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The approval was based on data from the CLEAR study (Study 307)/KEYNOTE-581 trial (ClinicalTrials.gov, NCT02811861). This was a phase Ⅲ, multicenter, open-label, randomized controlled trial that enrolled 1,069 patients with advanced renal cell carcinoma (RCC) who were receiving first-line treatment, regardless of the tumor programmed death-ligand 1 (PD-L1) expression status. Patients with active autoimmune diseases or those requiring immunosuppressive therapy were ineligible for enrollment. Randomization was stratified by geographic region (North America and Western Europe vs. the rest of the world) and Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk group (favorable vs. intermediate vs. poor risk).
Patients were randomly assigned in a 1:1:1 ratio to one of the three treatment groups as follows:
1. Lenvatinib (20 mg orally once daily) in combination with pembrolizumab (200 mg intravenously every 3 weeks, for up to 24 months of treatment);
2. Lenvatinib (18 mg orally once daily) in combination with everolimus (5 mg orally once daily);
3. Sunitinib (50 mg orally once daily, administered for 4 weeks followed by a 2-week treatment-free interval).
Treatment continued until the occurrence of unacceptable toxicity or disease progression. Patients could continue to receive pembrolizumab plus lenvatinib even if they had experienced disease progression as defined by the Response Evaluation Criteria in Solid Tumors (RECIST), provided that their clinical status remained stable and investigators assessed that they were still deriving clinical benefit from the treatment. The maximum treatment duration for pembrolizumab was 24 months, whereas lenvatinib could be administered for more than 24 months. Tumor assessments were performed at baseline and then every 8 weeks thereafter.
Based on the results of the phase Ⅲ CLEAR/KEYNOTE-581 trial: compared with sunitinib, pembrolizumab combined with lenvatinib significantly reduced the risk of disease progression or death by 61% in patients.
from FDA，2024.06
