Efficacy and Safety of Pembrolizumab (MK-3475) With Platinum Doublet Chemotherapy as Neoadjuvant/Adjuvant Therapy for Participants With Resectable Stage II, IIIA, and Resectable IIIB (T3-4N2) Non-small Cell Lung Cancer (MK-3475-671/KEYNOTE-671)

Summary

This trial will evaluate the safety and efficacy of pembrolizumab (MK-3475) in combination with platinum doublet neoadjuvant chemotherapy (NAC) before surgery \[neoadjuvant phase\], followed by pembrolizumab alone after surgery \[adjuvant phase\] in participants with resectable stage II, IIIA, and resectable IIIB (T3-4N2) non-small cell lung cancer (NSCLC). The primary hypotheses of this study are that neoadjuvant pembrolizumab (vs. placebo) in combination with NAC, followed by surgery and adjuvant pembrolizumab (vs. placebo) will improve: 1) event free survival (EFS) by biopsy assessed by local pathologist or by investigator-assessed imaging using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1); and 2) overall survival (OS).

Timeline

Start

2018-04-24

Primary completion

2023-07-10

Completion

2026-06-29

Outcome

Met primary endpoint

registry analysis (superiority test); NAC + Neoadjuvant/Adjuvant Pembrolizumab vs NAC + Neoadjuvant/Adjuvant Placebo; p <0.00001; Hazard Ratio (HR) 0.59 (95% CI 0.48 to 0.72); Log Rank NCT03425643 ↗

registry analysis (superiority test); NAC + Neoadjuvant/Adjuvant Pembrolizumab vs NAC + Neoadjuvant/Adjuvant Placebo; p = 0.00517; Hazard Ratio (HR) 0.72 (95% CI 0.56 to 0.93); Log Rank NCT03425643 ↗

Publications

• Results Spicer JD, Garassino MC, Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Chen KN, Dooms C, Majem M, Eigendorff E, Martinengo GL, Bylicki O, Rodriguez-Abreu D, Chaft JE, Novello S, Yang J, Arunachalam A, Keller SM, Samkari A, Gao S; KEYNOTE-671 Investigators. Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with neoadjuvant chemotherapy alone in patients with early-stage non-small-cell lung cancer (KEYNOTE-671): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024 Sep 28;404(10459):1240-1252. doi: 10.1016/S0140-6736(24)01756-2. Epub 2024 Sep 14.
• Results Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, Chen KN, Dooms C, Majem M, Eigendorff E, Martinengo GL, Bylicki O, Rodriguez-Abreu D, Chaft JE, Novello S, Yang J, Keller SM, Samkari A, Spicer JD; KEYNOTE-671 Investigators. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Aug 10;389(6):491-503. doi: 10.1056/NEJMoa2302983. Epub 2023 Jun 3.
• Tsuboi M, Wakelee H, Garassino MC, Gao S, Luft A, Chen KN, Spicer JD, Zhu Y, Saji H, Okada M, Vanakesa T, Chen H, Zhao G, Ikeda N, Jones DR, Weksler B, Huang CS, Jensen E, Keller SM, Samkari A, Liberman M. A Subgroup Analysis of Perioperative Pembrolizumab in Clinical Stage II Non-Small-Cell Lung Cancer from the Randomized KEYNOTE-671 Study. Eur J Cardiothorac Surg. 2026 Mar 10;68(3):ezag028. doi: 10.1093/ejcts/ezag028.
• Aredo JV, Wakelee HA. Top advances of the year: Perioperative therapy for lung cancer. Cancer. 2024 Sep 1;130(17):2897-2903. doi: 10.1002/cncr.35357. Epub 2024 May 8.
• Romero Roman A, Campo-Canaveral de la Cruz JL, Macia I, Escobar Campuzano I, Figueroa Almanzar S, Delgado Roel M, Galvez Munoz C, Garcia Fontan EM, Muguruza Trueba I, Romero Vielva L, Cano Garcia JR, Martinez Tellez E, Partida Gonzalez C, Jimenez Lopez MF, Jimenez Maestre U, Mongil Poce R, Sanchez Lorente D, Alvarez Kindelan A, Provencio Pulla M. Outcomes of surgical resection after neoadjuvant chemoimmunotherapy in locally advanced stage IIIA non-small-cell lung cancer. Eur J Cardiothorac Surg. 2021 Jul 14;60(1):81-88. doi: 10.1093/ejcts/ezab007.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Pembrolizumab	Monoclonal antibody	200 mg	Intravenous
Background	Cisplatin	Other / unclassified	75 mg/m2	Intravenous
Background	Gemcitabine	Small molecule	1000 mg/m2	Intravenous
Background	Pemetrexed	Small molecule	500 mg/m2	Intravenous

Indications