first-line therapy for advanced RCC. Eligible patients will be randomized 1:1 to receive the combination therapy of Toripalimab and axitinib or sunitinib monotherapy.
Interventions
COMBINATION_PRODUCTBiological : Toripalimab Drug: Axitinib
Biological: Toripalimab, Intravenous infusion Drug: Axitinib, oral tablet
DRUGsunitinib
Drug: Sunitinib, oral capsule
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Fully understand and be willing to provide written informed consent. 2. Male or female with age ≥ 18 years and \<80 years. 3. Have received no prior systemic therapy after previous metastasis for RCC, histologically confirmed diagnosis of unresectable, recurrent or metastatic RCC with clear cell component with or without sarcomatoid features,Prior cytokine therapy was allowed. 4. The IDMC score was medium to high risk. 5. Having at least one measurable disease per RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if re-progression has been demonstrated. 6. Provide archival tumor tissues or newly obtained biopsies if patients participate in the exploratory study. 7. ECOG PS 0 or 1. 8. Adequate function of vital organs: Bone marrow function (without blood or blood products transfusion, without hematopoietic stimulating factor or other medication to improve blood cell count within 2 days prior to first dose of study drug): Absolute neutrophil count (ANC) ≥ 1.5×109/L. Platelets ≥ 100×109/L. Hemoglobin ≥ 9.0g/dL or ≥ 5.6mmol/L. Renal function: Serum creatinine ≤ 1.5×ULN Hepatic function: Serum total bilirubin ≤1.5×ULN or total bilirubin levels \>1.5×ULN with direct bilirubin ≤ ULN. AST and ALT ≤2.5 × ULN, ≤5×ULN in those with hepatic metastasis. Endocrine function: Normal thyroid stimulating hormone, or abnormal TSH whilst normal FT3 and FT4. Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN, and activated partial thromboplastin time (aPTT) ≤1.5×ULN, Subjects receiving anticoagulant therapy (e.g., heparin or warfarin) may participate in the study with PT or aPTT levels within the scope of the proposed therapy and monitored during study treatment.Left ventricular ejection fraction (LVEF) ≥ 50%. 8\. Being willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. 10\. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first treatment dose. Female subjects of childbearing potential and male subjects whose partners are of childbearing potential must agree to use a highly effective methods of contraceptive throughout the study and for 180 days after the last dose of study therapy.
Exclusion criteria
Bone marrow functiPatients with any of the following conditions will not be included in the study: 1. PriorAnti-PD-1, PD-L1 or CTLA-4 agents ). 2. Prior systemic anti-cancer therapy after metastasis (e.g., VEGF/VEGFR or mTOR targeting agents, including (but not limited to) sunitinib, axitinib, sorafenib, pazopanib, cabozantinib, lenvatinib, bevacizumab or everolimus. 3. Progression or recurrence during neoadjuvant/adjuvant therapy for renal cell cancer or within 12 months after the last dose treatment. 4. Has participated or is currently participating in a trial of investigational agent within 4 weeks prior to the first dose of study treatment, unless observational (non-interventional) clinical study or follow-up period of interventional study. 5. Had major surgery (judged by investigators) within 4 weeks prior to the first dose of study treatment or has not recovered from prior surgery. 6. Has traditional Chinese medicine or Chinese patent medicine preparation with anti-cancer indication within 2 weeks prior to the first dose of study treatment. 7. Requiring corticosteroids (Prednisone \>10 mg/day or equivalent analogue) or other immunosuppressive agents within 2 weeks prior to the first dose of study treatment. Patients without active autoimmune disease using inhaled prednisone \>10 mg/day will not be excluded from the study. 8. Has a history of organ transplantation or required long-term treatment with corticosteroids. 9. Hypothyroidism, hypoadrenalism or hypopituitarism that can be controlled only with hormone replacement therapy, type I diabetes, psoriasis or leucoderma not requiring systematic treatment. 10. Not recovered from the toxicity of prior anti-cancer therapy, i.e., not recovered to baseline, Grade 0-1 (NCI-CTCAE 5.0, except alopecia) or per inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS assessed by IRC per RECIST 1.1. | 3 years | To compare the progression-free survival (PFS) per response evaluation criteria in solid tumors (RECIST) 1.1 as assessed by independent review committee (IRC) in subjects treated with Toripalimab plus axitinib vesus sunitinib monotherapy as a first-line treatment for advanced RCC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS assessed by investigators per RECIST 1.1; | 3 years | The treatment effect of with Toripalimab plus axitinib vesus sunitinib monotherapy, will be assessed using RECIST 1.1 to determine tumor response; |
| ORR assessed by investigators and IRC per RECIST 1.1, respectively; | 3 years | The treatment effect of with Toripalimab plus axitinib vesus sunitinib monotherapy, will be assessed using IRC and RECIST 1.1 to determine tumor response; |
| DOR, assessed by investigators and IRC per RECIST 1.1, respectively; | 3 years | The treatment effect of with Toripalimab plus axitinib vesus sunitinib monotherapy, will be assessed using IRC and RECIST 1.1 to determine tumor response; |
| DCR assessed by investigators and IRC per RECIST 1.1, respectively; | 3 years | The treatment effect of with Toripalimab plus axitinib vesus sunitinib monotherapy, will be assessed using IRC and RECIST 1.1 to determine tumor response; |
| OS assessed by investigators and IRC per RECIST 1.1, respectively; | 3 years | The treatment effect of with Toripalimab plus axitinib vesus sunitinib monotherapy, will be assessed using IRC and RECIST 1.1 to determine tumor response; |
| Incidence and grade of AEs and SAEs per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, incidence of ≥ grade 3 AE; | 3 years | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |
| Incidence and grade of AEs and SAEs related to study drugs per NCI-CTCAE version 5.0, AEs ≥ grade 3 related to the study drugs. | 3 years | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |
| overall survival rate assessed by investigators and IRC per RECIST 1.1, respectively; | 3 years | The treatment effect of with Toripalimab plus axitinib vesus sunitinib monotherapy, will be assessed using IRC and RECIST 1.1 to determine tumor response; |
Other
| Measure | Time frame | Description |
|---|---|---|
| Biomarker | 2 years | Correlation between biomarker (PD-L1) and the efficacy of Toripalimab |
Countries
China
Outcome results
None listed