The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer

Yelena Y. Janjigian; Akihito Kawazoe; Patricio Yañez; Ning Li; Sara Lonardi; Oleksii Kolesnik; Olga Barajas; Yuxian Bai; Lin Shen; Yong Tang; Lucjan S. Wyrwicz; Jianming Xu; Kohei Shitara; Shukui Qin; Eric Van Cutsem; Josep Tabernero; Lie Li; Sukrut Shah; Pooja Bhagia; Hyun Cheol Chung

doi:10.1038/s41586-021-04161-3

The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer

Yelena Y. Janjigian, Akihito Kawazoe, Patricio Yañez, Ning Li, Sara Lonardi, Oleksii Kolesnik, Olga Barajas, Yuxian Bai, Lin Shen, Yong Tang, Lucjan S. Wyrwicz, Jianming Xu, Kohei Shitara, Shukui Qin, Eric Van Cutsem, Josep Tabernero, Lie Li, Sukrut Shah, Pooja Bhagia, Hyun Cheol Chung

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

123 Citations (Scopus)

Abstract

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) amplification or overexpression occurs in approximately 20% of advanced gastric or gastro-oesophageal junction adenocarcinomas^1–3. More than a decade ago, combination therapy with the anti-HER2 antibody trastuzumab and chemotherapy became the standard first-line treatment for patients with these types of tumours⁴. Although adding the anti-programmed death 1 (PD-1) antibody pembrolizumab to chemotherapy does not significantly improve efficacy in advanced HER2-negative gastric cancer⁵, there are preclinical^6–19 and clinical^20,21 rationales for adding pembrolizumab in HER2-positive disease. Here we describe results of the protocol-specified first interim analysis of the randomized, double-blind, placebo-controlled phase III KEYNOTE-811 study of pembrolizumab plus trastuzumab and chemotherapy for unresectable or metastatic, HER2-positive gastric or gastro-oesophageal junction adenocarcinoma²² (https://clinicaltrials.gov, NCT03615326). We show that adding pembrolizumab to trastuzumab and chemotherapy markedly reduces tumour size, induces complete responses in some participants, and significantly improves objective response rate.

Original language	English
Pages (from-to)	727-730
Number of pages	4
Journal	Nature
Volume	600
Issue number	7890
DOIs	https://doi.org/10.1038/s41586-021-04161-3
Publication status	Published - 2021 Dec 23

Bibliographical note

Funding Information:
Acknowledgements This study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Y.Y.J. was additionally supported by Memorial Sloan Kettering Cancer Center National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748. We thank the patients and their families and caregivers for participating in the study; the investigators and site personnel; and the following employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA: C. S. Shih for study oversight and M. A. Leiby for medical writing and editorial assistance.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.

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Janjigian, Y. Y., Kawazoe, A., Yañez, P., Li, N., Lonardi, S., Kolesnik, O., Barajas, O., Bai, Y., Shen, L., Tang, Y., Wyrwicz, L. S., Xu, J., Shitara, K., Qin, S., Van Cutsem, E., Tabernero, J., Li, L., Shah, S., Bhagia, P., & Chung, H. C. (2021). The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature, 600(7890), 727-730. https://doi.org/10.1038/s41586-021-04161-3

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abstract = "Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) amplification or overexpression occurs in approximately 20% of advanced gastric or gastro-oesophageal junction adenocarcinomas1–3. More than a decade ago, combination therapy with the anti-HER2 antibody trastuzumab and chemotherapy became the standard first-line treatment for patients with these types of tumours4. Although adding the anti-programmed death 1 (PD-1) antibody pembrolizumab to chemotherapy does not significantly improve efficacy in advanced HER2-negative gastric cancer5, there are preclinical6–19 and clinical20,21 rationales for adding pembrolizumab in HER2-positive disease. Here we describe results of the protocol-specified first interim analysis of the randomized, double-blind, placebo-controlled phase III KEYNOTE-811 study of pembrolizumab plus trastuzumab and chemotherapy for unresectable or metastatic, HER2-positive gastric or gastro-oesophageal junction adenocarcinoma22 (https://clinicaltrials.gov, NCT03615326). We show that adding pembrolizumab to trastuzumab and chemotherapy markedly reduces tumour size, induces complete responses in some participants, and significantly improves objective response rate.",

