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
. 2025 Aug;116(8):2208-2217.
doi: 10.1111/cas.70082. Epub 2025 May 23.

KEYNOTE-A17: First-Line Pembrolizumab Plus Cisplatin-Pemetrexed in Japanese Participants With Advanced Pleural Mesothelioma

Takashi Kijima  1 , Terufumi Kato  2 , Yasushi Goto  3 , Kozo Kuribayashi  1 , Koji Mikami  1 , Yoshiki Negi  1 , Shuji Murakami  2 , Tatsuya Yoshida  3 , Masae Homma  4 , Akira Wakana  4 , Kazuo Noguchi  4 , Nobukazu Fujimoto  5
Affiliations
Clinical Trial

KEYNOTE-A17: First-Line Pembrolizumab Plus Cisplatin-Pemetrexed in Japanese Participants With Advanced Pleural Mesothelioma

Takashi Kijima et al. Cancer Sci. 2025 Aug.

Abstract

Pleural mesothelioma (PM) is an inflammatory cancer linked with asbestos exposure and has a poor prognosis. We report results of the phase 1b KEYNOTE-A17 study (NCT04153565) of first-line pembrolizumab plus chemotherapy in Japanese participants with advanced PM. Participants aged ≥ 20 years with previously untreated, histologically confirmed advanced or unresectable PM received pembrolizumab 200 mg every 3 weeks (Q3W) for ≤ 35 cycles with cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 Q3W for 4-6 cycles. Primary endpoints were the rate of dose-limiting toxicities (DLTs), adverse events (AEs), and treatment discontinuations due to AEs. DLTs were assessed during cycle 1 in 18 participants, and having ≤ 8 participants with DLTs was considered tolerable. AEs were graded per NCI CTCAE 5.0. Tumor response was evaluated per modified RECIST for PM by the investigator. Among 19 participants enrolled, the median study follow-up was 30.8 (range, 27.8-33.3) months (data cutoff September 21, 2022). Of 18 participants evaluated for DLTs, 2 (11%) experienced 4 DLTs (hypoalbuminemia, malaise, pyrexia in 1 participant; uveitis in 1 participant). 18/19 participants (95%) experienced treatment-related AEs; 14 (74%) had grade 3-4 events (no grade 5). Treatment-related AEs led to discontinuation of any drug in 5 participants (26%). The objective response rate was 74% (partial response, n = 14), and the median (range) duration of response was 16.8 (3.0-26.3+) months. First-line pembrolizumab plus chemotherapy was tolerable based on the low incidence of DLTs and showed acceptable safety and preliminary antitumor activity in Japanese participants with advanced PM. Trial Registration: NCT04153565.

Keywords: Japan; cisplatin; pembrolizumab; pemetrexed; pleural mesothelioma.

