First Line Randomised Study Platform to Optimize Treatment in Patients With Metastatic Renal Cell Carcinoma
Systemic therapy for renal cell carcinoma (RCC) relies on 2 classes of agents: anti-angiogenic targeted therapy (Vascular endothelial growth factor Tyrosine Kinase Inhibitor- VEGFR TKI) and immune checkpoint inhibitor (ICI), targeting either PD1/PDL1 axis or CTLA4. Combination therapy is SOC for clear cell RCC in all guidelines with either ICI-ICI or ICI-VEGFR TKI. However, no head-to-head comparison have been performed between the 2 approaches and patients are treated based on physician decision without clinical /biomarker factors to guide treatment selection. PDL1 staining is, to date, the biomarker that has demonstrated its ability to enrich for overall survival benefit favoring ICI-ICI strategy in PDL1(+) and ICI-VEGFR TKI in PDL1(-) patients. Study design has been developed to demonstrate that ICI-ICI is superior to ICI-VEGFR TKI in prolonging Overall Survival (OS) for PDL1(+) patients and to demonstrate that ICI-VEGFR TKI is superior to ICI-ICI in prolonging Progression Free Survival (PFS) and OS for PDL1(-) patients.
• Histologically confirmed metastatic (AJCC Stage IV) renal cell carcinoma with a clear-cell component.
• Intermediate- or poor-risk mRCC as defined by IMDC classification.
• Adult male or female patients (≥ 18 years of age at inclusion).
• Karnofsky Performance Status (KPS) ≥70%.
• Adequate organ and marrow function, according to investigator assessment and
∙ Absolute neutrophil count (ANC) ≥ 1000/μL (≥ 1.5 GI/L)
‣ Platelets ≥ 100,000/μL (≥ 100 GI/L)
‣ Hemoglobin ≥ 8 g/dL (≥ 80 g/L)
‣ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.
‣ Calculated creatinine clearance ≥ 30 mL/min (≥ 0.67 mL/sec) using the CKD- EPI equation
• Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed.
• Patient should be able and willing to comply with study visits and procedures as per protocol
• Patients must be affiliated to a social security system or beneficiary of the same
• Female patients must either be of non-reproductive potential or must have a negative serum pregnancy test within 14 days prior to the administration of study drug. Childbearing potential women must have agreed to use one barrier method of contraception, such as condom, plus an additional highly effective method of contraception during treatment on this trial and for up to 5 months after the last dose of study treatment.
⁃ Fertile men with a female partner of childbearing potential must agree to use one barrier method of contraception, such as condom, during treatment on this trial and for up to 4 months after the last dose of treatment. Their women of childbearing potential partner must agree to use a highly effective method of contraception during the same period.
⁃ Female subjects of childbearing potential must not be pregnant at screening.