Abstract 1898P
Background
We report the results of a single-arm, prospective, non-randomized, non-comparative, open label, multicenter, phase II trial designed to assess the activity and safety of cisplatin, pemetrexed, and nivolumab as first line therapy in MPM. This trial has been registered as UMIN000030892.
Methods
Enrollment criteria were as follows: patients older than 20 years with pathologically confirmed, untreated, unresectable MPM, with measurable lesions and an Eastern Cooperative Oncology Group performance status (PS) of 0-1. The primary endpoint is the centrally reviewed objective response rate (ORR). The secondary endpoints include 1) response rate assessed by investigators, 2) disease control rate, 3) OS, 4) progression-free survival (PFS), 5) duration of response, and 6) time to response. Safety and adverse events will also be evaluated. Treatment is composed of two sequential phases: the combination phase and the maintenance phase. In the former, cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and nivolumab (360 mg/body) were administered intravenously. This treatment will be repeated every 3 weeks with a total of 4 to 6 cycles. If patients did not progress during the combination phase, maintenance therapy with nivolumab was administered until disease progression, unacceptable toxicities, or the patient’s condition met the withdrawal criteria. Tissue samples were required and collected for programmed death ligand (PD-L) 1 analysis.
Results
We recruited 18 participants from Jan 2018 to May 2018. Median age was 69 (range 64-78), female/male was 3/15, PS 0/1 was 3/15, and epithelioid/biphasic/sarcomatoid histology was 14/2/2. Clinical stage IA/IB/IIA/IIB/IIIA/IIIB/IV was 2/6/0/0/9/1 and PD-L1 expression <1%/1-49%/≧50% was 1/12/5. The ORR rate was 77.8% (95% C.I. 53.9 – 91.5%) according to modified RECIST criteria. The median PFS and OS were 8.0 and 20.8 months, respectively. Grade 3-4 adverse events occurred in 10 participants. There was no death related to the treatment.
Conclusions
The combination of cisplatin, pemetrexed, and nivolumab has demonstrated sufficient activity and safety as first line therapy in MPM.
Clinical trial identification
UMIN000030892.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This study is granted by Ono Pharmaceutical Co., Ltd. and also by grants-in-aid from the Ministry of Health, Labor, and Welfare, Japan.
Disclosure
N. Fujimoto: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): ONO; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Kissei; Research grant/Funding (institution): MSD; Honoraria (self): Chugai; Honoraria (self): Daiichi Sankyo. T. Kozuki: Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Eli Lilly Japan; Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Merck Biopharma; Honoraria (self): Ono; Honoraria (self): MSD; Honoraria (self): Pfizer Japan; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): Nippon Kayaku; Honoraria (self): Novartis. D. Harada: Honoraria (self), Research grant/Funding (institution): Ono; Honoraria (self), Research grant/Funding (institution): Eli Lilly Japan; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Pfizer japan; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Kissei; Research grant/Funding (institution): Takeda; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Taiho; Honoraria (self): Nippon Boehringer Ingelheim. K. Hotta: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): MSD; Research grant/Funding (institution): Chugai; Research grant/Funding (institution): Eli Lilly Japan; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Astellas. All other authors have declared no conflicts of interest.