Subgroup Analyses of Efficacy Outcomes by Baseline Tumor Size in the Phase 3, Open-Label CLEAR Trial.

364 Background: In the primary analysis of the phase 3 open-label CLEAR trial, lenvatinib + pembrolizumab (L+P) showed statistically significant and clinically meaningful improvements in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared with sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC) (Motzer NEJM 2021). Outcomes were further corroborated by results of the final prespecified analysis of CLEAR (Motzer ASCO 2023). We report efficacy outcomes per baseline tumor size in the L+P arm of CLEAR. Methods: 1069 treatment-naïve pts with aRCC and a clear-cell component were randomized (1:1:1) to: L 20 mg PO QD + P 200 mg IV Q3W; or L 18 mg + everolimus 5 mg PO QD; or S 50 mg PO QD (4 wks on/2 wks off). Stratification factors included geographic region and MSKCC prognostic risk group. IMDC risk groups (derived programmatically) are presented in this analysis. Efficacy outcomes were evaluated by quartiles of baseline sums of diameters of target lesions. Tumor assessments were performed by independent imaging review per RECIST v1.1. Results: Pts were grouped into 4 categories: ≤Q1 (34.72 mm), >Q1 - ≤Q2 (60.06 mm), >Q2 - ≤Q3 (108.56 mm) and >Q3 per baseline tumor sizes (Table). For pts with ≤Q1 baseline tumor sizes, 40.7% and 58.0% were in the favorable and intermediate + poor IMDC risk subgroups, respectively. For pts with >Q3 baseline tumor sizes, 6.3% and 93.8% were in the favorable and intermediate + poor IMDC risk groups, respectively. Median OS, PFS, ORR, complete response (CR), partial response (PR), and near-CR (PR with maximum tumor shrinkage ≥75%) by baseline tumor size categories are in the Table. Conclusions: In CLEAR, clinically meaningful efficacy with L+P was observed across pts with aRCC irrespective of their baseline tumor sizes. These results support the use of L+P for the 1L treatment of aRCC across pts with both low and high baseline tumor size. Clinical trial information: NCT02811861 . [Table: see text]