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Yuko Tsuchiya-Kawano,1 Yoshimasa Shiraishi,2 Fumiaki Kiyomi,3 Isamu Okamoto2 1Department of Respiratory Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 3Statistics and Data Center, Clinical Research Support Center Kyushu, Fukuoka, JapanCorrespondence: Isamu OkamotoResearch Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, JapanTel +81-92-642-5378Fax +81-92-642-5390Email okamoto.isamu.290@m.kyushu-u.ac.jpAbstract: The standard of care for advanced non-small cell lung cancer (NSCLC) without known driver oncogenes is immune checkpoint inhibitor (ICI) therapy combined with platinum-based chemotherapy. About 20% of patients with advanced NSCLC have brain metastases, which are related to poor prognosis. However, the effect of ICI therapy combined with platinum-based chemotherapy on untreated brain metastases derived from NSCLC remains unclear. The primary endpoint of this study is intracranial response rate as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST) for brain metastases of ≥ 5 mm as target lesions. Eligible patients are 20 years of age or older with chemotherapy-naïve advanced NSCLC and at least one brain metastasis ≥ 5 mm in size that has not been previously treated. Patients receive nivolumab plus ipilimumab intravenously combined with histology-based platinum doublet chemotherapy (two cycles). Individuals with known genetic driver alterations such as those affecting EGFR or ALK are excluded. Planned enrollment is 30 patients over 2.5 years at 27 oncology facilities in Japan. This is the first prospective study to focus on the intracranial response to ICI therapy combined with platinum-based chemotherapy in patients with untreated brain metastases derived from NSCLC. If the study demonstrates intracranial efficacy for this patient population, then this regimen has the potential to become a new treatment option for such individuals.Keywords: clinical trial, NSCLC, nivolumab plus ipilimumab, brain metastases, intracranial response rate

Hideki Miyake,1 Yuri Kawano,2 Hiroshi Tanaka,2 Akihiro Iwata,3 Takahiro Imanaka,1 Masatsugu Nakamura1 1Ophthalmic Disease Area Strategy Department, 2Clinical Operations Department, 3Data Science Department, R&D Division, Santen Pharmaceutical Co., Ltd. Osaka, Japan Purpose: We aimed to evaluate the feasibility of using a modified Schirmer test to determine the increase in tear volume after administration of 3% diquafosol ophthalmic solution (diquafosol 3%) in dry eye patients. Patients and methods: A randomized, multicenter, prospective, double-blind clinical study recruited 50 qualified subjects. They received diquafosol 3% in one eye and artificial tears in the other eye. The study protocol comprised a screening and treatment procedure completed within 1 day. The Schirmer test was performed on closed eyes three times a day. The primary efficacy end points were the second Schirmer test scores 10 minutes after the single dose. Secondary end points were the third Schirmer test scores 3 hours and 40 minutes after the single dose and the symptom scores prior to the second and third Schirmer tests. Results: According to the Schirmer test, 10 minutes after administration, diquafosol 3% significantly increased tear volume compared to artificial tears. Diquafosol 3% and artificial tears both showed significant improvements in the symptom scores compared to baseline. However, there was no significant difference in the symptoms score between diquafosol 3% and artificial tears. Conclusion: The modified Schirmer test can detect a minute change in tear volume in dry eye patients. These findings will be useful in the diagnosis of dry eye, assessment of treatment benefits in daily clinical practice, and the development of possible tear-secreting compounds for dry eye. Keywords: P2Y2, efficacy, Diquas®