TY - JOUR
T1 - JME-001 phase II trial of first-line combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable malignant pleural mesothelioma
AU - Miyamoto, Yosuke
AU - Kozuki, Toshiyuki
AU - Aoe, Keisuke
AU - Wada, Sae
AU - Harada, Daijiro
AU - Yoshida, Michihiro
AU - Sakurai, Jun
AU - Hotta, Katsuyuki
AU - Fujimoto, Nobukazu
N1 - Funding Information:
Competing interests TK reports personal fees from Eli Lilly Japan, personal fees from Bristol Myers Squibb, personal fees from Ono Pharmaceutical, during the conduct of the study; grants and personal fees from Taiho Pharmaceutical, grants and personal fees from Kyowa Hakko Kirin, personal fees from AstraZeneca, personal fees from MSD, personal fees from Chugai Pharmaceutical, personal fees from Nippon Boehringer Ingelheim, personal fees from Merck Biopharma, personal fees from Nippon Kayaku, personal fees from Daiichi Sankyo, personal fees from Pfizer Japan, personal fees from Takeda Pharmaceutical, personal fees from Novartis, outside the submitted work. DH reports personal fees from Eli Lilly Japan, grants and personal fees from Bristol Myers Squibb, grants and personal fees from Ono Pharmaceutical, during the conduct of the study; personal fees from Kyowa Hakko Kirin, grants and personal fees from AstraZeneca, personal fees from Nippon Boehringer Ingelheim, grants and personal fees from MSD, personal fees from Taiho Pharmaceutical, grants and personal fees from Chugai Pharmaceutical, grants from Novartis, grants from Kissei Pharmaceutical, grants from Takeda Pharmaceutical, grants from Pfizer Japan, outside the submitted work. KA reports grants and personal fees from Eli Lilly Japan, grants and personal fees from Bristol Myers Squibb, grants and personal fees from Ono Pharmaceutical, during the conduct of the study; grants and personal fees from AstraZeneca, personal fees from Nippon Boehringer Ingelheim, grants and personal fees from MSD, grants from Novartis, outside the submitted work. KH reports grants from Bristol Meyers Squibb, MSD, AstraZeneca, Chugai and Eli Lilly Japan, and honoraria from Eli Lilly Japan, Bristol Meyers Squib, Ono, Pfizer, AstraZeneca, Chugai, Takeda, MSD, Nippon Kayaku, Taiho, and Boehringer Ingelheim. NF reports personal fees from Eli Lilly Japan, grants, personal fees and other from Bristol Myers Squibb, grants, personal fees and other from Ono Pharmaceutical, during the conduct of the study; grants from MSD, personal fees from Chugai, personal fees from Daiichi Sankyo, outside the submitted work. Other authors have stated that they have no conflicts of interest.
Funding Information:
Contributors YM, TK, KA, DH, and SW were involved in the acquisition of the data. MY was involved in analysis of the data. YM, TK, KA, JS, KH, and NF were involved in the interpretation of the data, writing or reviewing and editing the manuscript. NF approved the final version of the manuscript for submission. NF is responsible for the overall content as guarantor. Funding This work was supported by Ono Pharmaceutical and the Ministry of Health, Labor, and Welfare, Japan (grant number 180101-02).
Publisher Copyright:
© 2021, BMJ Publishing Group Ltd. All rights reserved.
PY - 2021/10/28
Y1 - 2021/10/28
N2 - JME-001 is a phase II trial assessing the efficacy and safety of cisplatin, pemetrexed, and nivolumab as first-line therapy in malignant pleural mesothelioma (MPM). Patients with untreated, unresectable MPM with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1 were included. The primary endpoint is the centrally reviewed objective response rate. The secondary endpoints include (1) response rate assessed by investigators, (2) disease control rate, (3) overall survival, (4) progression-free survival, (5) duration of response, and (6) time to response. Safety and adverse events will also be evaluated. Cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and nivolumab (360 mg/body) were administered intravenously every 3 weeks with a total of 4–6 cycles. If patients did not progress during the combination phase, maintenance therapy with nivolumab was administered until disease progression or unacceptable toxicity. Tissue samples were required and collected for programmed death ligand 1 analysis. Eighteen patients (mean age 69.2 years, 15 men) were enrolled between January 2018 and May 2019. The ECOG PS was 0 in 3 patients and 1 in 15 patients. Fourteen (77.8%; 95% CI 52.4% to 93.6%) patients had an objective response. The disease control rate was 94.4% (95% CI 72.7% to 99.9%). Fourteen (77.8%) patients had partial response (PR), three had stable disease, and one was not evaluable. Tumor shrinkage was observed in 10/14 (71.4%) patients with epithelioid, and 2/2 (100%) patients with sarcomatoid or biphasic histological subtype had PR. Ten (55.6%) patients experienced grade 3 or worse adverse events, including disorder of metabolism or nutrition (33.3%), loss of appetite (27.8%), anemia (16.7%), and hyponatremia (11.1%). No treatment-related deaths occurred. The safety and efficacy of this study strongly support a definitive trial of this combination. Trial registration number UMIN000030892.
AB - JME-001 is a phase II trial assessing the efficacy and safety of cisplatin, pemetrexed, and nivolumab as first-line therapy in malignant pleural mesothelioma (MPM). Patients with untreated, unresectable MPM with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1 were included. The primary endpoint is the centrally reviewed objective response rate. The secondary endpoints include (1) response rate assessed by investigators, (2) disease control rate, (3) overall survival, (4) progression-free survival, (5) duration of response, and (6) time to response. Safety and adverse events will also be evaluated. Cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and nivolumab (360 mg/body) were administered intravenously every 3 weeks with a total of 4–6 cycles. If patients did not progress during the combination phase, maintenance therapy with nivolumab was administered until disease progression or unacceptable toxicity. Tissue samples were required and collected for programmed death ligand 1 analysis. Eighteen patients (mean age 69.2 years, 15 men) were enrolled between January 2018 and May 2019. The ECOG PS was 0 in 3 patients and 1 in 15 patients. Fourteen (77.8%; 95% CI 52.4% to 93.6%) patients had an objective response. The disease control rate was 94.4% (95% CI 72.7% to 99.9%). Fourteen (77.8%) patients had partial response (PR), three had stable disease, and one was not evaluable. Tumor shrinkage was observed in 10/14 (71.4%) patients with epithelioid, and 2/2 (100%) patients with sarcomatoid or biphasic histological subtype had PR. Ten (55.6%) patients experienced grade 3 or worse adverse events, including disorder of metabolism or nutrition (33.3%), loss of appetite (27.8%), anemia (16.7%), and hyponatremia (11.1%). No treatment-related deaths occurred. The safety and efficacy of this study strongly support a definitive trial of this combination. Trial registration number UMIN000030892.
KW - clinical trials
KW - phase II as topic
UR - http://www.scopus.com/inward/record.url?scp=85118683857&partnerID=8YFLogxK
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U2 - 10.1136/jitc-2021-003288
DO - 10.1136/jitc-2021-003288
M3 - Article
C2 - 34711664
AN - SCOPUS:85118683857
VL - 9
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
SN - 2051-1426
IS - 10
M1 - e003288
ER -
