Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 Mar;34(3):251-261.
doi: 10.1016/j.annonc.2022.12.007. Epub 2022 Dec 16.

Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial

A T C Chan  1 , V H F Lee  2 , R-L Hong  3 , M-J Ahn  4 , W Q Chong  5 , S-B Kim  6 , G F Ho  7 , P B Caguioa  8 , N Ngamphaiboon  9 , C Ho  10 , M A S A Aziz  11 , Q S Ng  12 , C-J Yen  13 , N Soparattanapaisarn  14 , R K-C Ngan  15 , S K Kho  16 , M L A Tiambeng  17 , T Yun  18 , V Sriuranpong  19 , A P Algazi  20 , A Cheng  21 , E Massarelli  22 , R F Swaby  23 , S Saraf  23 , J Yuan  23 , L L Siu  24
Affiliations
Free article
Clinical Trial

Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial

A T C Chan et al. Ann Oncol. 2023 Mar.
Free article

Abstract

Background: Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, programmed death ligand 1 (PD-L1)-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented.

Patients and methods: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1 : 1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary endpoint was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population.

Results: Between 5 May 2016 and 28 May 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cut-off (30 November 2020) was 45.1 months (interquartile range, 39.0-48.8 months). Median OS was 17.2 months [95% confidence interval (CI) 11.7-22.9 months] with pembrolizumab and 15.3 months (95% CI 10.9-18.1 months) with chemotherapy [hazard ratio, 0.90 (95% CI 0.67-1.19; P = 0.2262)]. Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage).

Conclusion: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events.

Keywords: immunotherapy; nasopharyngeal cancer; pembrolizumab; programmed death-1 (PD-1).

