1895MO - Three-year follow-up results of the MERIT trial: A Japanese phase II study of nivolumab in malignant pleural mesothelioma

Background

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive malignancy with poor prognosis.In Japan, nivolumab was approved in August 2018 for patients with pemetrexed-platinum doublet-treated MPM based on the MERIT trial results.Here, we report the 3-year follow-up data of the MERIT trial to update the previous report.

Methods

Enrollment criteria were as follows: Japanese patients with advanced or metastatic MPM previously treated with up to two chemotherapy regimens, with histologically confirmed measurable lesions and an ECOG performance status (PS) of 0-1. There was no restriction on the programmed death-ligand 1 (PD-L1) status. Patients received nivolumab 240 mg/body every 2 weeks until disease progression or unacceptable toxicity was indicated. The primary endpoint was objective response rate (ORR) (mRECIST assessment by an independent review committee), and the secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Results

Thirty-four patients were enrolled in this study: 85.3% men; median age: 68.0 (43–78) years; PS 1: 61.8%; epithelioid/sarcomatoid/biphasic: 79.4%/8.8%/11.8%; 1 prior regimen: 70.6%; and (PD-L1≥1%)/(PD-L1 < 1%)/not evaluable: 58.8%/35.3%/5.9%.At a minimum follow-up of 36 months, ORR and DCR were 29.4% [n=10, 95% CI: 16.8–46.2] and 67.6% (n=23,95% CI: 50.8–80.9), respectively. Median DOR was 11.1 months (95% CI: 3.5–28.6+). At the data cutoff date (November 2019), seven patients were alive. Two- and three-year OS rates were 35.3% (95% CI: 19.9–51.0) and 23.5% (95% CI: 11.1–38.6), respectively. Furthermore, two- and three-year PFS rates were 17.0% (95% CI: 6.3–32.0) and 12.7% (95% CI: 3.7–27.6), respectively.Overall, 26 patients (76.5%) experienced treatment-related adverse events (TRAEs) and 11 (32.4%) were grade 3-4. The most commonly reported TRAEs were skin disorders (n=6,17.6%), elevated lipase (n=5,14.7%), elevated amylase levels (n=4,11.8%), and diarrhea (n=4,11.8%).

Conclusions

Nivolumab showed durable long-term efficacy and a manageable safety profile in Japanese patients with MPM receiving second- and third-line treatment.

Clinical trial identification

JapicCTI-163247.

Editorial acknowledgement

Legal entity responsible for the study

Ono Pharmaceutical Co. Ltd.

Funding

Ono Pharmaceutical Co. Ltd., Bristol-Myers Squibb Company.

Disclosure

H. Hayashi: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Boehringer Ingelheim Japan Inc.; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly Japan K.K.; Speaker Bureau/Expert testimony, Research grant/Funding (self): Ono Pharmaceutical Co. Ltd.; Speaker Bureau/Expert testimony: Taiho Pharmaceutical Co. Ltd.; Speaker Bureau/Expert testimony: Kyowa Hakko Kirin Co. Ltd.; Speaker Bureau/Expert testimony: Pfizer Japan Inc.; Advisory/Consultancy: Chugai Pharmaceutical Co. Ltd.; Advisory/Consultancy: MerckBiopharma. T. Kijima: Honoraria (self): Ono Pharmaceutical Co. Ltd. K. Aoe: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ono Pharmaceutical Co. Ltd.; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb Company; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Sharp & Dohme Corp.; Research grant/Funding (institution): Novartis Pharma K.K.; Research grant/Funding (institution): AstraZeneca K.K.; Research grant/Funding (institution): Pfizer Inc. T. Kato: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca K.K.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme Corp.; Honoraria (self), Research grant/Funding (institution): Pfizer Inc.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly K.K.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Biopharma Co., Ltd; Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Nippon Boehringer Ingelheim Co., Ltd.; Honoraria (self): Takeda Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): AbbVie GK; Honoraria (self), Research grant/Funding (institution): Novartis Pharma K.K.; Honoraria (self), Research grant/Funding (institution): Taiho Phamaceutical Co., Ltd.; Honoraria (self): Daiichi Sankyo Co., Ltd.; Honoraria (self): Shionogi & Co., Ltd.; Honoraria (self): Nippon Kayaku Co., Ltd.; Research grant/Funding (institution): Regeneron Pharmaceuticals, Inc; Research grant/Funding (institution): Amgen inc.; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb K.K.. N. Fujimoto: Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Bristol-Myers Squibb K.K.; Honoraria (self): Daiichi Sankyo Co., Ltd. K. Nakagawa: Honoraria (self), Advisory/Consultancy: KYORIN Pharmaceutical Co., Ltd.; Honoraria (self), Advisory/Consultancy: Pfizer Japan Inc.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical Co.,Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly Japan K.K.; Honoraria (self): Roche Diagnostics K.K; Honoraria (self): Nippon Kayaku Co.,Ltd; Honoraria (self), Research grant/Funding (institution): Bayer Yakuhin, Ltd; Honoraria (self), Research grant/Funding (institution): AstraZeneca K.K.; Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): MSD K.K.; Honoraria (self), Research grant/Funding (institution): Nippon Boehringer Ingelheim Co.,Ltd.; Honoraria (self): Merck Biopharma Co., Ltd.; Honoraria (self): AbbVie Inc.; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical Co.,Ltd.; Honoraria (self), Research grant/Funding (institution): Novartis Pharma K.K.; Honoraria (self): Medical Review Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb Company; Honoraria (self): Medical Mobile Communications co., Ltd; Honoraria (self): 3H Clinical Trial Inc.; Honoraria (self): YODOSHA CO., LTD.; Research grant/Funding (institution): Takeda Pharmaceutical Co.,Ltd.; Research grant/Funding (institution): Daiichi Sankyo Co., Ltd.; Research grant/Funding (institution): Eisai Co., Ltd.; Research grant/Funding (institution): EPS Corporation.; Research grant/Funding (institution): Syneos Health.; Research grant/Funding (institution): Pfizer R&D Japan G.K.; Research grant/Funding (institution): IQVIA Services JAPAN K.K.; Research grant/Funding (institution): AbbVie Inc.; Research grant/Funding (institution): A2 Healthcare Corp.; Research grant/Funding (institution): SymBio Pharmaceuticals Limited.; Research grant/Funding (institution): EPS International Co.,Ltd.; Research grant/Funding (institution): Pfizer Japan Inc.; Research grant/Funding (institution): Otsuka Pharmaceutical Co., Ltd. Y. Takeda: Research grant/Funding (institution): Taiho Phamaceutical Co., Ltd.; Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd. T. Hida: Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): AstraZeneca K.K.; Honoraria (self): Bristol-Myers Squibb K.K.; Honoraria (self): MSD. J. Hirano: Full/Part-time employment: Ono Pharmaceutical Co., Ltd. Y. Namba: Full/Part-time employment: Ono Pharmaceutical Co., Ltd.. Y. Ohe: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): ONO; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb K.K.; Advisory/Consultancy, Research grant/Funding (institution): Kyorin; Advisory/Consultancy: Celltrion; Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Nippon Kayaku; Honoraria (institution), Research grant/Funding (institution): Eli Lilly; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bayer; Honoraria (self): Kyowa Hakko Kirin; Research grant/Funding (institution): Dainippon- Sumitomo; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Kissei; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Loxo; Honoraria (self): MSD. All other authors have declared no conflicts of interest.