6MO Pembrolizumab plus ipilimumab or placebo in previously untreated metastatic NSCLC with PD-L1 tumor proportion score ≥50%: KEYNOTE-598 3-year follow-up

Abstract

At protocol-specified interim analysis 1 (IA1; data cutoff Sep 1, 2020) of the phase 3 KEYNOTE-598 study (NCT03302234), adding ipilimumab (ipi) to pembrolizumab (pembro) did not improve OS (HR, 1.08) or PFS (HR, 1.06) vs placebo (pbo) + pembro in patients (pts) with previously untreated stage IV NSCLC with PD-L1 tumor proportion score (TPS) ≥50%. Per external DMC recommendation at IA1, ipi and pbo were discontinued and pembro monotherapy continued in both arms. We report 13 additional mo follow-up from IA1 and outcomes of pts who completed 35 cycles of pembro and pts who started second-course pembro. Eligible pts were randomized 1:1 to ipi 1 mg/kg or pbo Q6W for up to 18 doses (stratified by ECOG PS [0 vs 1], region [East Asia vs non-East Asia], and histology [squamous vs nonsquamous]). All pts received pembro 200 mg Q3W for up to 35 cycles. Dual primary endpoints were OS and PFS per RECIST v1.1 by BICR. 568 pts were randomized to pembro + ipi vs pembro + pbo (n = 284 each). Median time from randomization to data cutoff (Oct 1, 2021) was 33.6 (range, 25.4-44.6) mo. After discontinuing ipi/pbo for all pts, median OS and PFS remained similar between groups (Table). Grade 3-5 treatment-related AEs occurred in 99/282 (35.1%) vs 57/281 (20.3%) pts in the pembro + ipi vs pembro + pbo arms, respectively. Among 52 pts vs 71 pts initially treated with pembro + ipi vs pembro + pbo who completed 35 cycles of pembro, ORR was 88.5% vs 87.3%, respectively; OS and PFS rates 1 y from completing pembro were 86.3% vs 87.6% and 72.8% vs 83.5%, respectively. 11 pts started second-course pembro.Table: 6MOPembro + Ipi (n = 284)Pembro + Pbo (n = 284)Median OS, mo (95% CI)22.1 (17.1-27.4)22.7 (19.0-26.8)OS HR (95% CI)1.05 (0.85-1.29)2-y OS rate, % (95% CI)48.0 (42.1-53.7)48.5 (42.5-54.2)Median PFS, mo (95% CI)8.2 (6.1-10.6)8.4 (6.3-10.5)PFS HR (95% CI)0.99 (0.81–1.21)2-y PFS rate, % (95% CI)27.2 (21.9-32.9)25.1 (19.9-30.6)ORR, % (95% CI)46.5 (40.6-52.5)46.1 (40.2-52.1)Median DOR, mo (range)22.1 (1.1+ to 36.8+)18.9 (2.0+ to 42.6+)"+" indicates no PD by the time of last disease assessment. Open table in a new tab "+" indicates no PD by the time of last disease assessment. With continued follow-up, results do not show a survival benefit with ipi + pembro; 2-y OS rates were similar between groups and safety favored pembro alone. More pts in the pembro + pbo arm completed 35 cycles, and most who completed pembro were alive without PD 1 y after completion. Pembro monotherapy remains a standard of care therapy for metastatic NSCLC with PD-L1 TPS ≥50%.