PubMed Disclaimer

Conflict of interest statement

Disclosure ATCC had received honoraria from Beigene, Springer, Merck, and Pfizer; advisory/consulting fees from Merck Serono, Cullinan Management Inc., Tessa Therapeutics, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD); research grants/funding to their institution from Merck Serono, MSD, Novartis, Pfizer, and Eli Lilly; support for travel/accommodations/expenses from Bristol Myers Squibb (BMS), MSD, Pfizer, Roche, Novartis, and AstraZeneca; full/part-time employment at The Chinese University of Hong Kong; and reports non-remunerated activities with Immunomic Therapeutics, Inc., Angene Biotechnology, and Owlstone Medical Limited. VHFL has received honoraria from Amgen, AstraZeneca, Boston Scientific, Eli Lilly, MSD, Novartis, Pfizer, and Takeda; advisory/consultancy and speaker bureau fees from AQUILAB, AstraZeneca, and Merck; and research grant/funding from AstraZeneca and Roche. RLH received support to their institution from MSD for conduct of the clinical trial during the preparation of the submitted work and grants or contracts to the institution from MSD outside the submitted work. MJA has received honoraria from AstraZeneca, Takeda, MSD, ONO, BMS, Lilly, Amgen, Merck, and Roche; advisory/consultancy fees from AstraZeneca, Takeda, MSD, ONO, BMS, Lilly, Amgen, Merck, Roche, and Alpha Pharmaceuticals; and research grant/funding to their institution from AstraZeneca and Roche. WQC has received support for travel/accommodations/expenses from Amgen and MSD. SBK received support to their institution from MSD for conduct of the clinical trial during the preparation of the submitted work; and grants or contracts to their institution from Novartis, Sanofi-Aventis, and DongKook Pharm Co; consulting fees from Novartis, AstraZeneca, Lilly, DaeHwa Pharmaceutical Co, Ltd, ISU Abix, and Daiichi-Sankyo; and stock or stock options from Genopeaks and Neogene TC outside the submitted work. GFH has received grants to their institution from MSD during the conduct of the study; and has received grants or contracts to their institution from MSD, AstraZeneca, Eli Lilly, Arcus Biosciences, Inc., Pfizer, INEX EpiTherapeutics Pte. Ltd., Roche, Astellas, Novartis, Tessa Therapeutics, Regeneron, and Samsung Bioepis; honoraria/speaker bureau fees from Eli Lilly, Merck, and Pfizer; support for attending meetings and/or travel from AstraZeneca and BMS Pte Ltd; and has participated in data safety monitoring board or advisory board for Pfizer, Boehringer Ingelheim, AstraZeneca, MIMS, MSD, and Eli Lilly outside the submitted work. PBC received support to their institution from MSD for conduct of the clinical trial during the preparation of the submitted work and honoraria from Roche, Novartis, AstraZeneca, and MSD outside the submitted work. NN has received grants to their institution from MSD during the conduct of the study; has received grants to their institution from MSD, Roche, Exelixis, RAPT Therapeutics, BeiGene, and Pfizer; has received honoraria from Roche, AstraZeneca, Amgen, MSD, and Taiho; and has participated in advisory boards for MSD, Amgen, Novartis, Bayer, AstraZeneca, Claris, and Eli Lilly outside the submitted work. CH received honoraria from AstraZeneca, BMS, Boehringer Ingelheim, Bayer, Eisai, EMD Serono, Merck, Novartis, and Roche; research grants from AstraZeneca, MSD, and Roche; and other support for travel from Roche. QSN received support to their institution from MSD for conduct of the clinical trial during the preparation of the submitted work; received support for attending meetings and/or travel from MSD; and participated in an advisory board for MSD outside the submitted work. CJY received support to their institution from MSD for conduct of the clinical trial during the preparation of the submitted work. NS received support to their institution from MSD for conduct of the clinical trial during the preparation of the submitted work and honoraria from MSD, AstraZeneca, Roche, and BMS outside the submitted work. RKCN has received advisory/consulting fees from Pfizer, Novartis, Sanofi, AstraZeneca, Lilly, MSD, Zai Lab, Roche, and Eisai; speaker bureau fees from Novartis, AstraZeneca, Sanofi, Pfizer, Zai Lab, Eisai, Lilly, and MSD; research grant/funding to their institution from Pfizer; and support for travel/accommodations/expenses from Pfizer, Astellas, Novartis, MSD, Roche, Eisai, Merck, Sanofi, BMS, and Zai Lab. MLAT has received honoraria, speaker bureau, and advisory/consultancy fees from MSD. VS has received honoraria from AstraZeneca, Novartis, Eisai, Taiho, MSD, BMS, Pfizer, and Amgen; advisory/consultancy fees from AstraZeneca, Novartis, MSD, BMS, and Amgen; and research grant/funding from AstraZeneca, Novartis, MSD, Regeneron, and Roche. APA has received honoraria from OncoSec Medical, Inc.; advisory/consultancy fees from OncoSec and Valitor; research grant/funding to their institution from Merck, BMS, Acerta, Sensei, AstraZeneca, Incyte, Regeneron, Tessa, Lilly, Checkmate, and Idera; support for travel/accommodations/expenses from Sensei and OncoSec; is a shareholder/stock/holder/has stock options in OncoSec and Valitor; and reports non-remunerated activities with Sensei, Regeneron, and Sanofi. EM received honoraria from AstraZeneca and Merck; advisory/consultancy fees from Merck, BMS, Sanofi, Genentech, Lilly, and Janssen; speaker bureau fees from AstraZeneca, Takeda, Merck, and Lilly; research grant/funding to their institution from Pfizer, GSK, Merck, Tessa, AstraZeneca, BMS, and Genentech; and support for travel/accommodations/expenses from BMS, Pfizer, Merck, AstraZeneca, and Genentech. RFS was an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, during the time of the conduct of the study and is currently an employee of Prelude Therapeutics. SS is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and owns stock in Merck & Co., Inc., Rahway, NJ, USA. JY is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. LLS received support to their institution from MSD for conduct of the clinical trial and consulting/advisory board fees during the preparation of the submitted work; grants or contracts to their institution from Novartis, BMS, Pfizer, Boehringer Ingelheim, GSK, Roche/Genentech, Karyopharm, AstraZeneca, Astellas, Bayer, AbbVie, Amgen, Symphogen, Intensity Therapeutics, Mirati, Shattuck, and Avid; consulting fees from Pfizer, Celgene, AstraZeneca, MorphoSys, Roche, Oncorus, Symphogen, Seattle Genetics, GSK, Voronoi, Treadwell Therapeutics, Arvinas, Tessa, Navire, Relay, Rubius, Janpix, and Daiichi Sankyo; and their spouse is cofounder of Treadwell Therapeutics and owns stock in Agios outside the submitted work. All other authors have declared no conflicts of interest. Data sharing Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD), is committed to providing qualified scientific researchers access to anonymized data and clinical study reports from the company’s clinical trials for the purpose of conducting legitimate scientific research. MSD is also obligated to protect the rights and privacy of trial participants and, as such, has a procedure in place for evaluating and fulfilling requests for sharing company clinical trial data with qualified external scientific researchers. The MSD data sharing website (available at: http://engagezone.msd.com/ds_documentation.php) outlines the process and requirements for submitting a data request. Applications will be promptly assessed for completeness and policy compliance. Feasible requests will be reviewed by a committee of MSD subject matter experts to assess the scientific validity of the request and the qualifications of the requestors. In line with data privacy legislation, submitters of approved requests must enter into a standard data-sharing agreement with MSD before data access is granted. Data will be made available for request after product approval in the United States and EU or after product development is discontinued. There are circumstances that may prevent MSD from sharing requested data, including country or region-specific regulations. If the request is declined, it will be communicated to the investigator. Access to genetic or exploratory biomarker data requires a detailed, hypothesis-driven statistical analysis plan that is collaboratively developed by the requestor and MSD subject matter experts; after approval of the statistical analysis plan and execution of a data-sharing agreement, MSD will either perform the proposed analyses and share the results with the requestor or will construct biomarker covariates and add them to a file with clinical data that is uploaded to an analysis portal so that the requestor can perform the proposed analyses.

Publication types

MeSH terms