TY - JOUR
T1 - Safety and antitumor activity of copanlisib in Japanese patients with relapsed/refractory indolent non-Hodgkin lymphoma
T2 - a phase Ib/II study
AU - Fukuhara, Noriko
AU - Maruyama, Dai
AU - Hatake, Kiyohiko
AU - Nagai, Hirokazu
AU - Makita, Shinichi
AU - Kamezaki, Kenjiro
AU - Uchida, Toshiki
AU - Kusumoto, Shigeru
AU - Kuroda, Junya
AU - Iriyama, Chisako
AU - Yanada, Masamitsu
AU - Tsukamoto, Norifumi
AU - Suehiro, Youko
AU - Minami, Hironobu
AU - Garcia-Vargas, Jose
AU - Childs, Barrett H.
AU - Yasuda, Masanobu
AU - Masuda, Shigeo
AU - Tsujino, Toshiaki
AU - Terao, Yui
AU - Tobinai, Kensei
N1 - Funding Information:
Noriko Fukuhara has received research grants from AbbVie, Bayer, Eisai, Gilead Sciences, Ono Pharmaceutical, and Solasia Pharma and honoraria from Chugai and Kyowa Kirin. Dai Maruyama has received research grants from Celgene, Novartis, Chugai, Ono Pharmaceutical, Takeda, Janssen, and MSD and honoraria from Janssen, Mundipharma, Eisai, and Chugai. Kiyohiko Hatake has received honoraria/lecture fees from Takeda, Chugai, Celgene, Otsuka, Towa, Kyowa Kirin, Daiichi Sankyo, Eisai, Yakult Honsha, and Meiji Seika Pharma and consulting fees from Eisai. Hirokazu Nagai has received research grants from AstraZeneca, Celgene, Mundipharma, Zenyaku Kogyo, Takeda, Chugai, Bayer, Bristol Myers Squibb, Janssen, Kyowa Kirin, Ono Pharmaceutical, MSD, and SymBio Pharmaceuticals and honoraria/lecture fees from Eisai, Chugai, Takeda, Celgene, Mundipharma, Kyowa Kirin, Ono Pharmaceutical, AstraZeneca, Sanofi, Bristol Myers Squibb, Novartis, Janssen, SymBio Pharmaceuticals, Chordia Therapeutics, and Nihon Medi-Physics. Shinichi Makita has received honoraria from Celgene, Bristol Myers Squibb, Chugai, CSL Behring, Daiichi Sankyo, Eisai, Novartis, SymBio Pharmaceuticals, and Takeda and advisory board fees from Takeda, Celgene, Bristol Myers Squibb, Daiichi Sankyo, and Novartis. Shigeru Kusumoto has received research grants from Chugai, Daiichi Sankyo, Kyowa Kirin, Janssen, Bristol Myers Squibb, and Bayer and honoraria/lecture fees from Chugai, Daiichi Sankyo, Kyowa Kirin, Janssen, and Bristol Myers Squibb. Junya Kuroda has received research grants from Kyowa Kirin, Chugai, Ono Pharmaceutical, Sanofi, Eisai, Bristol Myers Squibb, Sysmex, Sumitomo Dainippon Pharma, Nippon Shinyaku, AbbVie, Teijin, and Otsuka Pharmaceutical; honoraria from Janssen K.K., Kyowa Kirin, Chugai, Ono Pharmaceutical, Sanofi, Eisai, SymBio, Bristol Myers Squibb, Astellas Pharma, Pfizer, Nippon Shinyaku, Daiichi Sankyo, Sumitomo Dainippon Pharma, AbbVie, Novartis, and Otsuka Pharmaceutical; and consultant fees from Janssen K.K. and Bristol Myers Squibb. Masamitsu Yanada has received research grants from AbbVie, AstraZeneca, Bayer, Celgene, Chugai, Eisai, IQVIA, Genmab, Incyte, Mundipharma, Novartis, Ono Pharmaceutical, Otsuka Pharmaceutical, Solasia Pharma, SymBio, Takeda, Yakult, and Zenyaku Kogyo. Youko Suehiro has received research grants from Chugai, Genmab, Kyowa Kirin, Incyte, Amgen, Ono Pharmaceutical, Otsuka Pharmaceutical, and Teijin and honoraria from Chugai, Ono Pharmaceutical, Takeda, Eisai, Kyowa Kirin, Celgene, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Bristol Myers Squibb, AbbVie, Meiji Seika Pharma, Pfizer, and Sanofi. Hironobu Minami has received research grants from Asahi Kasei Pharma, Astellas, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, CSL Behring, Daiichi Sankyo, Sumitomo Dainippon Pharma, Eisai, Kyowa Kirin, Lilly, Merck Serono, Mitsubishi Tanabe, MSD, Nippon Kayaku, Nippon Shinyaku, Ono Pharmaceutical, Otsuka Pharmaceutical, Sanofi, Shionogi, Takeda, Taiho, Teijin, and Tsumura; honoraria from AbbVie, Bayer, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Sumitomo Dainippon Pharma, Eisai, Genomic Health, Kyowa Kirin, Lilly, Meiji Seika Pharma, Merck Serono, MSD, Nihon