Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial

Kei Muro, Hyuncheol Chung, Veena Shankaran, Ravit Geva, Daniel Catenacci, Shilpa Gupta, Joseph Paul Eder, Talia Golan, Dung T. Le, Barbara Burtness, Autumn J. McRee, Chia Chi Lin, Kumudu Pathiraja, Jared Lunceford, Kenneth Emancipator, Jonathan Juco, Minori Koshiji, Yung Jue Bang

Research output: Contribution to journalArticle

404 Citations (Scopus)

Abstract

Background Expression of PD-L1 has been shown to be upregulated in some patients with gastric cancer. As part of the phase 1b KEYNOTE-012 study, we aimed to assess the safety and activity of the anti-PD-1 antibody pembrolizumab in patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Methods This study was a multicentre, open-label, phase 1b trial done at 13 cancer research centres in the USA, Israel, Japan, South Korea, and Taiwan. We enrolled patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Patients received intravenous pembrolizumab at 10 mg/kg once every 2 weeks for 24 months or until progression or unacceptable toxic effects occurred. Response was assessed every 8 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. The primary objectives were safety in patients who received at least one dose of pembrolizumab and the proportion of patients achieving overall responses in patients who received at least one pembrolizumab dose and who either had a post-baseline scan or who discontinued therapy because of clinical disease progression or a treatment-related adverse event before the first post-baseline scan. The study is registered with ClinicalTrials.gov, number NCT01848834, and is ongoing but no longer enrolling patients. Findings From Oct 23, 2013, to May 5, 2014, 39 patients were enrolled. 36 were evaluable for response by central assessment. Eight (22%, 95% CI 10–39) patients were judged to have had an overall response at central review; all responses were partial. All 39 patients were included in the safety analyses. Five (13%) patients had a total of six grade 3 or 4 treatment-related adverse events, consisting of two cases of grade 3 fatigue, one case each of grade 3 pemphigoid, grade 3 hypothyroidism, and grade 3 peripheral sensory neuropathy, and one case of grade 4 pneumonitis. No treatment-related deaths occurred. Interpretation In this population of patients with recurrent or metastatic PD-L1-positive gastric cancer, pembrolizumab had a manageable toxicity profile and promising antitumour activity, warranting further study in phase 2 and 3 trials. Funding Merck & Co.

Original languageEnglish
Pages (from-to)717-726
Number of pages10
JournalThe Lancet Oncology
Volume17
Issue number6
DOIs
Publication statusPublished - 2016 Jun 1

Fingerprint

Stomach Neoplasms
pembrolizumab
Stomach
Adenocarcinoma
Safety
Bullous Pemphigoid
Republic of Korea
Poisons
Peripheral Nervous System Diseases
Israel
Therapeutics
Patient Safety
Hypothyroidism
Taiwan
Fatigue
Disease Progression
Pneumonia
Japan
Antibodies

