A randomized phase 2 trial of lenvatinib plus pembrolizumab with or without stereotactic body radiotherapy in patients with metastatic renal cell carcinoma, low tumor burden, and stable disease (LASER).

Abstract

TPS583 Background: Lenvatinib plus pembrolizumab (Len+P) is an established first-line regimen for metastatic clear cell renal cell carcinoma (mRCC). In the CLEAR study, patients with low tumor burden derived substantial benefit; however, ~20% achieved only stable disease (SD) as best response. In the VOLGA study, outcomes were improved when even a single lesion was irradiated during targeted therapy. We hypothesize that adding stereotactic body radiotherapy (SBRT) to multiple lesions in patients with SD during Len+P therapy will increase the objective response rate (ORR) and potentially improve overall survival (OS). Methods: LASER is a randomized, multicenter, phase 2 study. Eligible patients must have histologically confirmed mRCC, sum of target lesion diameters ≥7 cm, ECOG PS 0–2, and no prior systemic therapy for metastatic disease. All patients receive 12 weeks of induction therapy with Len (20 mg daily) plus P (200 mg Q3W). Imaging is performed per RECIST v1.1 to classify response as complete/partial response, SD, or progression. Patients with SD are randomized 1:1 to: (1) Len+P+SBRT or (2) Len+P alone. In the SBRT arm, up to 3 lesions are selected for irradiation by a multidisciplinary team. The primary endpoint is ORR of non-irradiated lesions after randomization, assessed every 12 weeks per RECIST v1.1. Secondary endpoints include progression-free survival (PFS), OS, response from irradiated lesions, and safety. The study is powered to detect an increase in ORR from 15% (control) to 50% (SBRT arm), with α = 0.05 and 80% power, requiring 27 patients per arm (54 randomized). Total planned enrollment is 150 patients to account for the proportion achieving SD following induction. Clinical trial information: KCRB-092025/2.