Servier, Novartis, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Sanofi, Taiho, and Takeda; and grants for clinical trials from AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Daiichi Sankyo, MSD, Ono Pharmaceutical, Pfizer, Taiho, Amgen, Novartis, and Insight Bioscience Japan. Jose Garcia-Vargas and Barrett H. Childs are employees of Bayer Healthcare Pharmaceuticals Inc. Masanobu Yasuda, Shigeo Masuda, Toshiaki Tsujino, and Yui Terao are employees of Bayer Yakuhin Ltd. Kenjiro Kamezaki, Toshiki Uchida, Chisako Iriyama, and Norifumi Tsukamoto declare no conflict of interest. Kensei Tobinai has received honoraria from Zenyaku Kogyo and HUYA Bioscience.
Funding Information:
We would like to thank Catherine Rees and Mitali Choudhury of inScience Communications, Springer Healthcare who wrote the outline and the subsequent drafts of this manuscript, respectively. This medical writing assistance was funded by Bayer Yakuhin, Ltd.
Publisher Copyright:
© 2022, The Author(s).
PY - 2023/1
Y1 - 2023/1
N2 - The safety, efficacy, and pharmacokinetics of copanlisib were evaluated in this phase Ib/II study in Japanese patients with relapsed/refractory indolent non-Hodgkin lymphoma (NHL). The primary endpoint was safety at the recommended dose; efficacy endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival. In phase Ib, patients received copanlisib 45 mg intravenously on days 1, 8, and 15 of a 28-day cycle, and when tolerated, consecutive patients received copanlisib 60 mg. As no dose-limiting toxicities occurred at the 45 mg (n = 3) or 60 mg (n = 7) dose in phase Ib, the recommended dose for Japanese patients was determined to be 60 mg, and this dose was used in phase II (n = 15). Although all patients experienced at least one treatment-emergent adverse event (TEAE), with hyperglycemia being the most common AE, no AE-related deaths were reported. The ORR was 68.0% (17/25 patients), median PFS was 302 (95% CI 231–484) days, and the duration of response was 330 (range 65–659) days. The pharmacokinetic properties of copanlisib were similar between Japanese and non-Japanese patients. Overall, copanlisib 60 mg had an acceptable safety profile and showed promising antitumor activity in Japanese patients with relapsed/refractory indolent NHL.
AB - The safety, efficacy, and pharmacokinetics of copanlisib were evaluated in this phase Ib/II study in Japanese patients with relapsed/refractory indolent non-Hodgkin lymphoma (NHL). The primary endpoint was safety at the recommended dose; efficacy endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival. In phase Ib, patients received copanlisib 45 mg intravenously on days 1, 8, and 15 of a 28-day cycle, and when tolerated, consecutive patients received copanlisib 60 mg. As no dose-limiting toxicities occurred at the 45 mg (n = 3) or 60 mg (n = 7) dose in phase Ib, the recommended dose for Japanese patients was determined to be 60 mg, and this dose was used in phase II (n = 15). Although all patients experienced at least one treatment-emergent adverse event (TEAE), with hyperglycemia being the most common AE, no AE-related deaths were reported. The ORR was 68.0% (17/25 patients), median PFS was 302 (95% CI 231–484) days, and the duration of response was 330 (range 65–659) days. The pharmacokinetic properties of copanlisib were similar between Japanese and non-Japanese patients. Overall, copanlisib 60 mg had an acceptable safety profile and showed promising antitumor activity in Japanese patients with relapsed/refractory indolent NHL.
UR - http://www.scopus.com/inward/record.url?scp=85139187850&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85139187850&partnerID=8YFLogxK
U2 - 10.1007/s12185-022-03455-0
DO - 10.1007/s12185-022-03455-0
M3 - Article
C2 - 36175779
AN - SCOPUS:85139187850
VL - 117
SP - 100
EP - 109
JO - International Journal of Hematology
JF - International Journal of Hematology
SN - 0925-5710
IS - 1
ER -