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Muro, Kei ; Chung, Hyuncheol ; Shankaran, Veena ; Geva, Ravit ; Catenacci, Daniel ; Gupta, Shilpa ; Eder, Joseph Paul ; Golan, Talia ; Le, Dung T. ; Burtness, Barbara ; McRee, Autumn J. ; Lin, Chia Chi ; Pathiraja, Kumudu ; Lunceford, Jared ; Emancipator, Kenneth ; Juco, Jonathan ; Koshiji, Minori ; Bang, Yung Jue. / Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012) : a multicentre, open-label, phase 1b trial. In: The Lancet Oncology. 2016 ; Vol. 17, No. 6. pp. 717-726.
@article{f68cf737389746648f9fd4d6af13b12e,
title = "Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial",
abstract = "Background Expression of PD-L1 has been shown to be upregulated in some patients with gastric cancer. As part of the phase 1b KEYNOTE-012 study, we aimed to assess the safety and activity of the anti-PD-1 antibody pembrolizumab in patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Methods This study was a multicentre, open-label, phase 1b trial done at 13 cancer research centres in the USA, Israel, Japan, South Korea, and Taiwan. We enrolled patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Patients received intravenous pembrolizumab at 10 mg/kg once every 2 weeks for 24 months or until progression or unacceptable toxic effects occurred. Response was assessed every 8 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. The primary objectives were safety in patients who received at least one dose of pembrolizumab and the proportion of patients achieving overall responses in patients who received at least one pembrolizumab dose and who either had a post-baseline scan or who discontinued therapy because of clinical disease progression or a treatment-related adverse event before the first post-baseline scan. The study is registered with ClinicalTrials.gov, number NCT01848834, and is ongoing but no longer enrolling patients. Findings From Oct 23, 2013, to May 5, 2014, 39 patients were enrolled. 36 were evaluable for response by central assessment. Eight (22{\%}, 95{\%} CI 10–39) patients were judged to have had an overall response at central review; all responses were partial. All 39 patients were included in the safety analyses. Five (13{\%}) patients had a total of six grade 3 or 4 treatment-related adverse events, consisting of two cases of grade 3 fatigue, one case each of grade 3 pemphigoid, grade 3 hypothyroidism, and grade 3 peripheral sensory neuropathy, and one case of grade 4 pneumonitis. No treatment-related deaths occurred. Interpretation In this population of patients with recurrent or metastatic PD-L1-positive gastric cancer, pembrolizumab had a manageable toxicity profile and promising antitumour activity, warranting further study in phase 2 and 3 trials. Funding Merck & Co.",
author = "Kei Muro and Hyuncheol Chung and Veena Shankaran and Ravit Geva and Daniel Catenacci and Shilpa Gupta and Eder, {Joseph Paul} and Talia Golan and Le, {Dung T.} and Barbara Burtness and McRee, {Autumn J.} and Lin, {Chia Chi} and Kumudu Pathiraja and Jared Lunceford and Kenneth Emancipator and Jonathan Juco and Minori Koshiji and Bang, {Yung Jue}",
year = "2016",
month = "6",
day = "1",
doi = "10.1016/S1470-2045(16)00175-3",
language = "English",
volume = "17",
pages = "717--726",
journal = "The Lancet Oncology",
issn = "1470-2045",
publisher = "Lancet Publishing Group",
number = "6",

}

Muro, K, Chung, H, Shankaran, V, Geva, R, Catenacci, D, Gupta, S, Eder, JP, Golan, T, Le, DT, Burtness, B, McRee, AJ, Lin, CC, Pathiraja, K, Lunceford, J, Emancipator, K, Juco, J, Koshiji, M & Bang, YJ 2016, 'Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial', The Lancet Oncology, vol. 17, no. 6, pp. 717-726. https://doi.org/10.1016/S1470-2045(16)00175-3

Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012) : a multicentre, open-label, phase 1b trial. / Muro, Kei; Chung, Hyuncheol; Shankaran, Veena; Geva, Ravit; Catenacci, Daniel; Gupta, Shilpa; Eder, Joseph Paul; Golan, Talia; Le, Dung T.; Burtness, Barbara; McRee, Autumn J.; Lin, Chia Chi; Pathiraja, Kumudu; Lunceford, Jared; Emancipator, Kenneth; Juco, Jonathan; Koshiji, Minori; Bang, Yung Jue.

In: The Lancet Oncology, Vol. 17, No. 6, 01.06.2016, p. 717-726.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012)

T2 - a multicentre, open-label, phase 1b trial

AU - Muro, Kei

AU - Chung, Hyuncheol

AU - Shankaran, Veena

AU - Geva, Ravit

AU - Catenacci, Daniel

AU - Gupta, Shilpa

AU - Eder, Joseph Paul

AU - Golan, Talia

AU - Le, Dung T.

AU - Burtness, Barbara

AU - McRee, Autumn J.

