# KEYNOTE-001 (Garon 2015): pembrolizumab in non-small-cell lung cancer and the 50% PD-L1 cut-off

Source: https://onco.cc/key-papers/paper-keynote-001-pembrolizumab-nsclc-nejm-2015/  
OnCo record `paper-keynote-001-pembrolizumab-nsclc-nejm-2015` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The large early trial that showed pembrolizumab shrinks about a fifth of advanced lung cancers, with responses that last, and that identified a PD-L1 score of 50% or more as the group most likely to benefit.

## Summary

KEYNOTE-001 treated 495 patients with advanced non-small-cell lung cancer, both previously treated and untreated, with pembrolizumab at several doses and schedules. The overall response rate was about 19% with a median duration of response around a year and no clear difference between doses. A training and validation approach on PD-L1 immunohistochemistry defined a tumour proportion score of at least 50% as the threshold at which response and survival were markedly better, a cut-off adopted by KEYNOTE-024 and now used in clinics worldwide.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2015
- DOI: 10.1056/NEJMoa1501824
- Authors: Garon EB, Rizvi NA, Hui R, et al.
- Findings: 495 patients with advanced NSCLC treated with pembrolizumab at 2 or 10 mg/kg every three weeks or 10 mg/kg every two weeks.; Objective response rate 19.4% overall; median duration of response 12.5 months.; PD-L1 tumour proportion score of at least 50%, seen in 23.2% of patients, was associated with a response rate of 45.2% and longer progression-free and overall survival.; Treatment-related grade 3 or higher adverse events in 9.5% of patients.
- What it means: This trial gave lung cancer its immunotherapy biomarker. The 50% PD-L1 cut-off decides today whether a patient with advanced lung cancer can start immunotherapy alone or needs chemotherapy added, and the five-year follow-up later showed long-term survivors among first-line responders.
- Caveats: Single-arm study with several dose cohorts; the cut-off was derived and validated within the same trial.; PD-L1 testing depends on the assay and the sample and misses some responders.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa1501824
- ClinicalTrials.gov NCT01295827: https://clinicaltrials.gov/study/NCT01295827

## Connected records

- key papers: [Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC](https://onco.cc/key-papers/paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020/), [KEYNOTE-010 (Herbst 2016): pembrolizumab versus docetaxel in previously treated PD-L1-positive lung cancer](https://onco.cc/key-papers/paper-keynote-010-lancet-2016/), [KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer](https://onco.cc/key-papers/paper-keynote-024-nejm-2016/)
- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [PD-L1-high non-small-cell lung cancer without a driver mutation](https://onco.cc/cancers/pdl1-high-nsclc/)
- targets: [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- terms: [Objective response rate (ORR)](https://onco.cc/terms/orr/), [PD-L1 expression testing (22C3, SP142, SP263)](https://onco.cc/terms/pd-l1-testing/), [Tumour proportion score (TPS)](https://onco.cc/terms/tps/)
- roadmaps: [Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/)

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