author = "Janjigian, {Yelena Y.} and Akihito Kawazoe and Patricio Ya{\~n}ez and Ning Li and Sara Lonardi and Oleksii Kolesnik and Olga Barajas and Yuxian Bai and Lin Shen and Yong Tang and Wyrwicz, {Lucjan S.} and Jianming Xu and Kohei Shitara and Shukui Qin and {Van Cutsem}, Eric and Josep Tabernero and Lie Li and Sukrut Shah and Pooja Bhagia and Chung, {Hyun Cheol}",

note = "Funding Information: Acknowledgements This study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Y.Y.J. was additionally supported by Memorial Sloan Kettering Cancer Center National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748. We thank the patients and their families and caregivers for participating in the study; the investigators and site personnel; and the following employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA: C. S. Shih for study oversight and M. A. Leiby for medical writing and editorial assistance. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

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Janjigian, YY, Kawazoe, A, Yañez, P, Li, N, Lonardi, S, Kolesnik, O, Barajas, O, Bai, Y, Shen, L, Tang, Y, Wyrwicz, LS, Xu, J, Shitara, K, Qin, S, Van Cutsem, E, Tabernero, J, Li, L, Shah, S, Bhagia, P & Chung, HC 2021, 'The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer', Nature, vol. 600, no. 7890, pp. 727-730. https://doi.org/10.1038/s41586-021-04161-3

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AU - Janjigian, Yelena Y.

AU - Kawazoe, Akihito

AU - Yañez, Patricio

AU - Li, Ning

AU - Lonardi, Sara

AU - Kolesnik, Oleksii

AU - Barajas, Olga

AU - Bai, Yuxian

AU - Shen, Lin

AU - Tang, Yong

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AU - Xu, Jianming

AU - Shitara, Kohei

AU - Qin, Shukui

AU - Van Cutsem, Eric

AU - Tabernero, Josep

AU - Li, Lie

AU - Shah, Sukrut

AU - Bhagia, Pooja

AU - Chung, Hyun Cheol

N1 - Funding Information: Acknowledgements This study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Y.Y.J. was additionally supported by Memorial Sloan Kettering Cancer Center National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748. We thank the patients and their families and caregivers for participating in the study; the investigators and site personnel; and the following employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA: C. S. Shih for study oversight and M. A. Leiby for medical writing and editorial assistance. Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature Limited.

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N2 - Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) amplification or overexpression occurs in approximately 20% of advanced gastric or gastro-oesophageal junction adenocarcinomas1–3. More than a decade ago, combination therapy with the anti-HER2 antibody trastuzumab and chemotherapy became the standard first-line treatment for patients with these types of tumours4. Although adding the anti-programmed death 1 (PD-1) antibody pembrolizumab to chemotherapy does not significantly improve efficacy in advanced HER2-negative gastric cancer5, there are preclinical6–19 and clinical20,21 rationales for adding pembrolizumab in HER2-positive disease. Here we describe results of the protocol-specified first interim analysis of the randomized, double-blind, placebo-controlled phase III KEYNOTE-811 study of pembrolizumab plus trastuzumab and chemotherapy for unresectable or metastatic, HER2-positive gastric or gastro-oesophageal junction adenocarcinoma22 (https://clinicaltrials.gov, NCT03615326). We show that adding pembrolizumab to trastuzumab and chemotherapy markedly reduces tumour size, induces complete responses in some participants, and significantly improves objective response rate.

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The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer

Abstract

Bibliographical note

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