PubMed Disclaimer

Conflict of interest statement

Takashi Kijima: Support for the current manuscript: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Honoraria for lecture fee: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Advisory board: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Terufumi Kato: Support for the current manuscript: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Honoraria for speaker to self: Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi‐Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck KGaA, MSD, Novartis, Ono, Pfizer, Taiho, and Takeda. Grants for commissioned/joint research to institution: AbbVie, Amgen, Arrivent, AstraZeneca, Bayer, BeiGene, BluePrint, Bristol Myers Squibb, Chugai, Daiichi‐Sankyo, Eli Lilly, Gilead, GlaxoSmithKline, Haihe, Janssen, Merck KGaA, MSD, Novartis, Pfizer, Regeneron, and Takeda. Honoraria for IDMC or advisory board meeting to self: AstraZeneca, BeiGene, Chugai, Daiichi‐Sankyo, Janssen, Merck KGaA, MSD, Novartis, Pfizer. Employer (spouse): Eli Lilly. Yasushi Goto: Honoraria to self: Eli Lilly, Chugai, Taiho, Boehringer Ingelheim, Ono, Bristol Myers Squibb, Pfizer, MSD, Novartis, Merck, Thermo Fischer. Grants for commissioned/joint research: AbbVie, Eli Lilly, Pfizer, Bristol Myers Squibb, Ono, Novartis, Kyorin, Daiichi‐Sankyo, Novartis, Prefered Network. Participation on data safety monitoring board or advisory board to self: AstraZeneca, Chugai, Boehringer Ingelheim, Eli Lilly, Taiho, Pfizer, Novartis, Guardant Health Inc., Illumina, Daiichi‐Sankyo, Ono Pharmaceutical, Bristol Myers Squibb, MSD. Leadership or fiduciary role: Cancer Net Japan, JAMT. Editorial Board Member: Cancer Science. Shuji Murakami: Grants or contracts to institution: AstraZeneca, Takeda, Chugai Pharma, Sanofi, MSD, Daiichi‐Sankyo, Ono Pharmaceutical, Janssen Pharma. Honoraria to self: AstraZeneca, Chugai Pharma, Takeda, Eli Lilly, MSD, Pfizer, Novartis, Taiho Pharmaceutical. Tatsuya Yoshida: Grants or contracts from: Novartis, AbbVie, Amgen, Daiichi‐Sankyo, AstraZeneca, MSD, Chugai, Astellas, Medpace, Boehringer Ingelheim, BMS, Ono, and Merck Biopharma. Payment or honoraria: Novartis, Daiichi‐Sankyo, AstraZeneca, MSD, Chugai, BMS, Ono, Takeda, Pfizer, Lilly, and Merck Biopharma. Participation on a Data Safety Monitoring Board or Advisory Board: Novartis, MSD, Amgen, Chugai, Pfizer, and Boehringer Ingelheim. Masae Homma: Employee of MSD K.K., Tokyo, Japan. Akira Wakana: Employee of MSD K.K., Tokyo, Japan, and owns stock in Merck & Co., Inc., Rahway, NJ, USA. Kazuo Noguchi: Employee of MSD K.K., Tokyo, Japan. Nobukazu Fujimoto: Payment or honoraria to self: Ono Pharmaceutical, Bristol Myers Squibb, AstraZeneca, Chugai Pharmaceutical, MSD, Nihon Kayaku, Boehringer Ingelheim. Participation on a Data Safety Monitoring Board or Advisory Board to self: Ono Pharmaceutical, AstraZeneca. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
CONSORT flow diagram for the KEYNOTE‐A17 study. aOne participant withdrew consent during cycle 1 without a DLT and, per protocol, was excluded from the DLT‐evaluable population.
FIGURE 2
FIGURE 2
Changes from baseline in size of target lesions per modified RECIST for PM by investigator review. (A) Best change from baseline in tumor size. (B) Percentage change from baseline in tumor size over time. CPS, combined positive score; PD‐L1, programmed cell death ligand 1; PM, pleural mesothelioma; RECIST, Response Evaluation Criteria in Solid Tumors. [Correction added on 9 June 2025, after first online publication. “weeks” has been amended to “months” in the horizontal axis of Figure 2.]
FIGURE 3
FIGURE 3
Time to response and time to progression per modified RECIST for PM by investigator review. Bar lengths indicate time to last response assessment. aAll other participants represented in the figure had epithelioid tumors. CPS, combined positive score; PD‐L1, programmed cell death ligand 1; PM, pleural mesothelioma; RECIST, Response Evaluation Criteria in Solid Tumors.
FIGURE 4
FIGURE 4
Kaplan–Meier survival estimates. (A) Progression‐free survival per modified RECIST for PM by investigator review. (B) Overall survival. NR, not reached; PM, pleural mesothelioma; RECIST, Response Evaluation Criteria in Solid Tumors.
See this image and copyright information in PMC

References

    1. Gray S. G. and Mutti L., “Immunotherapy for Mesothelioma: A Critical Review of Current Clinical Trials and Future Perspectives,” Translational Lung Cancer Research 9 (2020): S100–S119. - PMC - PubMed
    1. Tolani B., Acevedo L. A., Hoang N. T., and He B., “Heterogeneous Contributing Factors in MPM Disease Development and Progression: Biological Advances and Clinical Implications,” International Journal of Molecular Sciences 19 (2018): 238 [Epub]. - PMC - PubMed
    1. Mott F. E., “Mesothelioma: A Review,” Ochsner Journal 12 (2012): 70–79. - PMC - PubMed
    1. Shavelle R., Vavra‐Musser K., Lee J., and Brooks J., “Life Expectancy in Pleural and Peritoneal Mesothelioma,” Lung Cancer (International Edition) 2017 (2017): 2782590. - PMC - PubMed
    1. Robinson B. M., “Malignant Pleural Mesothelioma: An Epidemiological Perspective,” Annals of Cardiothoracic Surgery 1 (2012): 491–496. - PMC - PubMed

Publication types

MeSH terms

Supplementary concepts

Associated data