Comprehensive biomarker analysis from phase II study of nivolumab in patients with thymic carcinoma.

In a phase II trial of nivolumab in advanced thymic carcinoma (UMIN000022007), long SD (SD for more than 24 weeks) was seen in three patients and irAE (Gr2 or higher) was seen in four patients among 15 patients. Here, we report preplanned comprehensive biomarker analyses. We obtained tumor samples for immunohistochemistry, peripheral blood mononuclear cells (PBMCs), plasma and serum for pharmacokinetic analysis of nivolumab and cytokine evaluations, and whole blood for immuno pharmacogenomic (PGx) analysis. PD-L1 expression on tumor cells were not associated with therapeutic efficacy, but FOXP3 expression in tumor area and stroma, CD204 expression in stroma, and MHC class I in tumor area were all low among long SD patients. PBMC of long SD patients presented with larger number of naïve/memory cells prior to treatment, suggesting priming after nivolumab administration. Immuno-PGx analysis showed non-synonymous SNVs in

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Copyright © 2023 Katsuya, Kitano, Yamashita, Ouchi, Yagishita, Hamada, Nakamura, Hosoda, Shibata, Motoi, Nakayama, Seto, Umemura, Hosomi, Satouchi, Nishio, Kozuki, Hida, Ohe and Horinouchi.

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SK reports grants and personal fees from Astra Zeneca, grants and personal fees from Pfizer, grants and personal fees from Boehringer Ingelheim, personal fees from Taiho, personal fees from Novartis, grants and personal fees from MSD, personal fees from Sumitomo Dainippon Pharma, grants and personal fees from Eisai, grants from Astellas, grants from Gilead Sciences, grants and personal fees from Ono Pharmaceutical Co., Ltd., personal fees from Bristol-Myers Squibb, grants and personal fees from REGENERON, personal fees from Rakuten Medical, grants from PACT Pharma, grants from Takara Bio Inc., personal fees from GSK, grants and personal fees from Daiichi-Sankyo, grants and personal fees from Chugai, personal fees from ImmuniT Research Inc., grants from AMED(Japan Agency for Medical Research and Development), grants from JSPS(Japan Society for the Promotion of Science), personal fees from PMDA(Pharmaceuticals and Medical Devices Agency), outside the submitted work. SY reports grants from Nippon Boheringer Ingelheim, outside the submitted work. AH reports Grants or contracts from Eisai, Healios, Eli Lilly, Daiichi Sankyo, Chordia Therapeutics, Konica Minolta, outside the submitted work. TSe reports Grants or contracts from Abbvie, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, MSD, Novartis Pharma. Pfizer Japan, Takeda Pharmaceutical, and Payment of honoraria from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Covidien Japan, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, MSD, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical, Towa Pharmaceutical, and other interests from Precision Medicine Asia, outside the submitted work. SU reports Payment of honoraria from Chugai Pharmaceutical, outside the submitted work. YH reports Payment of honoraria from AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Eisai, outside the submitted work. MS reports Grants or contracts from Ono, Bristol Myers Squibb, Chugai, MSD, IQVIA, EPS, Janssen, Amgen, Taiho, Pfizer, Abbvie, Daiichi-Sankyo, Takeda, Eisai, and Payment of honoraria from Ono, Bristol Myers Squibb, Chugai, MSD, AstraZeneca, Eli Lilly, Taiho, Pfizer, Novartis, Takeda, Merck, outside the submitted work. MN reports grants and personal fees from Ono Pharmaceutical, grants and personal fees from Bristol Myers Squibb, grants and personal fees from Pfizer, grants and personal fees from Chugai Pharmaceutical, grants and personal fees from Eli Lilly, grants and personal fees from Taiho Pharmaceutical, grants and personal fees from AstraZeneca, personal fees from Boehringer-Ingelheim, grants and personal fees from MSD, grants and personal fees from Novartis, personal fees from Merck Biopharma, grants and personal fees from Daiichi Sankyo, grants and personal fees from Takeda Pharmaceutical Company Limited, personal fees from Teijin Pharma Limited., personal fees from AbbVie, outside the submitted work. TK reports Consulting fees from Chugai Pharmaceutical Co., AstraZeneca, Ono Pharmaceutical Co., Pfizer Japan, Daiichi-Sankyo, Bayer, Abbvie, and Payment of honoraria from Chugai Pharmaceutical Co., AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical Co., Bristol-Myers Squibb, Ono Pharmaceutical Co., MSD, Pfizer Japan, Kyowa Hakko Kirin, Nippon Beohringer Ingelheim, Merck Biophama, Nippon Kayaku, Novartis, Daiichi-Sankyo, Takeda Pharmaceutical Co., Bayer, Sawai, outside the submitted work. TH reports Payment or honoraria from ONO Pharmaceutical, Bristol-Meyers Squibb, MSD, outside the submitted work. YO is an editorial board member, and reports Grants or contracts from AstraZeneca, Chugai, Lilly, ONO, BMS, Kyorin, Dainippon- Sumitomo, Pfizer, Taiho, Novartis, Takeda, Kissei, Daiichi-Sankyo, Janssen, LOXO, and Payment or honoraria from AstraZeneca, Chugai, Eli Lilly, ONO, BMS,Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho, Nippon Kayaku, Kyowa Hakko Kirin, and Payment for expert testimony from AstraZeneca, Chugai, ONO, BMS, Kyorin, Celltrion, Amgen, Nippon Kayaku, Boehringer Ingelheim, AnHeart Therapeutics Inc., and Leadership or fiduciary role in JSMO, JLCS, JCOG, outside the submitted work. HH reports Grants or contracts from MSD, Abbvie, AstraZeneca, BMS, Ono, Merck Biophama, Daiichi-Sankyo, Janssen, Genomic Helath, Chugai, Roche, and Novartis, and Payments or honoraria from AstraZeneca, MSD, Eli Lilly, Ono, BMS, Chugai, Roche, Kyowa-Kirin, and Novartis, and Participation on an Advisory board for AstraZeneca, Eli Lilly, Chugai, Roche, ONO, BMS, and MSD, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.