Analyses on impact of tumor burden at progression and changes in IMDC from baseline in patients (pts) with advanced renal cell carcinoma (aRCC) treated with lenvatinib + pembrolizumab (L+P) in the phase 3 CLEAR trial.

531 Background: L+P significantly improved efficacy vs sunitinib in treatment-naïve pts with aRCC in the CLEAR trial (Motzer 2021). We report data from further analyses on the impact of tumor burden at the time of progression and shifts in IMDC scores in the L+P arm of the CLEAR study. Methods: Study design has been reported (Motzer 2021). Data cutoff for analyses was July 31, 2022 (median follow-up: ~4 years; Motzer 2024). Data herein are limited to the L+P arm of CLEAR. Medians for survival from either progression or randomization (i.e., overall survival) were estimated by Kaplan-Meier method, and 95% CIs were estimated via generalized Brookmeyer and Crowley method. Survival was assessed according to percent changes from baseline in target lesion diameters of pts at progression (on L+P) by tertiles (T1: ≤-61%; T2: >-61%-≤-34%; T3: >-34%-≤51%). Changes in IMDC score from baseline were reported at 6 months to assess treatment impact on prognosis. Results: Pts with a larger percentage decrease in sums of target lesion diameters at progression had longer median survival (months [95% CI]) from time of progression vs pts with smaller percentage decreases in tumor size (T1 [n=59], 35.6 [28.4-39.2]; T2 [n=58], 24.4 [15.5-34.5]; T3 [n=59], 20.2 [16.4-26.9]). Similar trends were observed with overall survival (from randomization; T1, not estimable [49.9-NE]; T2, 43.0 [33.0-NE]; T3, 31.5 [22.4-34.4]). Most pts, irrespective of tumor shrinkage at progression, received subsequent systemic anticancer medication during survival follow-up (T1: 63%; T2: 59%; T3: 71%). Pts received an anti-VEGF therapy (46%; 45%; 59%) as their first subsequent medication more frequently than any other medications. The most frequently used anti-VEGF therapies were cabozantinib (22%; 29%; 29%), sunitinib (12%; 3%; 20%), and axitinib (7%; 3%; 8%). At 6 months, IMDC score stayed the same or decreased from baseline in most pts; ≤10% of pts had increases in IMDC score, regardless of score at baseline (Table). Conclusions: Pts in the L+P arm with lower disease burden at progression showed improved prognosis, highlighting the importance of deep tumor response when considering treatment sequence. IMDC risk scores were typically constant or improved in pts treated with L+P; data are limited by missing pts. Clinical trial information: NCT02811861 . L+P arm IMDC score at 6 months, n (%) Baseline IMDC score a Decreased by ≥1 points Remained constant Increased by 1 point Increased by ≥2 points Missing b 0 (n=110) NA 84 (76) 9 (8) 2 (2) 15 (14) 1 (n=137) 25 (18) 82 (60) 8 (6) 2 (1) 20 (15) 2 (n=72) 34 (47) 18 (25) 5 (7) 1 (1) 14 (19) 3 (n=26) 18 (69) 0 0 0 8 (31) 4 (n=5) 4 (80) 0 0 0 1 (20) 5 (n=1) 1 (100) 0 0 0 0 Total (n=355) 84 (24) 186 (52) 22 (6) 5 (1) 58 (16) a 4 pts had a missing score at baseline. b IMDC prognostic score was derived based on total risk score from 6 prognostic factors at baseline and month 6 (+/- 2 weeks).