Abstract 6MO
Background
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.
Methods
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.
Results
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: 6MO
| Pembro + 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.
Conclusions
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%.
Clinical trial identification
NCT03302234.
Editorial acknowledgement
Writing support was provided by Christabel Wilson, MSc, of ICON plc (North Wales, PA, USA), funded by MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
D. Rodriguez Abreu: Financial Interests, Personal, Other, Honoraria for lectures and consulting: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer, Roche; Financial Interests, Personal, Funding: MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. M. Reck: Financial Interests, Personal, Advisory Board: Eli Lilly, MSD Oncology, Merck Serono, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, Roche/Genentech, AbbVie, Amgen, Mirati Therapeutics, Samsung Bioepis. Speakers bureau: Roche/Genentech, Eli Lilly, MSD Oncology, Merck Serono; Financial Interests, Personal, Funding: MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. M.A.N. Şendur: Financial Interests, Personal, Other, Honoraria for lectures and speaking: Bristol Myers Squibb, Pfizer, Amgen, Novartis, Roche, Astellas, MSD, Bayer, Novartis, Janssen; Financial Interests, Personal, Funding: MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. K. Park: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Ono Pharmaceutical, Bristol Myers Squibb, MSD, Blueprint Medicines, Amgen, Merck KGaA, LOXO, AbbVie, Daiichi Sankyo, Boehringer Ingelheim, Johnson & Johnson, Eisai, Puma Biotechnology; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Funding: AstraZeneca, MSD Oncology, MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. D.H. Lee: Financial Interests, Personal, Other, Honoraria: AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol Myers Squibb, Chong Kun Dang Pharmaceutical, CJ Healthcare, Lilly, Janssen, Merck, MSD, Mundipharma, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Samyang, ST Cube, Takeda, AbbVie; Financial Interests, Personal, Funding: MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Other, Travel, accommodations, expenses: Takeda, Blueprint Medicines. I. Cicin: Financial Interests, Personal, Advisory Board: Pfizer, MSD, Roche, Novartis/Ipsen, Lilly, Bristol Myers Squibb, SERVIER, Abdi Ibrahim, Nobelpharma, AbbVie, Teva, Janssen Oncology; Financial Interests, Personal, Funding: MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Speaker’s Bureau: Novartis, Roche, Bristol Myers Squibb, Pfizer, Abdi Ibrahim. P.F. Yumuk: Financial Interests, Institutional, Advisory Board: Takeda, Roche, Bristol Myers Squibb; Financial Interests, Institutional, Speaker’s Bureau: Novo Nordisk (1st degree relative), Nestle Health Science (1st degree relative), Bristol Myers Squibb, Roche, AstraZeneca; Financial Interests, Institutional, Funding: Roche, Merck, MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Novartis. F.J. Orlandi: Financial Interests, Personal, Other, Honoraria: Roche/Genentech; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche/Genentech, Bristol Myers Squibb, MSD, Lilly, Pfizer, Novartis, Sanofi; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca/MedImmune, Roche; Financial Interests, Personal, Funding: AstraZeneca/MedImmune, Amgen, Genentech/Roche, Boehringer Ingelheim, Astellas Medivation, MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Bristol Myers Squibb, Celltrion, Pfizer, mAbxience, Nektar, Sanofi; Financial Interests, Personal, Other, Travel, accommodations, expenses: Pfizer, MSD, AstraZeneca/MedImmune, Roche, Bristol Myers Squibb, Genentech/Roche. T.A. Leal: Financial Interests, Personal, Other, Personal fees: AstraZeneca, Bayer, Blueprint, Bristol Myers Squibb, Boehringer Ingelheim, EMD Serono, Jazz Pharmaceuticals, Merck; Financial Interests, Personal, Funding: MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. N. Soparattanapaisarn: Financial Interests, Personal, Funding: MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. A. Langleben: Financial Interests, Personal, Funding: MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. R. Califano: Financial Interests, Personal, Stocks/Shares: The Christie Private Care; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Boehringer Ingelheim, Lilly Oncology, Roche, Pfizer, MSD, Bristol Myers Squibb, Takeda, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Lilly Oncology, Roche, Pfizer, MSD, Bristol Myers Squibb, Takeda, Novartis; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche, Pfizer, MSD, Bristol Myers Squibb, Takeda, Novartis; Financial Interests, Personal, Funding: Roche, AstraZeneca, Pfizer, Clovis, Lilly Oncology, MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Bristol Myers Squibb, AbbVie, Takeda, Novartis; Financial Interests, Personal, Other, Travel, accommodations, expenses: Roche, Lilly Oncology, MSD, Takeda. B. Medgyasszay: Financial Interests, Personal, Funding: MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. T. Hsia: Financial Interests, Personal, Funding: MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. G.A. Otterson: Financial Interests, Personal, Other, Consultant: Bristol Myers Squibb, Guardant Health, AstraZeneca, Gilead Biosciences, Novocure; Financial Interests, Personal, Funding: Pfizer, Bristol Myers Squibb, Merck, AstraZeneca, Array, Revolution Medicine, Genentech, MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. T. Woods, E. Jensen, A. Samkari: Financial Interests, Personal, Full or part-time Employment: MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Kenilworth, NJ, USA. M. Boyer: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, and MSD; Financial Interests, Institutional, Funding: Amgen, Ascentage, AstraZeneca, Bristol Myers Squibb, Genentech/Roche, Lilly, Merck KGaA, MSD, Novartis, Pfizer, MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.