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

Our plain-English summary of KEYNOTE-A17: First-Line Pembrolizumab Plus Cisplatin-Pemetrexed in Japanese Participants With Advanced Pleural Mesothelioma, by T. Kijima, T. Kato, Y. Goto, et al (Cancer Science, 2025).

The study

• Authors: T. Kijima, T. Kato, Y. Goto, K. Kuribayashi, K. Mikami, Y. Negi, S. Murakami, T. Yoshida, M. Homma, A. Wakana, K. Noguchi, N. Fujimoto
• Journal: Cancer Science
• Published: 2025;116(8):2208-2217
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2025 MSD K.K, a subsidiary of Merck & co., Inc and The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

In plain English

This phase 1b, open-label, single-arm trial, KEYNOTE-A17, tested the immunotherapy drug pembrolizumab with the chemotherapy drugs cisplatin and pemetrexed as first-line treatment for advanced disease. It enrolled 19 Japanese adults with advanced or unresectable pleural mesothelioma between December 2019 and May 2020. Fourteen of the 19 (74%) had prior asbestos exposure; fiber types were not described. Of 18 participants checked for dose-limiting toxicities, 2 (11%) had them, below the study's preset tolerability threshold. Treatment-related side effects occurred in 18 of 19 participants; 14 (74%) had grade 3 to 4 events and none a grade 5 treatment-related event. Side effects led 5 participants (26%) to stop at least one drug, and 5 (26%) had pneumonitis. The objective response rate was 74% (95% confidence interval 49% to 91%): 14 participants had a partial response. Median overall survival was 20.9 months (95% confidence interval 8.3 months to not reached), and 13 of 19 had died by data cutoff. The authors concluded the combination could offer a promising option. They noted the study was small and not powered to assess antitumor activity.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Multicenter, open-label, single-arm phase 1b clinical trial (KEYNOTE-A17)
• Who was studied: 19 Japanese participants aged at least 20 years with previously untreated, histologically confirmed advanced or unresectable pleural mesothelioma. They were enrolled at Japanese centres between December 12, 2019 and May 28, 2020, after 22 were screened. Median age was 70 (range 54–78) and 15 were male. Tumor types were 15 epithelioid, 2 sarcomatoid and 2 biphasic. Per Table 1, 6 (32%) had earlier systemic (neo)adjuvant therapy, completed at least 6 months before enrollment, and 4 (21%) had earlier major surgery.
• Exposure: Treatment studied was pembrolizumab 200 mg every 3 weeks (up to 35 cycles) with cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 every 3 weeks for 4–6 cycles. Asbestos exposure was recorded only as a baseline characteristic: 14 of 19 (74%) had prior exposure, listed in Table 1 as environmental exposure. No fiber types are reported.
• Main results:
  • Of 18 participants evaluable for dose-limiting toxicities, 2 (11%) had a total of four DLTs: hypoalbuminemia, malaise and pyrexia in one participant, and uveitis in the other.
  • 18 of 19 participants (95%) had at least one treatment-related adverse event.
  • Grade 3–4 treatment-related adverse events occurred in 14 of 19 participants (74%), and there were no grade 5 treatment-related adverse events.
  • Treatment-related adverse events led 5 of 19 participants (26%) to discontinue at least one study drug.
  • Pneumonitis occurred in 5 of 19 participants (26%). The 2 with grade 3 pneumonitis both discontinued treatment.
  • One participant died from bacterial pneumonia, which the investigator did not consider related to study treatment.
  • Among all 19 participants, the objective response rate was 74% (95% CI, 49%–91%).
  • The best overall response was a partial response in 14 participants and stable disease in 4, giving a disease control rate of 95%.
  • Median duration of response was 16.8 months (range 3.0 to 26.3+ months).
  • Objective response rate was 73% in the 15 participants with epithelioid tumors and 75% in the 4 with non-epithelioid tumors. It was 80% in the 5 with PD-L1 CPS of at least 1 and 100% in the 3 with CPS less than 1. The authors noted the subgroups were small.
  • Median progression-free survival was 13.8 months (95% CI, 4.8–27.4 months), and the estimated 12-month progression-free survival rate was 64%.
  • By data cutoff, 13 of 19 participants (68%) had died.
  • Median overall survival was 20.9 months (95% CI, 8.3 months to not reached), and the estimated 12-month overall survival rate was 68%.
• The authors' conclusion: The authors concluded that pembrolizumab plus cisplatin and pemetrexed had an acceptable safety profile in these Japanese participants. They also concluded that their results provide preliminary evidence the combination could offer a promising treatment option for Japanese patients with advanced pleural mesothelioma.
• Limitations the authors state:
  • The small study population makes results among subgroups difficult to interpret.
  • The study was not powered to assess antitumor activity.
  • Tumor samples for PD-L1 testing were not required, so PD-L1 status (CPS) was unknown for many participants.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pembrolizumab (Keytruda), Cisplatin, Pemetrexed (Alimta), Pleural Mesothelioma, Asbestos Exposure, Prognosis, Chemotherapy, Unresectable.

Related studies

• First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma — E. Fujimoto, T. Kijima, et al. (2017)
• JME-001 phase II trial of first-line combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable malignant pleural mesothelioma — Y. Miyamoto, T. Kozuki, et al. (2021)
• Bevacizumab plus cisplatin/pemetrexed then bevacizumab alone for unresectable malignant pleural mesothelioma: A Japanese safety study — T. Nakano, K. Kuribayashi, et al. (2021)
• Efficacy and safety of pembrolizumab in patients with advanced mesothelioma in the open-label, single-arm, phase 2 KEYNOTE-158 study — T.A. Yap, K. Nakagawa, et al. (2021)
• First-line chemotherapy with liposomal doxorubicin plus cisplatin for patients with advanced malignant pleural mesothelioma: phase II trial — Ó. Arrieta, L.A. Medina, et al. (2012)
• Comparison of cisplatin plus pemetrexed and cisplatin plus gemcitabine for the treatment of malignant pleural mesothelioma in Japanese patients — T. Shukuya, T. Takahashi, et al. (2014)

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