PLLBA-01 PEMBROLIZUMAB (PEMBRO) VS PLACEBO AS POST NEPHRECTOMY ADJUVANT THERAPY FOR PATIENTS (pts) WITH RENAL CELL CARCINOMA (RCC): RANDOMIZED, DOUBLE-BLIND, PHASE 3 KEYNOTE-564 STUDY

Abstract

INTRODUCTION AND OBJECTIVE: Effective therapy to reduce risk of RCC relapse after surgery remains an unmet need. Adjuvant immune therapy is a potential strategy for these pts. The KEYNOTE-564 trial (NCT03142334) evaluated pembro vs placebo as adjuvant therapy for pts with RCC. METHODS: KEYNOTE-564 is a phase 3 trial of pembro vs placebo for ≥17 cycles (z1 yr) in pts with histologically confirmed clear cell RCC, with pT2, Gr 4 or sarcomatoid, N0 M0; pT3 or pT4, any Gr, N0 M0; any pT, any Gr, N+M0; or M1 NED (no evidence of disease after primary tumor + soft tissue metastases completely resected ≥1 yr from nephrectomy). Pts had undergone surgery ≥12 wks prior to randomization; had no prior systemic therapy; had ECOG PS 0 or 1. The primary endpoint was disease-free survival (DFS) per investigator assessment in all randomized pts (ITT population). Overall survival (OS) was a key secondary endpoint. Safety in all treated pts was a secondary endpoint. RESULTS: 994 pts were randomized 1:1 to pembro (n=496) or placebo (n=498). Median (range) time from randomization to data cutoff date of Dec 14, 2020 was 24.1 (14.9±41.5) mo. No pts remained on study treatment. Baseline characteristics were generally balanced between arms. At first prespecified interim analysis, the primary endpoint of DFS was met (median not reached [NR] for both arms, HR 0.68, 95% CI 0.53±0.87; p=0.0010 [one-sided]). Estimated DFS rate at 24 mo was 77.3% with pembro vs 68.1% with placebo. Overall, DFS benefit was consistent across subgroups. 51 OS events were observed (18 in the pembro arm, 33 in the placebo arm). Median OS was NR for both arms (HR 0.54, 95% CI 0.30±0.96; p=0.0164 [onesided]); the p-value did not cross the statistical hypothesis testing boundary. Estimated OS rate at 24 mo was 96.6% with pembro vs 93.5% with placebo. 470 pts (96.3%) and 452 pts (91.1%) experienced ≥1 all-cause adverse events (AEs) with pembro vs placebo, respectively. Grade 3-5 all-cause AEs occurred in 158 pts (32.4%) with pembro and 88 pts (17.7%) with placebo. No deaths related to pembro occurred. CONCLUSIONS: Pembro demonstrated a statistically significant and clinically meaningful improvement in DFS vs placebo in pts with RCC at high risk of recurrence following surgery. Additional followup is planned for the key secondary endpoint of OS. KEYNOTE-564 is the first positive phase 3 study with adjuvant immunotherapy in RCC and these results support pembro as a potential new standard of care for pts with RCC in the adjuvant setting.