Perioperative Lenvatinib With Pembrolizumab in Patients With Locally Advanced Nonmetastatic Clear Cell Renal Cell Carcinoma

PRIMARY OBJECTIVE:

I. To assess the objective response rate (complete and partial responses), following the administration of lenvatinib and pembrolizumab for a total of 4 cycles (12 weeks) in patients with locally-advanced, biopsy-proven non-metastatic clear cell renal cell carcinoma (ccRCC) prior to undergoing nephrectomy (partial or radical).

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of neoadjuvant lenvatinib plus pembrolizumab in a presurgical population as well as the safety of adjuvant pembrolizumab post-surgery.

II. To determine the clinical outcomes including disease-free survival (DFS) and overall survival (OS) of patients with non-metastatic ccRCC treated with neoadjuvant lenvatinib and pembrolizumab and adjuvant pembrolizumab.

III. To evaluate surgery-related complications and outcomes as per the Clavien-Dindo classification system.

EXPLORATORY OBJECTIVES:

I. To evaluate changes in biomarkers of immune activation and gene expression before, during and after treatment.

II. To assess the quality of life, frailty and sarcopenia of patients before and after treatment.

OUTLINE:

Patients receive lenvatinib orally (PO) once daily (QD) on days 1-21 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatments repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 14 days, then every 12 weeks thereafter.