AU - Lin, Chia Chi

AU - Pathiraja, Kumudu

AU - Lunceford, Jared

AU - Emancipator, Kenneth

AU - Juco, Jonathan

AU - Koshiji, Minori

AU - Bang, Yung Jue

PY - 2016/6/1

Y1 - 2016/6/1

N2 - Background Expression of PD-L1 has been shown to be upregulated in some patients with gastric cancer. As part of the phase 1b KEYNOTE-012 study, we aimed to assess the safety and activity of the anti-PD-1 antibody pembrolizumab in patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Methods This study was a multicentre, open-label, phase 1b trial done at 13 cancer research centres in the USA, Israel, Japan, South Korea, and Taiwan. We enrolled patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Patients received intravenous pembrolizumab at 10 mg/kg once every 2 weeks for 24 months or until progression or unacceptable toxic effects occurred. Response was assessed every 8 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. The primary objectives were safety in patients who received at least one dose of pembrolizumab and the proportion of patients achieving overall responses in patients who received at least one pembrolizumab dose and who either had a post-baseline scan or who discontinued therapy because of clinical disease progression or a treatment-related adverse event before the first post-baseline scan. The study is registered with ClinicalTrials.gov, number NCT01848834, and is ongoing but no longer enrolling patients. Findings From Oct 23, 2013, to May 5, 2014, 39 patients were enrolled. 36 were evaluable for response by central assessment. Eight (22%, 95% CI 10–39) patients were judged to have had an overall response at central review; all responses were partial. All 39 patients were included in the safety analyses. Five (13%) patients had a total of six grade 3 or 4 treatment-related adverse events, consisting of two cases of grade 3 fatigue, one case each of grade 3 pemphigoid, grade 3 hypothyroidism, and grade 3 peripheral sensory neuropathy, and one case of grade 4 pneumonitis. No treatment-related deaths occurred. Interpretation In this population of patients with recurrent or metastatic PD-L1-positive gastric cancer, pembrolizumab had a manageable toxicity profile and promising antitumour activity, warranting further study in phase 2 and 3 trials. Funding Merck & Co.

AB - Background Expression of PD-L1 has been shown to be upregulated in some patients with gastric cancer. As part of the phase 1b KEYNOTE-012 study, we aimed to assess the safety and activity of the anti-PD-1 antibody pembrolizumab in patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Methods This study was a multicentre, open-label, phase 1b trial done at 13 cancer research centres in the USA, Israel, Japan, South Korea, and Taiwan. We enrolled patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Patients received intravenous pembrolizumab at 10 mg/kg once every 2 weeks for 24 months or until progression or unacceptable toxic effects occurred. Response was assessed every 8 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. The primary objectives were safety in patients who received at least one dose of pembrolizumab and the proportion of patients achieving overall responses in patients who received at least one pembrolizumab dose and who either had a post-baseline scan or who discontinued therapy because of clinical disease progression or a treatment-related adverse event before the first post-baseline scan. The study is registered with ClinicalTrials.gov, number NCT01848834, and is ongoing but no longer enrolling patients. Findings From Oct 23, 2013, to May 5, 2014, 39 patients were enrolled. 36 were evaluable for response by central assessment. Eight (22%, 95% CI 10–39) patients were judged to have had an overall response at central review; all responses were partial. All 39 patients were included in the safety analyses. Five (13%) patients had a total of six grade 3 or 4 treatment-related adverse events, consisting of two cases of grade 3 fatigue, one case each of grade 3 pemphigoid, grade 3 hypothyroidism, and grade 3 peripheral sensory neuropathy, and one case of grade 4 pneumonitis. No treatment-related deaths occurred. Interpretation In this population of patients with recurrent or metastatic PD-L1-positive gastric cancer, pembrolizumab had a manageable toxicity profile and promising antitumour activity, warranting further study in phase 2 and 3 trials. Funding Merck & Co.

UR - http://www.scopus.com/inward/record.url?scp=84964779633&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964779633&partnerID=8YFLogxK

U2 - 10.1016/S1470-2045(16)00175-3

DO - 10.1016/S1470-2045(16)00175-3

M3 - Article

C2 - 27157491

AN - SCOPUS:84964779633

VL - 17

SP - 717

EP - 726

JO - The Lancet Oncology

JF - The Lancet Oncology

SN - 1470-2045

IS - 6

ER -